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  • 1.
    Abdeldaim, Guma M. K.
    et al.
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Clinical Mycobacteriology, National Center for Diseases Control, Benghazi, Libyan Arab Jamahiriya.
    Strålin, Kristoffer
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Olcén, Per
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Blomberg, Jonas
    Section of Clinical Virology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine.
    Herrmann, Björn
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia2013In: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 76, no 2, p. 141-146Article in journal (Refereed)
    Abstract [en]

    A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions.

  • 2.
    Abdurahman, Samir
    et al.
    Division of Clinical Microbiology, Karolinska Institutet, F68 Karolinska University Hospital Huddinge, Stockholm, Sweden .
    Végvári, Akos
    Clinical Protein Science, Department of Electrical Measurements, Lund University, Lund, Sweden.
    Youssefi, Masoud
    Division of Clinical Microbiology, Karolinska Institutet, F68 Karolinska University Hospital Huddinge, Stockholm, Sweden .
    Levi, Michael
    Tripep AB, Huddinge, Sweden .
    Höglund, Stefan
    Department of Biochemistry, Uppsala University, Uppsala, Sweden .
    Andersson, Elin
    Department of Clinical Virology, University of Göteborg, Göteborg, Sweden.
    Horal, Peter
    Department of Clinical Virology, University of Göteborg, Göteborg, Sweden.
    Svennerholm, Bo
    Department of Clinical Virology, University of Göteborg, Göteborg, Sweden.
    Balzarini, Jan
    Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
    Vahlne, Anders
    Division of Clinical Microbiology, Karolinska Institutet, F68 Karolinska University Hospital Huddinge, Stockholm, Sweden .
    Activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity2008In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 10, p. 3737-3744Article in journal (Refereed)
    Abstract [en]

    Upon maturation of the human immunodeficiency virus type 1 (HIV-1) virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. We have reported earlier that glycineamide (G-NH(2)), when added to the culture medium of infected cells, inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH(2) itself but a metabolite thereof, alpha-hydroxy-glycineamide (alpha-HGA), that is responsible for the antiviral activity. We show that alpha-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of 10 different RNA and DNA viruses. alpha-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by matrix-assisted laser desorption ionization-mass spectrometry results. As an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances.

  • 3.
    Afshar, Mastaneh
    et al.
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Poehlein, Anja
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Brüggemann, Holger
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Complete Genome Sequences of Two Staphylococcus saccharolyticus Strains Isolated from Prosthetic Joint Infections2021In: Microbiology Resource Announcements, E-ISSN 2576-098X, Vol. 10, no 10, article id e00157-21Article in journal (Refereed)
    Abstract [en]

    Staphylococcus saccharolyticus is a human skin bacterium and is occasionally associated with prosthetic joint infections (PJIs). Here, we report the complete genome sequences of two strains that were isolated from shoulder and hip PJIs. The genomes show signs of reductive evolution; around 21% of all coding sequences are inactivated by frameshift mutations.

  • 4.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Hematology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Örebro University Hospital. Department of Infectious diseases, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious diseases & Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, p. 539-544Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  • 5.
    Ajab, Suad
    et al.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
    Zoughbor, Sumaya
    Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
    Labania, Lena
    Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
    Olanda, Marie
    Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
    Östlundh, Linda
    National Medical Library, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
    Al Rasbi, Zakeya
    Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
    The role of microbiota in immunotherapy outcomes in colorectal cancer patients: A protocol for a systematic review2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 8, article id e0273314Article, review/survey (Refereed)
    Abstract [en]

    In the human gut, there are many microbes, including bacteria, viruses and parasites. The imbalance in the numbers of each type of these microbes can translate into gastrointestinal disorders. Lately, different microbiota patterns have been associated with the levels of efficacy of immunotherapy in multiple cancer conditions. Studies have shown that patients with a more diverse gut microbiome respond better to immunotherapy than those with a homogeneous microbiome. This systematic review aims to identify and assess the available evidence on the efficacy of immunotherapy in treating colorectal cancer (CRC) patients and the effect of their microbiota on their treatment outcomes. The researchers will study the literature regarding CRC and immunotherapy outcomes to survey the different approaches employed to assess the treatment outcomes. A systematic search will be performed in five biomedical databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Library) in June-July, 2022. Also, open-access registers of clinical trials will be trawled. The search will be conducted without geographical or publication date restrictions; however, only papers published in the English language will be sought. Details regarding patients' diets, lifestyles, and characteristics will be assessed. We will define the primary outcome to compare CRC patients' immunotherapy responses with their gut microbiota composition. The systematic review methodology does not require ethics approval due to the nature of the study design. The systematic review results will be published in an open-access peer-reviewed journal.

    PROSPERO ID: CRD42021277691.

  • 6.
    Al Janabi, Jasmina
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tevell, Staffan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Karlstad Hospital and Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden.
    Sieber, Raphael Niklaus
    Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Stegger, Marc
    Örebro University, School of Medical Sciences. Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Emerging resistance in Staphylococcus epidermidis during dalbavancin exposure: a case report and in vitro analysis of isolates from prosthetic joint infections2023In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 78, no 3, p. 669-677Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dalbavancin, a semisynthetic lipoglycopeptide with exceptionally long half-life and Gram-positive spectrum, is an attractive option for infections requiring prolonged therapy, including prosthetic joint infections (PJIs).

    OBJECTIVES: To investigate the prevalence of reduced susceptibility to dalbavancin in a strain collection of Staphylococcus epidermidis from PJIs, and to investigate genomic variation in isolates with reduced susceptibility selected during growth under dalbavancin exposure.

    METHODS: MIC determination was performed on S. epidermidis isolates from a strain collection (n = 64) and from one patient with emerging resistance during treatment (n = 4). These isolates were subsequently cultured on dalbavancin-containing agar and evaluated at 48 h; MIC determination was repeated if phenotypical heterogeneity was detected during growth. Population analysis profile (PAP-AUC) was performed in isolates where a  ≥ 2-fold increase in MIC was detected, together with corresponding parental isolates (n = 21). Finally, WGS was performed.

    RESULTS: All strains grew at 48 h on agar containing 0.125 mg/L dalbavancin. PAP-AUC demonstrated significant differences between parental and derived strains in four of the eight analysed groups. An amino acid change in the walK gene coinciding with emergence of phenotypic resistance was detected in the patient isolates, whereas no alterations were found in this region in the in vitro derived strains.

    CONCLUSIONS: Exposure to dalbavancin may lead to reduced susceptibility to dalbavancin through either selection of pre-existing subpopulations, epigenetic changes or spontaneous mutations during antibiotic exposure. Source control combined with adequate antibiotic concentrations may be important to prevent emerging reduced susceptibility during dalbavancin treatment.

  • 7.
    Alim, Abdul
    et al.
    Örebro University, School of Medical Sciences. Oru.
    Pelli, F.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Asghar, Naveed
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Tick-borne encephalitis virus protein expression to develop novel subunit vaccines and diagnostic tools2023Conference paper (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV) and Langat virus (LGTV) are both members of Flavivirus genus within the Flaviviridae family. TBEV is the main pathogenic arbovirus circulating in Europe, Russia, and China. Flaviviruses are characterized by a positive sense single-stranded RNA genome and an enveloped icosahedral virion structure. Previously, it has been observed that flavivirus envelope (E) protein and non-structural protein 1 (NS1) both play a critical role in the pathology of flavivirus. Therefore, in this study, we aim to investigate flavivirus E and NS1 protein as a good target for the development of a subunit vaccine with further potential as a putative diagnostic tool to distinguish between TBEV infected from TBEV vaccinated individuals. Thus, we have generated 4 different successful constructs with TBEV (E and NS1) and LGTV (E and NS1) in the pET SUMO vector. Restriction digestion and sequencing analysis confirmed successful clones of interest and their right orientation. Next, the right clones were transformed in BL21 (DE3) one shoot chemically competent E. coli and induce the expression with 0.5 mM IPTG in culture medium following 0-4h, and 24h incubation period. Next, bacterial cell pellets were collected and used for SDSPAGE/Western blot analysis. We used the champion™ pET SUMO expression system which may produce high levels of soluble protein in bacteria. It employs a small ubiquitin-related modifier (SUMO) fusion, belonging to the growing family of ubiquitin-related proteins, to enhance the solubility of expressed fusion proteins. We have stained with 6x-His tag antibody of interest (mouse monoclonal) for targeting both TBEV- E/NS1 and LGTV-E/NS1 proteins. Among them, the expression of TBEV-NS1 and LGTV-E proteins was verified and confirmed. Several attempts have also been made to obtain the TBEV-E and LGTV-NS1 protein in E. coli cells; however, these require further optimization with a suitable time and dose of IPTG induction. We have used the BL21(DE3) expression system, which could maximize the expression of soluble protein. After successful expression, the 13-kd SUMO moiety will be cleaved by the highly specific and active SUMO (ULP1) protease at the carboxyl terminal, producing a native protein. Furthermore, a protein purification assay (e-g., NI-NTA column/ÄKTA Protein Purification Systems) will be developed to obtain native recombinant protein. The purified proteins will be studied in combination with suitable adjuvants as putative TBE subunit vaccines. They will also be characterized with the potential to develop new tools for TBE diagnostics. 

