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Long term molecular epidemiology of methicillin-susceptible staphylococcus aureus bacteremia isolates in Sweden
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
Alere Technologies GmbH, Jena, Germany; Institute for Medical Microbiology and Hygiene, TU Dresden, Dresden, Germany.
Örebro University Hospital, Örebro, Sweden. (Clinical Epidemiology and Biostatistics)
Alere Technologies GmbH, Jena, Germany.
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, article id e114276Article in journal (Refereed) Published
Abstract [en]

Staphylococcus aureus is one of the major pathogens that causes bacteremia; therefore, it is important to understand the long-term molecular epidemiology of S. aureus bacteremia infections. In particular, little is known about the population structure of methicillin-sensitive S. aureus (MSSA) compared to that of methicillin-resistant S. aureus. We investigated potential changes in the MSSA molecular epidemiology in Örebro County, Sweden, from 1980 through 2010. 400 MSSA bacteremia isolates, the first 100 isolated each decade from 1980 through 2010, were retrospectively identified and analyzed regarding assignment to clonal complexes (CCs), presence of virulence genes and antibiotic resistant determinants with DNA microarray-based genotyping. 24 different CCs were identified. Most isolates (80%) belonged to 6 predominant lineages. Of those, the number of isolates assigned to CC5 and CC15 increased, and those assigned to CC8, CC25, and CC30 decreased. The most prevalent clone, CC45, did not show a significant change in prevalence during the study period. A change in prevalence was observed for some of the virulence genes, mainly attributed with their association to certain CCs. With the exception of the common blaZ gene (encoding penicillinase), antibiotic resistance genes were only sporadically detected. In conclusion, the MSSA population structure was genetically diverse. We observed decadal changes in assignments to five predominant clones, and corresponding changes in the prevalence of some virulence genes linked to CC affiliation. In light of the restrictive antibiotics prescriptions and extensive infection control procedures in Sweden, antibiotic resistance genes were rarely detected and their prevalence unaffected during the study period.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library Science , 2014. Vol. 9, no 12, article id e114276
National Category
Infectious Medicine Orthopaedics Clinical Laboratory Medicine
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-39966DOI: 10.1371/journal.pone.0114276ISI: 000346907200063PubMedID: 25479442Scopus ID: 2-s2.0-84917739022OAI: oai:DiVA.org:oru-39966DiVA, id: diva2:774290
Note

Funding Agency:

Research Committee of the County Council of Örebro University Hospital

Available from: 2014-12-22 Created: 2014-12-22 Last updated: 2018-09-18Bibliographically approved
In thesis
1. Staphylococcus aureus bacteremia, molecular epidemiology and host immune response
Open this publication in new window or tab >>Staphylococcus aureus bacteremia, molecular epidemiology and host immune response
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Staphylococcus aureus is a major pathogen responsible for a considerable disease burden worldwide. It may cause a wide array of infections, from superficial skin infections to invasive bacteremia and complications such as infective endocarditis (IE) and osteomyelitis. This thesis aimed to investigate aspects of the molecular epidemiology of S. aureus and host immune response in relation to disease manifestation, severity, and over time during S. aureus bacteremia (SAB).

Genotypic characteristics in isolates causing colonization, bacteremia, and bacteremia with IE were studied. The S. aureus population was genetically diverse and certain clones with their set of often lineage-specific virulence genes were associated with invasive disease. Characterization of the long-term molecular epidemiology of MSSA bacteremia showed an increased prevalence of CC5 and CC15, while CC8, CC25 and CC30 declined. Antibiotic resistance pattern was favorable and unaffected.

Further, different aspects of host immune response were explored in patients with SAB during the acute phase of bacteremia. When investigating the NLRP3 inflammasome signaling, induced caspase-1 activity was found, with a great inter-individual variation between patients, and subsequent release of IL-18, indicating inflammasome activity. Finally, the dynamics of MHC class II related genes HLA-DRA and CD74 were analyzed as markers of immunosuppression. Patients with complicated SAB had significantly lower HLA-DRA expression than patients with uncomplicated bacteremia, demonstrating an association between complicated SAB and impaired immune function.

In conclusion, the S. aureus genotype, as well as host factors reflected by inter-individual variations in inflammasome signaling and immune function, may all contribute to disease manifestation and outcome during SAB. An ability to measure the immune response early and continuously during the hospital stay and course of bacteremia could offer a way to tailor patient management and treatment in an individualized way.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. p. 75
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 158
Keywords
Staphylococcus aureus, molecular epidemiology, DNAmicroarray, bacteremia, sepsis, NLRP3, inflammasome, caspase-1, HLA-DR, HLA-DRA, CD74
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-54675 (URN)978-91-7529-181-9 (ISBN)
Public defence
2017-03-31, Campus USÖ, hörsal C3, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-01-13 Created: 2017-01-13 Last updated: 2018-01-13Bibliographically approved

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Rasmussen, GunlögSöderquist, Bo

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