    Download (pdf)
    Summary
  • 8.
    Alpkvist, Helena
    et al.
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Naucler, Pontus
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Herrmann, Björn
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Abdeldaim, Guma
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Medical Microbiology and Parasitology, Faculty of Medicine, Benghazi University, Benghazi, Libya.
    Slotved, Hans-Christian
    Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Hedlund, Jonas
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 10, article id e0140112Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.

    Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.

    Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.

    Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

  • 9. Amoudruz, Petra
    et al.
    Holmlund, Ulrika
    Schollin, Jens
    Örebro University, School of Health and Medical Sciences.
    Sverremark-Ekström, Eva
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Maternal country of birth and previous pregnancies are associated with breast milk characteristics2009In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 20, no 1, p. 19-29Article in journal (Refereed)
    Abstract [en]

    Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

  • 10.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    CHIMERIC MOMP ANTIGEN2015Patent (Other (popular science, discussion, etc.))
    Download full text (pdf)
    Patent
  • 11.
    Anjum, Muna F
    et al.
    Department of Bacteriology, Animal and Plant Health Agency, Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
    Schmitt, Heike
    Centre for Zoonoses and Environmental Microbiology - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands.
    Börjesson, Stefan
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden; Department of Microbiology, Public Health Agency of Sweden, 171 82 Solna, Sweden.
    Berendonk, Thomas U
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden Present address: Department of Microbiology, Public Health Agency of Sweden, 171 82 Solna, Sweden.
    The potential of using E. coli as an indicator for the surveillance of antimicrobial resistance (AMR) in the environment2021In: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 64, p. 152-158Article, review/survey (Refereed)
    Abstract [en]

    To understand the dynamics of antimicrobial resistance (AMR), in a One-Health perspective, surveillance play an important role. Monitoring systems already exist in the human health and livestock sectors, but there are no environmental monitoring programs. Therefore there is an urgent need to initiate environmental AMR monitoring programs nationally and globally, which will complement existing systems in different sectors. However, environmental programs should not only identify anthropogenic influences and levels of AMR, but they should also allow for identification of transmissions to and from human and animal populations. In the current review we therefore propose using antimicrobial resistant Escherichia coli as indicators for monitoring occurrence and levels of AMR in the environment, including wildlife.

  • 12.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Sahdo, Berolla
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Balcha, Ermias
    Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Swedenital, Örebro, Sweden.
    Kelly, Anne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    C10X polymorphism in the CARD8 gene is associated with bacteraemia2014In: Immunity, inflammation and disease, E-ISSN 2050-4527, Vol. 2, no 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.

  • 13.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Paulsen, Katrine M.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Pedersen, Benedikte N.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Bø-Granquist, Erik G.
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Vikse, Rose
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Stuen, Snorre
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Andersson, Sören
    Folkhälsomyndigheten, Public Health Agency of Sweden, Solna, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andreassen, Åshild K.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Transient Expression of Flavivirus Structural Proteins in Nicotiana benthamiana 2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 10, article id 1667Article in journal (Refereed)
    Abstract [en]

    Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment availa-ble, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural pro-teins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection. 

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  • 14.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences. School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden; iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Pettersson, John H-O
    Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, Oslo, Norway; Department of Microbiology, National Veterinary Institute, Uppsala, Sweden; Department of Medical Biochemistry and Microbiology (IMBIM), Zoonosis Science Center, Uppsala University, Uppsala, Sweden.
    Dinnetz, Patrik
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Andreassen, Åshild
    Department of Virology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Deep sequencing analysis of tick-borne encephalitis virus from questing ticks at natural foci reveals similarities between quasispecies pools of the virus2017In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 98, no 3, p. 413-421Article in journal (Refereed)
    Abstract [en]

    Every year, tick-borne encephalitis virus (TBEV) causes severe central nervous system infection in 10,000 to 15,000 people in Europe and Asia. TBEV is maintained in the environment by an enzootic cycle that requires a tick vector and a vertebrate host, and the adaptation of TBEV to vertebrate and invertebrate environments is essential for TBEV persistence in nature. This adaptation is facilitated by the error-prone nature of the virus' RNA-dependent RNA polymerase that generates genetically distinct virus variants called quasispecies. TBEV shows a focal geographical distribution pattern where each focus represents a TBEV hotspot. Here we sequenced and characterized two TBEV genomes, JP-296 and JP-554, from questing Ixodes ricinus ticks at a TBEV focus in central Sweden. Phylogenetic analysis showed geographical clustering among the newly sequenced strains and three previously sequenced Scandinavian strains, Toro-2003, Saringe-2009, and Mandal-2009, which originated from same ancestor. Among these five Scandinavian TBEV strains, only Mandal-2009 showed a large deletion within the 3´ non-coding region (NCR) similar to the highly virulent TBEV strain Hypr. Deep sequencing of JP-296, JP-554, and Mandal-2009 revealed significantly high quasispecies diversity for JP-296 and JP-554, with intact 3´NCRs, compared to the low diversity in Mandal-2009, with a truncated 3´NCR. SNP analysis showed that 40% of the SNPs were common between quasispecies populations of JP-296 and JP-554, indicating a putative mechanism for how TBEV persists and is maintained within its natural foci.

  • 15. Aspholm, Marina
    et al.
    Kalia, Awdhesh
    Ruhl, Stefan
    Schedin, Staffan
    Arnqvist, Anna
    Lindén, Sara
    Sjöström, Rolf
    Gerhard, Markus
    Semino-Mora, Cristina
    Dubois, Andre
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Danielsson, Dan
    Teneberg, Susann
    Lee, Woo-Kon
    Berg, Douglas E.
    Borén, Thomas
    Helicobacter pylori adhesion to carbohydrates2006In: Methods in Enzymology, ISSN 0076-6879, E-ISSN 1557-7988, Vol. 417, p. 293-339Article in journal (Refereed)
    Abstract [en]

    Adherence of bacterial pathogens to host tissues contributes to colonization and virulence and typically involves specific interactions between bacterial proteins called adhesins and cognate oligosaccharide (glycan) or protein motifs in the host that are used as receptors. A given pathogen may have multiple adhesins, each specific for a different set of receptors and, potentially, with different roles in infection and disease. This chapter provides strategies for identifying and analyzing host glycan receptors and the bacterial adhesins that exploit them as receptors, with particular reference to adherence of the gastric pathogen Helicobacter pylori.

  • 16.
    Athlin, Simon
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Detection of polysaccharides and polysaccharide antibodies in pneumococcal pneumonia2015Doctoral thesis, comprehensive summary (Other academic)
    List of papers
    1. The Uni-Gold™ Streptococcus pneumoniae urinary antigen test: an inter-assay comparison with the BinaxNOW® Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremia
    Open this publication in new window or tab >>The Uni-Gold™ Streptococcus pneumoniae urinary antigen test: an inter-assay comparison with the BinaxNOW® Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremia
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-44401 (URN)
    Available from: 2015-04-22 Created: 2015-04-22 Last updated: 2019-04-24Bibliographically approved
    2. The Binax NOW Streptococcus pneumoniae test applied on nasopharyngeal aspirates to support pneumococcal aetiology in community-acquired pneumonia.
    Open this publication in new window or tab >>The Binax NOW Streptococcus pneumoniae test applied on nasopharyngeal aspirates to support pneumococcal aetiology in community-acquired pneumonia.
    2013 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 6, p. 425-31Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: The use of nasopharyngeal secretions to enhance diagnostic yields of pneumococcal aetiology in community-acquired pneumonia (CAP) is of interest. We evaluated the Binax NOW Streptococcus pneumoniae immunochromatographic test (ICT) on nasopharyngeal aspirates (NPA) in order to support pneumococcal aetiology in CAP.

    METHODS: The NPA ICT was applied on 180 adult CAP patients and 64 healthy controls. The rate of pneumococcal detection in the nasopharynx was compared to rates for lytA polymerase chain reaction (PCR) and culture on NPA.

    RESULTS: According to blood and sputum culture and urine ICT, the test sensitivity in 59 patients with a pneumococcal aetiology was 81%. The specificity was suboptimal, with 72% negative tests among CAP patients without a pneumococcal aetiology. However, the test was positive in only 11% of patients with atypical pneumonia and in 4.7% of healthy controls. The positivity rate was higher for NPA ICT compared to culture on NPA in all CAP patients, and to both PCR and culture on NPA in non-pneumococcal non-atypical CAP patients. In 113 (63%) patients with β-lactam monotherapy, cure without treatment alteration was noted more often in cases with positive compared to negative NPA ICT at admission (91% vs 69%; p < 0.01).

    CONCLUSIONS: The high sensitivity and the low positivity rates in patients with atypical pneumonia and healthy controls, in combination with the correlation between positive test results and clinical cure with β-lactam therapy, may support a pneumococcal aetiology in CAP in populations with low pneumococcal carriage rates.

    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-44372 (URN)10.3109/00365548.2012.760843 (DOI)000318940400002 ()23330980 (PubMedID)2-s2.0-84877917212 (Scopus ID)
    Note

    Funding Agency: Research Committee of Orebro County Council

    Available from: 2015-04-22 Created: 2015-04-20 Last updated: 2020-12-01Bibliographically approved
    3. Clinical and microbiological factors associated with high pneumococcal colonization density in pneumococcal pneumonia
    Open this publication in new window or tab >>Clinical and microbiological factors associated with high pneumococcal colonization density in pneumococcal pneumonia
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-44402 (URN)
    Available from: 2015-04-22 Created: 2015-04-22 Last updated: 2019-04-24Bibliographically approved
    4. Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential
    Open this publication in new window or tab >>Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential
    Show others...
    2014 (English)In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 11, p. 1541-1549Article in journal (Refereed) Published
    Abstract [en]

    We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.

    Place, publisher, year, edition, pages
    American Society for Microbiology, 2014
    National Category
    Infectious Medicine Immunology in the medical area
    Identifiers
    urn:nbn:se:oru:diva-44373 (URN)10.1128/CVI.00259-14 (DOI)000344651200011 ()25230937 (PubMedID)2-s2.0-84914697787 (Scopus ID)
    Note

    Funding Agency: Research Committee of Orebro County Council OLL-137011

    Available from: 2015-04-22 Created: 2015-04-20 Last updated: 2020-12-01Bibliographically approved
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  • 17.
    Atterby, Clara
    et al.
    Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Osbjer, Kristina
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden; Food and Agriculture Organization of the United Nations, Phnom Penh, Cambodia.
    Tepper, Viktoria
    Institute of Environmental Engineering, ETH Zürich, Switzerland.
    Rajala, Elisabeth
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
    Hernandez, Jorge
    Center for Ecology and Evolution in Microbial Model Systems Linnaeus University, Kalmar, Sweden; Department of Infectious Diseases, Kalmar County Council, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Diagnostic Centrum, Clinic Microbiologic Laboratory, Kalmar County Hospital, Kalmar, Sweden.
    Seng, Sokerya
    Food and Agriculture Organization of the United Nations, Phnom Penh, Cambodia.
    Holl, Davun
    General Directorate of Animal Health and Production, Ministry of Agriculture, Forestry and Fisheries, Phnom Penh, Cambodia.
    Bonnedahl, Jonas
    Center for Ecology and Evolution in Microbial Model Systems Linnaeus University, Kalmar, Sweden; Department of Infectious Diseases, Kalmar County Council, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Börjesson, Stefan
    Department of Animal Health and Antimicrobial strategies, National Veterinary Institute (SVA), Uppsala, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Magnusson, Ulf
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
    Järhult, Josef D
    Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Carriage of carbapenemase- and extended-spectrum cephalosporinase-producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia; gender and age differences and detection of blaOXA-48 in humans.2019In: Zoonoses and Public Health, ISSN 1863-1959, E-ISSN 1863-2378, Vol. 66, no 6, p. 603-617Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study investigates the frequency and characteristics of carbapenemase-producing Escherichia coli/Klebsiella pneumoniae (CPE/K) and extended-spectrum cephalosporinase-producing E. coli/K. pneumoniae (ESCE/K) in healthy humans and livestock in rural Cambodia. Additionally, household practices as risk factors for faecal carriage of ESCE/K are identified.

    METHODS: Faecal samples were obtained from 307 humans and 285 livestock including large ruminants, pigs and poultry living in 100 households in rural Cambodia in 2011. Each household was interviewed, and multilevel logistic model determined associations between household practices/meat consumption and faecal carriage of ESCE/K. CPE and ESCE/K were detected and further screened for colistin resistance genes.

    RESULTS: CPE/K isolates harbouring blaOXA-48 were identified in two humans. The community carriage of ESCE/K was 20% in humans and 23% in livestock. The same ESBL genes: blaCTX-M-15 , blaCTX-M-14 , blaCTX-M-27 , blaCTX-M-55 , blaSHV-2 , blaSHV-12 , blaSHV-28 ; AmpC genes: blaCMY-2 , blaCMY-42, blaDHA-1 ; and colistin resistance genes: mcr-1-like and mcr-3-like were detected in humans and livestock. ESCE/K was frequently detected in women, young children, pigs and poultry, which are groups in close contact. The practice of burning or burying meat waste and not collecting animal manure indoors and outdoors daily were identified as risk factors for faecal carriage of ESCE/K.

    CONCLUSIONS: Faecal carriage of E. coli and K. pneumoniae harbouring extended-spectrum cephalosporinase genes are common in the Cambodian community, especially in women and young children. Exposure to animal manure and slaughter products are risk factors for intestinal colonization of ESCE/K in humans.

  • 18.
    Bala, Manju
    et al.
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Singh, Vikram
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Philipova, Ivva
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden; National Reference Laboratory for Mycology and Sexually Transmitted Infections (STIs), National Center of Infections and Parasitic Diseases, Sofia, Bulgaria.
    Bhargava, Aradhana
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Chandra Joshi, Naveen
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 7, p. 1856-1859Article in journal (Refereed)
    Abstract [en]

    Objectives: XDR Neisseria gonorrhoeae imposes the threat of untreatable gonorrhoea. Gentamicin is considered for future treatment; however, no interpretation criteria for the CLSI and calibrated dichotomous sensitivity (CDS) disc diffusion (DD) techniques are available for N. gonorrhoeae. We investigated the in vitro gentamicin activity by MIC and DD methods, proposed DD breakpoints and determined DD ranges for 10 international quality control (QC) strains.

    Methods: Gentamicin susceptibility of 333 N. gonorrhoeae isolates, including 323 clinical isolates and 10 QC strains, was determined. MIC determination (Etest) and DD methods (CLSI and CDS) were performed. The relationship between MIC, inhibition zone diameter and annular radius was determined by linear regression analysis and the correlation coefficient (r) was calculated.

    Results: Gentamicin MICs for the QC strains were within published ranges. Of the 323 clinical isolates, according to published breakpoints 75.9%, 23.5% and 0.6% were susceptible, intermediately susceptible and resistant, respectively. Based on error minimization with MICs of ≤4, 8-16 and ≥32 mg/L, breakpoints proposed are susceptible ≥16 mm, intermediately susceptible 13-15 mm and resistant ≤12 mm for the CLSI method and susceptible ≥6 mm, less susceptible 3-5 mm and resistant ≤2 mm for the CDS technique.

    Conclusions: Low resistance to gentamicin was identified and gentamicin might be a future treatment option for gonorrhoea. Tentative gentamicin zone breakpoints were defined for two DD methods and QC ranges for 10 international reference strains were established. Our findings suggest that in resource-poor settings where MIC testing is not a feasible option, the DD methods can be used to indicate gentamicin resistance.

  • 19.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Persson, Katarina
    Örebro University, School of Medicine, Örebro University, Sweden.
    Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).2014In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 66, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.

  • 20.
    Bazzo, M. L.
    et al.
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Golfetto, L.
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Gaspar, P. C.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil.
    Pires, A. F.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil; University of Brasilia Postgraduate Program in Collective Health, Brasilia, Brazil.
    Ramos, M. C.
    Brazilian STD Society, Porto Alegre, Brazil.
    Franchini, M.
    Laboratory Consultant, Brasília, Brazil.
    Ferreira, W. A.
    Alfredo da Mata Foundation, Manaus, Brazil.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Benzaken, A. S.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil.
    First nationwide antimicrobial susceptibility surveillance for Neisseria gonorrhoeae in Brazil, 2015-162018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 7, p. 1854-1861Article in journal (Refereed)
    Abstract [en]

    Objectives: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns globally. Enhanced AMR surveillance for gonococci is essential worldwide; however, recent quality-assured gonococcal AMR surveillance in Latin America, including Brazil, has been limited. Our aims were to (i) establish the first nationwide gonococcal AMR surveillance, quality assured according to WHO standards, in Brazil, and (ii) describe the antimicrobial susceptibility of clinical gonococcal isolates collected from 2015 to 2016 in all five main regions (seven sentinel sites) of Brazil.

    Methods: Gonococcal isolates from 550 men with urethral discharge were examined for susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin, benzylpenicillin and tetracycline using the agar dilution method, according to CLSI recommendations and quality assured according to WHO standards.

    Results: The levels of resistance (intermediate susceptibility) to tetracycline, ciprofloxacin, benzylpenicillin and azithromycin were 61.6%(34.2%), 55.6%(0.5%), 37.1% (60.4%) and 6.9% (8.9%), respectively. All isolates were susceptible to ceftriaxone and cefixime using the US CLSI breakpoints. However, according to the European EUCAST cefixime breakpoints, 0.2% (n= 1) of isolates were cefixime resistant and 6.9% (n = 38) of isolates had a cefixime MIC bordering on resistance.

    Conclusions: This study describes the first national surveillance of gonococcal AMR in Brazil, which was quality assured according to WHO standards. The high resistance to ciprofloxacin (which promptly informed a revision of the Brazilian sexually transmitted infection treatment guideline), emerging resistance to azithromycin and decreasing susceptibility to extended-spectrum cephalosporins necessitate continuous surveillance of gonococcal AMR and ideally treatment failures, and increased awareness when prescribing treatment in Brazil.

  • 21.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Khalaf, Atika
    The PRO-CARE Group, School of Health and Society, Kristianstad University, Kristianstad, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Secreted gingipains from Porphyromonas gingivalis colonies exert potent immunomodulatory effects on human gingival fibroblasts2015In: Microbiological Research, ISSN 0944-5013, E-ISSN 1618-0623, Vol. 178, p. 18-26Article in journal (Refereed)
    Abstract [en]

    Periodontal pathogens, including Polphyromonas gingivalis, can form biofilms in dental pockets and cause inflammation, which is one of the underlying mechanisms involved in the development of periodontal disease, ultimately leading to tooth loss. Although P. gingivalis is protected in the biofilm, it can still cause damage and modulate inflammatory responses from the host, through secretion of microvesicles containing proteinases. The aim of this study was to evaluate the role of cysteine proteinases in P. gingivalis colony growth and development, and subsequent immunomodulatory effects on human gingival fibroblast. By comparing the wild type W50 with its gingipain deficient strains we show that cysteine proteinases are required by P. gingivalis to form morphologically normal colonies. The lysine-specific proteinase (Kgp), but not arginine-specific proteinases (Rgps), was associated with immunomodulation. P. gingivalis with Kgp affected the viability of gingival fibroblasts and modulated host inflammatory responses, including induction of TGF-beta 1 and suppression of CXCL8 and IL-6 accumulation. These results suggest that secreted products from P. gingivalis, including proteinases, are able to cause damage and significantly modulate the levels of inflammatory mediators, independent of a physical host-bacterial interaction. This study provides new insight of the pathogenesis of P. gingivalis and suggests gingipains as targets for diagnosis and treatment of periodontitis.

  • 22.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Lönn, Johanna
    Department of Oral Biology, Institute of Odontology, Malmö University, Malmö, Sweden; PEAS Research Institute, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Palm, Eleonor
    Örebro University, School of Medical Sciences.
    The lantibiotic gallidermin acts bactericidal against Staphylococcus epidermidis and Staphylococcus aureus and antagonizes the bacteria-induced proinflammatory responses in dermal fibroblasts2018In: MicrobiologyOpen, E-ISSN 2045-8827, Vol. 7, no 6, article id e606Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance needs to be tackled from new angles, and antimicrobial peptides could be future candidates for combating bacterial infections. This study aims to investigate in vitro the bactericidal effects of the lantibiotic gallidermin on Staphylococcus epidermidis and Staphylococcus aureus, possible cytotoxic effects and its impact on host-microbe interactions. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of gallidermin were determined, and cytotoxicity and proinflammatory effects of gallidermin on fibroblasts, red blood cells (RBCs) and in whole blood were investigated. Both MIC and MBC for all four tested strains of S. epidermidis was 6.25 μg/ml. Both MIC and MBC for methicillin-sensitive S. aureus was 12.5 μg/ml and for methicillin-resistant S. aureus (MRSA) 1.56 μg/ml. Gallidermin displayed no cytotoxic effects on fibroblasts, only a high dose of gallidermin induced low levels of CXCL8 and interleukin-6. Gallidermin hemolyzed less than 1% of human RBCs, and did not induce reactive oxygen species production or cell aggregation in whole blood. In cell culture, gallidermin inhibited the cytotoxic effects of the bacteria and totally suppressed the bacteria-induced release of CXCL8 and interleukin-6 from fibroblasts. We demonstrate that gallidermin, expressing low cell cytotoxicity, is a promising candidate for treating bacterial infections caused by S. epidermidis and S. aureus, especially MRSA.

  • 23.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Selegård, Robert
    Örebro University, School of Medical Sciences. Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Wiman, Emanuel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 5, article id ftx064Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease that is characterised by accumulation of pathogenic bacteria, including Porphyromonas gingivalis, in periodontal pockets. The lack of effective treatments has emphasised in an intense search for alternative methods to prevent bacterial colonisation and disease progression. Bacteriocins are bacterially produced antimicrobial peptides gaining increased consideration as alternatives to traditional antibiotics. We show rapid permeabilisation and aggregation of P. gingivalis by the two-peptide bacteriocin PLNC8 alpha beta. In a cell culture model, P. gingivalis was cytotoxic against gingival fibroblasts. The proteome profile of fibroblasts is severely affected by P. gingivalis, including induction of the ubiquitin-proteasome pathway. PLNC8 alpha beta enhanced the expression of growth factors and promoted cell proliferation, and suppressed proteins associated with apoptosis. PLNC8 alpha beta efficiently counteracted P. gingivalis-mediated cytotoxicity, increased expression of a large number of proteins and restored the levels of inflammatory mediators. In conclusion, we show that bacteriocin PLNC8 alpha beta displays dual effects by acting as a potent antimicrobial agent killing P. gingivalis and as a stimulatory factor promoting cell proliferation. We suggest preventive and therapeutical applications of PLNC8 alpha beta in periodontitis to supplement the host immune defence against P. gingivalis infection and support wound healing processes.

  • 24.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ito, Teruyo
    Ikeda, Megumi
    Ma, Xiao Xue
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Hiramatsu, Keiichi
    Novel type of staphylococcal cassette chromosome mec in a methicillin-resistant Staphylococcus aureus strain isolated in Sweden2008In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 10, p. 3512-3516Article in journal (Refereed)
    Abstract [en]

    We identified a novel type of staphylococcal cassette chromosome mec (SCCmec) element carried by methicillin-resistant Staphylococcus aureus (MRSA) strain JCSC6082 isolated in Sweden. The SCCmec element was demarcated by characteristic nucleotide sequences at both ends and was integrated at the 3' end of orfX. The element carried a novel combination of a type 5 ccr gene complex and class C1 mec gene complex. The J regions of the element were homologous to those of the SCCmercury element of S. aureus strain 85/2082, with nucleotide identity greater than 99%. However, the novel SCCmec element from JCSC6082 did not carry the mer operon nor Tn554, suggesting that evolution to SCCmec could have been from a common ancestor by acquisition of the class C1 mec gene complex. The novel SCCmec element from JCSC6082 was flanked by a novel SCC-like chromosome cassette (CC6082), which was demarcated by two direct repeats and could be excised from the chromosome independently of the SCCmec element. Our data suggest that novel SCCmec elements can be generated on the staphylococcal chromosome through the recombination between extant SCC elements and mec gene complexes.

  • 25.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ito, Teruyo
    Ma, Xiao Xue
    Ikeda, Megumi
    Watanabe, Shinya
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Hiramatsu, Keiichi
    Genetic diversity of methicillin-resistant Staphylococcus aureus carrying type IV SCCmec in Orebro County and the western region of Sweden2009In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 63, no 1, p. 32-41Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent studies have shown a predominance of type IV SCCmec among the methicillin-resistant Staphylococcus aureus (MRSA) isolated in the low endemic areas of Orebro County and the western region of Sweden. However, many of these isolates were not possible to classify as existing subtypes IVa, IVb, IVc or IVd. METHODS: We analysed 16 such MRSA isolates by multilocus sequence typing, spa typing, staphylocoagulase (SC) typing and detection of type IVg and IVh SCCmec. MRSA that remained as unknown type IV SCCmec were investigated by long-range PCR covering the J1 region; however, only two isolates were possible to amplify by PCR. The nucleotide sequences of the entire SCCmec of these two MRSA were determined. In addition, isolates that had unknown SC types were investigated by nucleotide sequencing of the coa genes. RESULTS: Five of 16 isolates were classified as type IVg SCCmec, and four isolates had type IVh SCCmec. Two subtypes of type IV SCCmec shared J1 regions previously identified in other types of SCCmec, types I.2 and II.2. The novel elements were designated as type IVi and IVj SCCmec. In addition, the genetic backgrounds of these Swedish MRSA were diverse and constituted at least nine sequence types and eight SC types, including four new types of SC. CONCLUSIONS: Type IV SCCmec is occurring in heterogeneous clones of MRSA in Sweden, and the majority of the type IV SCCmec were identified in community-acquired MRSA. We describe two novel subtypes of type IV SCCmec with common J1 regions shared by other types of SCCmec, which indicate that J1 regions occurred as primordial SCC.

  • 26.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Prévost, Gilles
    Laventie, Benoît-Joseph
    Keller, Daniel
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus2008In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 8, p. 878-884Article in journal (Other academic)
    Abstract [en]

    Methicillin-resistant Staphylococcus aureus isolated in the community (CA-MRSA) have been reported to carry the loci for Panton Valentine leukocidin (PVL) in high frequency. CA-MRSA in Orebro County, Sweden, constitutes at least 50% of MRSA and the PVL locus is detected in as many as 66% of these CA-MRSA isolates. The aim of this study was to characterize PVL-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus by molecular methods, to determine the nucleotide sequence of lukS-PV and lukF-PV in S. aureus isolates of different origins, and to investigate the biological consequence of variations occurring in the genes. The PVL-positive MRSA investigated were composed of six different STs (ST8, 36, 80, 152, 154, and 256). Six additional STs (ST5, 22, 25, 30, 88, and 567) were detected when investigating PVL-positive methicillin-susceptible S. aureus with MLST. Despite the different genetic origins of the isolates analyzed, the PVL genes were well conserved and only one mutation was non-synonymous. Evaluation of the consequence of this mutation showed that the mutated toxin and wild-type toxin had comparable biological activity on human polymorphonuclear cells.

  • 27.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    The origin of a methicillin-resistant Staphylococcus aureus isolate at a neonatal ward in Sweden: possible horizontal transfer of a staphylococcal cassette chromosome mec between methicillin-resistant Staphylococcus haemolyticus and Staphylococcus aureus2008In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 14, no 11, p. 1048-1056Article in journal (Refereed)
    Abstract [en]

    The first methicillin-resistant Staphylococcus aureus (MRSA) strain originated when a staphylococcal cassette chromosome mec (SCCmec) with the gene mecA was integrated into the chromosome of a susceptible S. aureus cell. The SCCmec elements are common among the coagulase-negative staphylococci, e.g. Staphylococcus haemolyticus, and these are considered to be potential SCCmec donors when new clones of MRSA arise. An outbreak of MRSA occurred at a neonatal intensive-care unit, and the isolates were all of sequence type (ST) 45, as characterized by multilocus sequence typing, but were not typeable with respect to SCCmec types I, II, III or IV. During the same time period, methicillin-resistant S. haemolyticus (MRSH) isolates identified in blood cultures at the same ward were found to be genotypically homogenous by pulsed-field gel electrophoresis, and did not carry a type I, II, III or IV SCCmec either. Thus, the hypothesis was raised that an SCCmec of MRSH had been transferred to a methicillin-susceptible S. aureus strain and thereby created a new clone of MRSA that caused the outbreak. This study showed that MRSA from the outbreak carried a ccrC and a class C mec complex that was also found among MRSH isolates. Partial sequencing of the mec complexes showed more than 99% homology, indicative of a common type V SCCmec. This finding may provide evidence for a recent horizontal transfer of an SCCmec from MRSH to an identified potential recipient, an ST45 methicillin-susceptible S. aureus strain, thereby creating a new clone of MRSA that caused the outbreak.

  • 28.
    Bergqvist, Åsa
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Smittspridning av campylobacter inom fjäderfäslakteri1986In: XV Nordiska veterinärkongressen – 15th Nordic Veterinary Congress, Stockholm 28/7–1/8 1986: Proceedings / [ed] Hans Kindahl, Ingemar Jämte, Stockholm: Sveriges Veterinärförbund , 1986, p. 355-358Conference paper (Refereed)
  • 29.
    Bernardino Ramos do Prado, Samira
    et al.
    Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
    Minguzzi, Beatriz Toledo
    Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
    Hoffmann, Christian
    Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, SP, Brazil .
    Fabi, João Paulo
    Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, SP, Brazil.
    Modulation of human gut microbiota by dietary fibers from unripe and ripe papayas: Distinct polysaccharide degradation using a colonic in vitro fermentation model2021In: Food Chemistry, ISSN 0308-8146, E-ISSN 1873-7072, Vol. 348, article id 129071Article in journal (Refereed)
    Abstract [en]

    Dietary fibers (DFs) consumption promotes a healthier gut through colonic fermentation and the modulation of different types of gut bacteria. The aim of this study is to evaluate the production of short-chain fatty acids (SCFA), metabolization of polysaccharides, and changes in the bacterial profile related to DFs extracted from the pulp of unripe and ripe papayas, using a batch colonic in vitro fermentation model. Our results show that fermentation of DFs from papayas induce the production of SCFAs and are utilized in different ways by intestinal microbiota. DFs from ripe papayas showed faster degradation by human gut microorganisms due to higher level of water-soluble polysaccharides. The fermentation of unripe papaya fibers increased the abundance of microorganisms belonging to family Clostridiaceae and genera Coprobacillus, Bulleidia, and Slackia, whereas both fibers increased Clostridium and Bacteroides, showing fruit ripeness affects the fermentation pattern of fruit fibers and their probable beneficial health aspects. 

  • 30.
    Berndtson, Eva
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Blomgren, Gunny
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Incidence of campylobacter on a broiler farm1987In: The IVth International Workshop on Campylobacter Infections, Department of Clinical Bacteriology, University Göteborg, June 16–18, 1987, Göteborg, Sweden: Programme and Abstracts, 1987, p. Abstract no. 17-Conference paper (Refereed)
  • 31.
    Berndtson, Eva
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Engvall, Anders
    Department of Epizootiology, National Veterinary Institute, Uppsala, Sweden.
    Colonization of mice and houseflies with Campylobacter jejuni1991In: Campylobacter  V: proceedings of the fifth International Workshop on Campylobacter Infections, Puerta Vallarta, Mexico, 25 February - 1 March, 1989 / [ed] Ruiz-Palacios, G. M., Calva, E., Ruiz-Palacios, B. R., Dept. of Infectious Diseases, Instituto Nacional de la Nutricion , 1991, p. 58-60Conference paper (Refereed)
  • 32.
    Bertrand, Yann J K
    et al.
    Science and Historical Investigations of Evolution Laboratory of Dubá, Dubá, Czech Republic.
    Johansson, Magnus
    Örebro University, School of Medical Sciences. School of Natural Science, Technology and Environmental Studies, Södertörn University, Huddinge, Sweden; RiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Norberg, Peter
    Department of Clinical Microbiology, Sahlgrenska University, Gothenburg, Sweden.
    Revisiting Recombination Signal in the Tick-Borne Encephalitis Virus: A Simulation Approach2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164435Article in journal (Refereed)
    Abstract [en]

    The hypothesis of wide spread reticulate evolution in Tick-Borne Encephalitis virus (TBEV) has recently gained momentum with several publications describing past recombination events involving various TBEV clades. Despite a large body of work, no consensus has yet emerged on TBEV evolutionary dynamics. Understanding the occurrence and frequency of recombination in TBEV bears significant impact on epidemiology, evolution, and vaccination with live vaccines. In this study, we investigated the possibility of detecting recombination events in TBEV by simulating recombinations at several locations on the virus' phylogenetic tree and for different lengths of recombining fragments. We derived estimations of rates of true and false positive for the detection of past recombination events for seven recombination detection algorithms. Our analytical framework can be applied to any investigation dealing with the difficult task of distinguishing genuine recombination signal from background noise. Our results suggest that the problem of false positives associated with low detection P-values in TBEV, is more insidious than generally acknowledged. We reappraised the recombination signals present in the empirical data, and showed that reliable signals could only be obtained in a few cases when highly genetically divergent strains were involved, whereas false positives were common among genetically similar strains. We thus conclude that recombination among wild-type TBEV strains may occur, which has potential implications for vaccination with live vaccines, but that these events are surprisingly rare.

  • 33.
    Bertrand, Yann
    et al.
    Dept Plant & Environm Sci, Univ Gothenburg, Gothenburg, Sweden.
    Töpel, Mats
    Dept Plant & Environm Sci, Univ Gothenburg, Gothenburg, Sweden.
    Elväng, Annelie
    Sch Life Sci, Södertörn Univ, Huddinge, Sweden.
    Melik, Wessam
    Sch Life Sci, Södertörn Univ, Huddinge, Sweden; Dept Genet Microbiol & Toxicol, Stockholm Univ, Stockholm, Sweden.
    Johansson, Magnus
    Sch Life Sci, Södertörn Univ, Huddinge, Sweden.
    First dating of a recombination event in mammalian tick-borne flaviviruses2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 2, article id e31981Article in journal (Refereed)
    Abstract [en]

    The mammalian tick-borne flavivirus group (MTBFG) contains viruses associated with important human and animal diseases such as encephalitis and hemorrhagic fever. In contrast to mosquito-borne flaviviruses where recombination events are frequent, the evolutionary dynamic within the MTBFG was believed to be essentially clonal. This assumption was challenged with the recent report of several homologous recombinations within the Tick-borne encephalitis virus (TBEV). We performed a thorough analysis of publicly available genomes in this group and found no compelling evidence for the previously identified recombinations. However, our results show for the first time that demonstrable recombination (i.e., with large statistical support and strong phylogenetic evidences) has occurred in the MTBFG, more specifically within the Louping ill virus lineage. Putative parents, recombinant strains and breakpoints were further tested for statistical significance using phylogenetic methods. We investigated the time of divergence between the recombinant and parental strains in a Bayesian framework. The recombination was estimated to have occurred during a window of 282 to 76 years before the present. By unravelling the temporal setting of the event, we adduce hypotheses about the ecological conditions that could account for the observed recombination.

  • 34.
    Björkqvist, Maria
    et al.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Liljedahl, M.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Zimmermann, J.
    Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Schollin, Jens
    Örebro University. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia2010In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 29, no 9, p. 1085-1093Article in journal (Refereed)
    Abstract [en]

    Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified (n = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2-3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.

  • 35.
    Bjørkeng, Eva
    et al.
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Sundsfjord, Arnfinn
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Sjöberg, Lennart
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hegstad, Kristin
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases and Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Clustering of polyclonal VanB-type vancomycin-resistant Enterococcus faecium in a low-endemic area was associated with CC17-genogroup strains harbouring transferable vanB2-Tn5382 and pRUM-like repA containing plasmids with axe-txe plasmid addiction systems2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, p. 247-258Article in journal (Refereed)
    Abstract [en]

    VanB-type vancomycin-resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad-spectrum antimicrobial therapy. Pulsed-field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi-locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital-adapted clonal complex 17 (CC17), harboured CC17-associated virulence genes, were vanB2-positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to > 256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2-Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM-like repA and a plasmid addiction system (axe-txe) shown by co-hybridization analysis of PFGE-separated S1-nuclease digested total DNA. The resistance plasmids were mainly of 120-kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2-resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB-type vancomycin-resistant Enterococcus faecium can persist in a low-endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.

  • 36.
    Boiko, Iryna
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Laboratory Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Bezkorovaina, Halyna
    Outpatient Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Frankenberg, Arkadii
    Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Onuchyna, Margarita
    Clinical Laboratory Department, Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-20182019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 7, p. 503-509Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally. However, recent gonococcal AMR data from Eastern Europe are extremely limited and no AMR data for strains spreading in Ukraine have ever been internationally published. We investigated the AMR of N. gonorrhoeae isolates in two regions of Ukraine (Ternopil 2013-2018, Dnipropetrovsk 2013-2014), and, where information was available, the treatment administered to the corresponding gonorrhoea patients. Determination of minimum inhibitory concentration (MIC) of eight antimicrobials was performed using Etest and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Overall, 9.3% of the examined 150 isolates were resistant to ciprofloxacin, 6.0% to tetracycline, 2.0% to azithromycin, and 0.7% to benzylpenicillin. No isolates were resistant to ceftriaxone, cefixime, spectinomycin, or gentamicin. However, one (0.7%) isolate showed a MIC value of 0.125 mg/L for both ceftriaxone and cefixime, i.e., bordering resistance. Eighty-eight (67.2%) of 131 patients were administered dual therapy (ceftriaxone 1 g plus doxycycline/clarithromycin/azithromycin/ofloxacin) and 22 (16.8%) ceftriaxone 1 g monotherapy. Worryingly, 21 (16.0%) patients received monotherapy with clarithromycin/doxycycline/azithromycin/ofloxacin/benzylpenicillin. In conclusion, the antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipropetrovsk, Ukraine during 2013-2018 was high. Low levels of resistance to ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were found, but no resistance to the internationally recommended ceftriaxone, cefixime, or spectinomycin. Ceftriaxone 1 g should remain as empiric first-line treatment, in dual therapy with azithromycin or doxycycline or in monotherapy. Continued and expanded gonococcal AMR surveillance in Ukraine is essential to monitor the susceptibility to particularly extended-spectrum cephalosporins, azithromycin and doxycycline.

  • 37.
    Brehony, Carina
    et al.
    Dept Zool, Univ Oxford, Oxford, England..
    Trotter, Caroline L.
    Dept Vet Med, Univ Cambridge, Cambridge, England.
    Ramsay, Mary E.
    Publ Hlth England, London, England.
    Chandra, Manosree
    Publ Hlth England, London, England.
    Jolley, Keith A.
    Dept Zool, Univ Oxford, Oxford, England.
    van der Ende, Arie
    Dept Med Microbiol, Netherlands Reference Lab Bacterial Meningitis, Acad Med Ctr, Univ Amsterdam, Amsterdam, Netherlands.
    Carion, Francoise
    Meningococcal Reference Lab, Sci Inst Publ Hlth, Brussels, Belgium.
    Berthelsen, Lene
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hoffmann, Steen
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hardardottir, Hjordis
    Dept Microbiol, Landspitali Univ Hosp, Reykjavik, Iceland.
    Vazquez, Julio A.
    Meningococcal Reference Lab, Madrid, Spain.
    Murphy, Karen
    Irish Meningococcal & Meningitis Reference Lab, Dublin, Ireland.
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Canica, Manuela
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Ferreira, Eugenia
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Diggle, Mathew
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Edwards, Giles F.
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Taha, Muhamed-Kheir
    Inst Pasteur, Natl Reference Ctr Meningococci, Institut Pasteur, Paris, France.
    Stefanelli, Paola
    Dept Infect Parasit & Immune Mediated Dis, Ist Super Sanita, Rome, Italy.
    Kriz, Paula
    Natl Reference Lab Meningococcal Infect, Natl Inst Publ Hlth, Prague, Czech Republic.
    Gray, Steve J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Fox, Andrew J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Claus, Heike
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Vogel, Ulrich
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Tzanakaki, Georgina
    Natl Meningococcal Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Heuberger, Sigrid
    Natl Reference Ctr Meningococci, Inst Med Microbiol & Hyg, Graz, Austria.
    Caugant, Dominique A.
    Dept Bacteriol & Immunol, Norwegian Inst Publ Hlth, Oslo, Norway.
    Frosch, Matthias
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Maiden, Martin C. J.
    Dept Zool, Univ Oxford, Oxford, England.
    Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 6, p. 847-853Article in journal (Refereed)
    Abstract [en]

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.

  • 38.
    Brial, François
    et al.
    UMRS 1124 INSERM, Université de Paris Descartes, Paris, France.
    Chilloux, Julien
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
    Nielsen, Trine
    Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark.
    Vieira-Silva, Sara
    Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
    Falony, Gwen
    Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
    Andrikopoulos, Petros
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK.
    Olanipekun, Michael
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK.
    Hoyles, Lesley
    Department of Biosciences, Nottingham Trent University, Nottingham, UK.
    Djouadi, Fatima
    Centre de Recherche des Cordeliers, Université Paris Descartes, Paris, France; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Paris, France.
    Neves, Ana L.
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
    Rodriguez-Martinez, Andrea
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
    Mouawad, Ghiwa Ishac
    UMRS 1124 INSERM, Université de Paris Descartes, Paris, France.
    Pons, Nicolas
    Metagenopolis, INRAE, Paris, Île-de-France, France.
    Forslund, Sofia
    Forslund Lab, Max Delbrück Centrum für Molekulare Medizin Experimental and Clinical Research Center, Berlin, Berlin, Germany.
    Le-Chatelier, Emmanuelle
    Metagenopolis, INRAE, Paris, Île-de-France, France.
    Le Lay, Aurélie
    UMRS 1124 INSERM, Université de Paris Descartes, Paris, France.
    Nicholson, Jeremy
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
    Hansen, Torben
    Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Clément, Karine
    INSERM, U1166, team 6 Nutriomique, Université Pierre et Marie Curie-Paris 6, Paris, France; Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
    Oresic, Matej
    Örebro University, School of Medical Sciences.
    Bork, Peer
    Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
    Ehrlich, Stanislav Dusko
    Metagenopolis, INRAE, Paris, Île-de-France, France; Center for Host Microbiome Interactions, King's College London Dental Institute, London, UK.
    Raes, Jeroen
    Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.
    Pedersen, Oluf Borbye
    Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.
    Gauguier, Dominique
    UMRS 1124 INSERM, Université de Paris Descartes, Paris, France.
    Dumas, Marc-Emmanuel
    Section of Biomolecular Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK; McGill Genome Centre & Department of Human Genetics, McGill University, Montréal, Québec, Canada; European Genomics Institute for Diabetes, INSERM U1283, CNRS UMR8199, Institut Pasteur de Lille, Lille University Hospital, Unversity of Lille, Lille, France.
    Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 11, p. 2105-2114Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health.

    DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes.

    RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion.

    CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.

  • 39.
    Broeker, Michael
    et al.
    Novartis Vaccines & Diagnost GmbH, Marburg, Germany.
    Bukovski, Suzana
    Univ Hosp Infect Dis Dr Fran Mihaljevic, Zagreb, Croatia.
    Culic, Davor
    Haemophilus & Meningococcus Reference Lab, Ctr Microbiol, Inst Publ Hlth, Srbija, Serbia.
    Jacobsson, Susanne
    Örebro University Hospital.
    Koliou, Maria
    Unit Surveillance & Control Communicable Dis, Minist Hlth, Nikosia, Cyprus.
    Kuusi, Markku
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Simoes, Maria Joao
    Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal.
    Skoczynska, Anna
    Natl Reference Ctr Bacterial Meningitis, Natl Med Inst, Warsaw, Poland.
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Taha, Muhamed-Keir
    Invas Bacterial Infect Unit, Inst Pasteur, Paris, France.
    Tzanakaki, Georgina
    Natl Meningitis Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Meningococcal serogroup Y emergence in Europe High importance in some European regions in 20122014In: Human Vaccines & Immunotherapeutics, ISSN 2164-5515, E-ISSN 2164-554X, Vol. 10, no 6, p. 1725-1728Article in journal (Refereed)
    Abstract [en]

    Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. 1,2 Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.

  • 40.
    Broman, T.
    et al.
    Department of Molecular Biology, Umeå University, Umeå, Sweden.
    Palmgren, H.
    Department of Molecular Biology, Umeå University, Umeå, Sweden; Department of Infectious Diseases, Umeå University, Umeå, Sweden.
    Bergström, S.
    Department of Molecular Biology, Umeå University, Umeå, Sweden.
    Sellin, M.
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden .
    Waldenström, J.
    Department of Animal Ecology, Lund University, Lund, Sweden.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Swed. Univ. of Agricultural Sciences, Uppsala, Sweden .
    Olsen, B.
    Department of Infectious Diseases, Umeå University, Umeå, Sweden; Res. Inst. Zoonotic Ecol./Epidemiol., Färjestaden, Sweden .
    Campylobacter jejuni in black-headed gulls (Larus ridibundus): prevalence, genotypes, and influence on C. jejuni epidemiology2002In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 40, no 12, p. 4594-4602Article in journal (Refereed)
    Abstract [en]

    Campylobacteriosis is a zoonotic disease in which birds have been suggested to play an important role as a reservoir. We investigated the prevalence of Campylobacter jejuni subsp. jejuni in black-headed gulls (Larus ridibundus) in southern Sweden with the aim of examining the nature of C. jejuni infection in this bird species. Birds were sampled in four sampling series each year during 1999 (n = 419) and 2000 (n = 365). Longitudinally sampled C. jejuni isolates from individual gulls were subjected to macrorestriction profiling (MRP) by pulsed-field gel electrophoresis to investigate the genotypical stability during the natural course of infection. Furthermore, a subset (n = 76) of black-headed gull isolates was compared to isolates from broiler chickens (n = 38) and humans (n = 56) originating from the same geographic area. We found a pronounced seasonal variation in C. jejuni carriage, with the highest rates found in late autumn. MRP similarities were higher between isolates of human and broiler chicken origin, than between those of wild bird origin and either of the other two hosts. However, identical MRPs were found in two gull isolates and one human isolate after digestion with two restriction enzymes, strongly indicating that they may have been colonized by the same clone of C. jejuni. The MRPs most prevalent in gull isolates did not occur among isolates from humans and broiler chickens, suggesting the existence of a subpopulation of C. jejuni adapted to species-specific colonization or environmental survival.

  • 41.
    Brüggemann, Holger
    et al.
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Jensen, Anders
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Nazipi, Seven
    Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Bioscience, Aarhus University, Aarhus, Denmark.
    Aslan, Husnu
    Department of Bioscience, Aarhus University, Aarhus, Denmark.
    Meyer, Rikke Louise
    Department of Bioscience, Aarhus University, Aarhus, Denmark.
    Poehlein, Anja
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, Georg-August University Göttingen, Göttingen, Germany.
    Brzuszkiewicz, Elzbieta
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, Georg-August University Göttingen, Göttingen, Germany.
    Al-Zeer, Munir A.
    Department of Applied Biochemistry, Institute of Biotechnology, TU Berlin, Berlin, Germany.
    Brinkmann, Volker
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 266Article in journal (Refereed)
    Abstract [en]

    Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.

  • 42.
    Brüggemann, Holger
    et al.
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Poehlein, Anja
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
    Brzuszkiewicz, Elzbieta
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
    Scavenius, Carsten
    Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
    Enghild, Jan J.
    Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
    Al-Zeer, Munir A.
    Department of Applied Biochemistry, Institute of Biotechnology, Technical University of Berlin, Berlin, Germany.
    Brinkmann, Volker
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany.
    Jensen, Anders
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Staphylococcus saccharolyticus Isolated From Blood Cultures and Prosthetic Joint Infections Exhibits Excessive Genome Decay2019In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 10, article id 478Article in journal (Refereed)
    Abstract [en]

    The slow-growing, anaerobic, coagulase-negative species Staphylococcus saccharolyticus is found on human skin and in clinical specimens but its pathogenic potential is unclear. Here, we investigated clinical isolates and sequenced the genomes of seven strains of S. saccharolyticus. Phylogenomic analyses showed that the closest relative of S. saccharolyticus is Staphylococcus capitis with an average nucleotide identity of 80%. Previously sequenced strains assigned to S. saccharoiyticus are misclassified and belong to S. capitis. Based on single nucleotide polymorphisms of the core genome, the population of S. saccharolyticus can be divided into two clades that also differ in a few larger genomic islands as part of the flexible genome. An unexpected feature of S. saccharolyticus is extensive genome decay, with over 300 pseudogenes, indicating ongoing reductive evolution. Many genes of the core metabolism are not functional, rendering the species auxotrophic for several amino acids, which could explain its slow growth and need for fastidious growth conditions. Secreted proteins of S. saccharolyticus were determined; they include stress response proteins such as heat and oxidative stress-related factors, as well as immunodominant staphylococcal surface antigens and enzymes that can degrade host tissue components. The strains secrete lipases and a hyaluronic acid lyase. Hyaluronidase as well as urease activities were detected in biochemical assays, with Glade-specific differences. Our study revealed that S. saccharolyticus has adapted its genome, possibly due to a recent change of habitat; moreover, the data imply that the species has tissue-invasive potential and might cause prosthetic joint infections.

  • 43.
    Börjesson, Stefan
    et al.
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Greko, Christina
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    Myrenås, Mattias
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    Landén, Annica
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    Nilsson, Oskar
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    Pedersen, Karl
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    A link between the newly described colistin resistance gene mcr-9 and clinical Enterobacteriaceae isolates carrying blaSHV-12 from horses in Sweden2020In: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 20, p. 285-289Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to investigate the occurrence of the newly described transferable colistin resistance gene mcr-9 in extended-spectrum β-lactamase (ESBL)-producing clinical Enterobacteriaceae isolates from horses in Sweden.

    METHODS: A total of 56 whole-genome sequenced ESBL-producing Enterobacteriaceae isolates from horses were subjected to in silico detection of antimicrobial resistance genes and identification of plasmid replicons types. The colistin minimum inhibitory concentration (MIC) for mcr-positive isolates was determined by broth microdilution. Relatedness between Enterobacteriaceae carrying mcr genes was determined by multilocus sequence typing (MLST) and core genome MLST.

    RESULTS: Thirty ESBL-producing Enterobacteriaceae isolates from horses were positive for the colistin resistance gene mcr-9. These isolates included Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Citrobacter freundii and belonged to diverse MLST sequence types within each species. Two of the mcr-9-containing isolates originated from the same horse. All mcr-9-positive isolates had colistin MICs below or equal to the EUCAST epidemiological cut-off value of 2 mg/L and were negative for the two potential regulatory genes qseB-like and qseC-like for mcr-9. Except for one isolate carrying only blaTEM-1B, all of the isolates carried blaSHV-12 and blaTEM-1B, and were all considered multidrug-resistant as they harboured genes encoding resistance to aminoglycosides, chloramphenicol, fosfomycin, macrolides, quinolones, sulfonamides, trimethoprim and tetracyclines. Plasmid replicon types IncHI2 and IncHI2A were detected in all mcr-9-positive isolates.

    CONCLUSION: The occurrence of mcr-9 was common among clinical ESBL-producing Enterobacteriaceae isolates from horses in Sweden and was linked to the ESBL-encoding gene blaSHV-12 and plasmid replicon types IncHI2 and IncHI2A.

  • 44.
    Börjesson, Stefan
    et al.
    Department of Biomedical and Clinical Sciences, Linköping University, 58183, Linköping, Sweden; Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 75189, Uppsala, Sweden.
    Gunnarsson, Lotta
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 75189, Uppsala, Sweden.
    Landén, Annica
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 75189, Uppsala, Sweden.
    Grönlund, Ulrika
    AniCura, Vendevägen 89, 182 32, Danderyd, Sweden.
    Low occurrence of extended-spectrum cephalosporinase producing Enterobacteriaceae and no detection of methicillin-resistant coagulase-positive staphylococci in healthy dogs in Sweden2020In: Acta Veterinaria Scandinavica, ISSN 0044-605X, E-ISSN 1751-0147, Vol. 62, article id 18Article in journal (Refereed)
    Abstract [en]

    Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3-2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.

  • 45.
    Börjesson, Stefan
    et al.
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), SE751 89, Uppsala, Sweden.
    Gómez-Sanz, E
    Department of Biochemistry and Molecular Biology, University of La Rioja, Logroño, Spain; Environmental Genomics and Systems Biology Research Group, Institute of Natural Resource Sciences, Zurich University of Applied Sciences (ZHAW), Wädenswil, Switzerland.
    Ekström, K
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), SE751 89, Uppsala, Sweden.
    Torres, C
    Department of Biochemistry and Molecular Biology, University of La Rioja, Logroño, Spain.
    Grönlund, U
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), SE751 89, Uppsala, Sweden; Swedish University of Agriculture Sciences, Uppsala, Sweden.
    Staphylococcus pseudintermedius can be misdiagnosed as Staphylococcus aureus in humans with dog bite wounds.2015In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 34, p. 839-844Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate whether S. pseudintermedius is misdiagnosed as S. aureus by clinical laboratories when isolated from humans with dog bite wounds. In addition, we attempted to determine whether S. pseudintermedius isolates related to dog bite wounds share phenotypic and genotypic traits. S. pseudintermedius was identified by PCR targeting the nuc gene. Isolates were tested for antibiotic susceptibility using VetMIC GP-mo microdilution panels. The occurrence of genes encoding leukocidins, exfoliatins, pyrogenic toxin superantigens and enterotoxins was determined by PCR. The relatedness of S. pseudintermedius isolates was investigated using Multi Locus Sequence Typing (MLST). Out of 101 isolates defined as S. aureus by human clinical microbiology laboratories, 13 isolates were re-identified as S. pseudintermedius and one isolate was confirmed to carry the mecA gene, i.e. methicillin-resistant (MRSP). The MRSP isolate was also defined as multi-resistant. Two methicillin-susceptible S. pseudintermedius isolates were also multi-resistant and five were susceptible to all antibiotics tested. With the exception of three S. pseudintermedius isolates belonging to multi locus sequence type (MLST) 158, all the isolates belonged to unique STs. All isolates contained lukS/F-I, siet and se-int, and expA were identified in two isolates and expB and sec canine-sel in one isolate respectively. S. pseudintermedius is frequently misdiagnosed as S. aureus from humans with dog bite wounds showing that it can act as an opportunistic pathogen in humans. No common phenotypic and genotypic traits shared by the S. pseudintermedius isolates could be identified.

  • 46.
    Börjesson, Stefan
    et al.
    National Veterinary Institute, Uppsala, Sweden.
    Ny, Sofia
    Public Health Agency of Sweden, Stockholm, Sweden.
    Egervärn, Maria
    National Food Agency, Uppsala, Sweden.
    Bergström, Jakob
    Public Health Agency of Sweden, Stockholm, Sweden.
    Rosengren, Åsa
    National Food Agency, Uppsala, Sweden.
    Englund, Stina
    National Veterinary Institute, Uppsala, Sweden.
    Löfmark, Sonja
    Public Health Agency of Sweden, Stockholm, Sweden.
    Byfors, Sara
    Public Health Agency of Sweden, Stockholm, Sweden.
    Limited Dissemination of Extended-Spectrum β-Lactamase- and Plasmid-Encoded AmpC-Producing Escherichia coli from Food and Farm Animals, Sweden2016In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 22, no 4, p. 634-640Article in journal (Refereed)
    Abstract [en]

    Extended-spectrum β-lactamase (ESBL)- and plasmid-encoded ampC (pAmpC)-producing Enterobacteriaceae might spread from farm animals to humans through food. However, most studies have been limited in number of isolates tested and areas studied. We examined genetic relatedness of 716 isolates from 4,854 samples collected from humans, farm animals, and foods in Sweden to determine whether foods and farm animals might act as reservoirs and dissemination routes for ESBL/pAmpC-producing Escherichia coli. Results showed that clonal spread to humans appears unlikely. However, we found limited dissemination of genes encoding ESBL/pAmpC and plasmids carrying these genes from foods and farm animals to healthy humans and patients. Poultry and chicken meat might be a reservoir and dissemination route to humans. Although we found no evidence of clonal spread of ESBL/pAmpC-producing E. coli from farm animals or foods to humans, ESBL/pAmpC-producing E. coli with identical genes and plasmids were present in farm animals, foods, and humans.

  • 47.
    Carlberg, Michael
    et al.
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Hardell, Lennart
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of Mobile Phone and Cordless Phone Use and Glioma Risk Using the Bradford Hill Viewpoints from 1965 on Association or Causation2017In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2017, article id 9218486Article, review/survey (Refereed)
    Abstract [en]

    Objective: Bradford Hill's viewpoints from 1965 on association or causation were used on glioma risk and use of mobile or cordless phones.

    Methods: All nine viewpoints were evaluated based on epidemiology and laboratory studies.

    Results: Strength: meta-analysis of case-control studies gave odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.31-2.76 with highest cumulative exposure. Consistency: the risk increased with latency, meta-analysis gave in the 10+ years' latency group OR = 1.62, 95% CI = 1.20-2.19. Specificity: increased risk for glioma was in the temporal lobe. Using meningioma cases as comparison group still increased the risk. Temporality: highest risk was in the 20+ years' latency group, OR = 2.01, 95% CI =1.41-2.88, for wireless phones. Biological gradient: cumulative use of wireless phones increased the risk. Plausibility: animal studies showed an increased incidence of glioma and malignant schwannoma in rats exposed to radiofrequency (RF) radiation. There is increased production of reactive oxygen species (ROS) from RF radiation. Coherence: there is a change in the natural history of glioma and increasing incidence. Experiment: antioxidants reduced ROS production from RF radiation. Analogy: there is an increased risk in subjects exposed to extremely low-frequency electromagnetic fields.

    Conclusion: RF radiation should be regarded as a human carcinogen causing glioma.

  • 48.
    Carstens, Adam
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Internal Medicine, Ersta hospital, Stockholm, Sweden.
    Roos, Annika
    Department of Microbiology, Tumor and Cell biology & Science for Life Laboratory, Karolinska Institute, Solna, Sweden.
    Andreasson, Anna
    Department of Microbiology, Tumor and Cell biology & Science for Life Laboratory, Karolinska Institute, Solna, Sweden; Division for Family Medicine, Karolinska Institute, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Agréus, Lars
    Division for Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell biology & Science for Life Laboratory, Karolinska Institute, Solna, Sweden.
    Differential clustering of faecal and mucosa-associated microbiota in healthy individuals2018In: Journal of Digestive Diseases, ISSN 1751-2972, E-ISSN 1751-2980, Vol. 19, no 12, p. 745-752Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Faecal samples are often used to characterise gut microbiota, since they are easily collected. However, whether or not the faecal microbiota differ from the mucosa-associated microbiota remains largely unknown. This may be specifically relevant in conditions that are characterised by complex mucosal microbe-host interactions, such as Crohn's disease. We aimed to determine the degree of agreement between faecal and mucosal microbiota profiles in healthy individuals, using two commonly used collection procedures.

    MATERIAL AND METHODS: The gut microbiota composition of faecal samples (sent at ambient temperature before storage at -70°C) and of colonic biopsies (obtained at endoscopy and immediately stored at -70°C) was determined by sequencing the 16S rRNA gene. Thirty-one randomly selected healthy individuals from the population-based colonoscopy (Popcol) study were included.

    RESULTS: Faecal samples were characterised by a reduced degree of richness (p<0.0001) and diversity (p=0.016), and also differences in several phyla, including a lower relative abundance of Proteobacteria (p<0.0001) and Verrucomicrobia (p=0.008) than in biopsies. Only 3 of 30 individuals had a similar faecal and mucosal microbiota profile, based on weighted UniFrac analysis. A difference in Crohn's disease dysbiosis-associated bacteria was observed, including a lower relative abundance of Faecalibacterium (p=0.004) and a higher relative abundance of Ruminococcus (p=0.001) in faeces than in biopsies.

    CONCLUSIONS: Analysis of faecal samples that have been transported at ambient temperature does not adequately reflect the colonic mucosa-associated microbiota in healthy individuals. These findings have implications for the interpretation of the previous literature, and may be specifically relevant to studies on Crohn's disease.

  • 49.
    Chen, Baoli
    et al.
    Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, Shandong Province, China.
    Berglund, Björn
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State .
    Wang, Shuang
    Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, Shandong Province, China.
    Börjesson, Stefan
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden; Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Bi, Zhenqiang
    Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, Shandong Province, China.
    Nilsson, Maud
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Yin, Hong
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Zheng, Beiwen
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated .
    Xiao, Yonghong
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated .
    Bi, Zhenwang
    Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, No. 16992 Jingshi Road, Jinan 250014, Shandong Province, China; Shandong Academy of Clinical Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.
    Nilsson, Lennart E
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Rapid increase in occurrence of carbapenem-resistant Enterobacteriaceae in healthy rural residents in Shandong Province, China, from 2015 to 20172022In: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 28, p. 38-42Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The global increase in carbapenem-resistant Enterobacteriaceae (CRE) is a growing health concern. Infections caused by CRE are associated with increased mortality and length of hospital stay, emphasising the health and economic burden posed by these pathogens. Although CRE can inhabit the human gut asymptomatically, colonisation with CRE is associated with an increased risk of CRE infection and mortality. In this study, we investigated the occurrence and characteristics of CRE in faecal samples from healthy persons in 12 villages in Shandong Province, China.

    METHODS: Screening for CRE in faecal samples was performed by selective cultivation. Minimum inhibitory concentrations (MICs) of meropenem were determined by the agar dilution method. Multilocus sequence typing (MLST) and carbapenemase gene carriage of the isolates were determined by whole-genome sequencing. Genetic relatedness of Escherichia coli isolates was determined by core genome MLST.

    RESULTS: CRE carriage increased from 2.4% in 2015 to 13.4% in 2017. Most CRE isolates (93.0%) were E. coli and all carried NDM-type carbapenemases. Sequence types (STs) among the E. coli isolates were diverse. The single most common ST was the highly epidemic strain ST167, which was only observed in 2017.

    CONCLUSION: We report a rapid increase in occurrence of CRE (from 2.4% to 13.4%) among faecal samples collected from healthy rural residents of Shandong Province from 2015 to 2017. Colonisation with CRE is known to increase the risk of CRE infection, and the worrying deterioration of the epidemiological situation in the region reported here indicates a need for further monitoring and possible interventions.

  • 50.
    Connolly, Kristie L.
    et al.
    Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States.
    Eakin, Ann E.
    Division of Microbiology and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
    Gomez, Carolina
    Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States.
    Osborn, Blaire L.
    Division of Microbiology and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Jerse, Ann E.
    Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States .
    Pharmacokinetic Data Are Predictive of In Vivo Efficacy for Cefixime and Ceftriaxone against Susceptible and Resistant Neisseria gonorrhoeae Strains in the Gonorrhea Mouse Model2019In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, no 3, article id e01644-18Article in journal (Refereed)
    Abstract [en]

    There is a pressing need for drug development for gonorrhea. Here we describe pharmacokinetics/pharmacodynamics (PK/PD) analysis of extended-spectrum cephalosporins (ESC) against drug-susceptible and drug-resistant gonococcal strains in a murine genital tract infection model. PK determined in uninfected mice displayed a clear dose response in plasma levels following single doses of ceftriaxone (CRO) (intraperitoneal) or cefixime (CFM) (oral). The observed doses required for efficacy against ESCS strain FA1090 were 5 mg/kg (CRO) and 12 mg/kg (CFM); these doses had estimated therapeutic times (time of free drug above the MIC, fTMIC) of 24 h and 37 h, respectively. No single dose of CRO or CFM was effective against the ESCR strain H041. However, fractionation (TIDq8h) of a 120 mg/kg dose of CRO resulted in estimated therapeutic times in the range of 23 h and cleared H041 infection in a majority (90%) of mice, comparable to gentamicin. In contrast, multiple CFM doses of 120 or 300 mg/kg administered TIDq8h cleared infection in ≤ 50% of mice with therapeutic times estimated from single-dose PK data, of 13 and 27 h, respectively. This study reveals a clear relationship between plasma ESC levels and bacterial clearance rates in the gonorrhea mouse model. The PK/PD relationships in mice reflected that observed in humans with in vivo efficacy against an ESCS strain requiring doses that yielded an fTMIC in excess of 20-24 h. PK data also accurately predicted the failure of single doses of ESCs against an ESCR strain and were useful in designing effective dosing regimens.

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