oru.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus
Örebro University, School of Health and Medical Sciences.
Show others and affiliations
2008 (English)In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 8, p. 878-884Article in journal (Other academic) Published
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.

Place, publisher, year, edition, pages
Paris: Elsevier , 2008. Vol. 10, no 8, p. 878-884
Keywords [en]
Bacterial Proteins/genetics/toxicity, Bacterial Toxins/*genetics/toxicity, Cluster Analysis, Community-Acquired Infections/microbiology, Conserved Sequence, DNA; Bacterial/chemistry/genetics, Exotoxins/*genetics/toxicity, Genotype, Humans, Leukocidins/*genetics/toxicity, Methicillin Resistance, Neutrophils/drug effects, Sequence Analysis; DNA, Staphylococcal Infections/microbiology, Staphylococcus aureus/classification/*drug effects/*genetics/isolation & purification, Sweden
National Category
Medical and Health Sciences Microbiology in the medical area
Research subject
Immunology
Identifiers
URN: urn:nbn:se:oru:diva-3476DOI: 10.1016/j.micinf.2008.04.018PubMedID: 18656408OAI: oai:DiVA.org:oru-3476DiVA, id: diva2:137773
Available from: 2008-12-08 Created: 2008-12-08 Last updated: 2018-01-13Bibliographically approved
In thesis
1. Molecular epidemiology of methicillin-resistant staphylococcus aureus: epidemiological aspects of MRSA and the dissemination in the community and in hospitals
Open this publication in new window or tab >>Molecular epidemiology of methicillin-resistant staphylococcus aureus: epidemiological aspects of MRSA and the dissemination in the community and in hospitals
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Methicillin-resistenta Staphylococcus aureus (MRSA) som bär på genen mecA, har förekommit och spridit sig över hela världen, främst i sjukhusmiljö, och orsakat utbrott av vårdrelaterade (så kallade nosokomiala) infektioner. Dessa infektioner kan inte behandlas med stafylokock-penicilliner och MRSA-bakterierna är ofta resistenta även mot flera andra grupper av antibiotika vilket medför att infektionerna ofta är påtagligt svårbehandlade. Under senare år har emellertid allt fler fall beskrivits av samhällsförvärvad MRSA infektion, det vill säga uppträdande av MRSA hos personer som tidigare ej har haft kontakt med sjukhusvård eller behandlats med antibiotika. Det har länge varit oklart om de samhällsförvärvade MRSA [community-acquired (CA-MRSA)] representerar spridning av bakterier från sjukhusmiljön ut till samhället eller om dessa MRSA är spontant uppträdande. Många av dessa stammar har dessutom visat sig bära på sjukdomsrelaterade gener som vanligen inte återfinns hos S. aureus, t.ex. Panton Valentine leukocidin (PVL) som associeras med hudinfektioner och allvarlig lunginflammation med hög dödlighet hos unga och annars friska individer.

Denna avhandling beskriver den molekylära epidemiologin hos MRSA med fokus på samhällsförvärvade MRSA som utgjorde mer än hälften av samtliga fall av MRSA i Örebro län och som dessutom ofta producerade PVL toxinet, vars funktion vidare analyserades i detalj. Undersökning av ursprung och släktskap hos samtliga MRSA som isolerats i Örebro län, samt karaktärisering av det genetiskt element som kallas staphylococcal cassette chromosome mec (SCCmec) vilket innehåller genen mecA och ibland även andra resistensgener, visade att CA-MRSA inte är relaterade till de nosokomiala MRSA, och att dessa har uppstått oberoende av varandra. Flertalet MRSA visade sig dessutom bära på SCCmec, och resistensmekanismer, som tidigare inte beskrivits. Troligen har dessa MRSA uppstått genom ett genetiskt utbyte av SCCmec mellan methicillin-resistenta koagulas-negativa stafylokocker (MR-KNS), som utgör huvudparten av normalfloran på huden, och methicillin-känsliga S. aureus som därvid erhåller genen mecA och resistensmekanismer mot samtliga stafylokockantibiotika. I den här avhandlingen framläggs bevis för att ett sådant genetiskt utbyte har skett på Barnkliniken på Universitetssjukhuset i Örebro i slutet på 1990-talet, vilket resulterade i uppkomsten av en ny klon av MRSA som därefter orsakade ett allvarligt utbrott. Kartläggning av DNA-sekvensen hos flertalet unika SCCmec från svenska MRSA gav dessutom en bättre förståelse för hur resistens uppkommer och sprider sig, samt mekanismerna bakom detta. Dessa nya kunskaper kan bidra till en förbättrad diagnostik av MRSA. Detta är framför allt av stor betydelse eftersom nya effektiva kloner av MRSA verkar kunna uppstå ute i samhället med potential att orsaka svårbehandlade infektioner men även att sprida sig bland den friska befolkningen.

Abstract [en]

Material and methods - During a period of 14 years, around 2000 patients with head injuries were admitted to the emergency ward at Lindesberg County Hospital and Örebro Medical Centre Hospital. Six hundred subjects suffered from skull fracture and/or brain contusion and diagnosis was established using a computed tomography scan (CT). The degree of initial brain injury was estimated using the Swedish Reaction Level Scale (RLS). Sixty-six subjects were investigated with pure tone audiometry in close proximity to the trauma, and this gave an opportunity to study the issue of progress. The investigation took place two to 14 years after trauma, and the results were compared to matched control groups. A battery of different audiological methods was used to investigate peripheral and central auditory function, and a specially designed acoustic environmental room was also utilized. Cognition was investigated using a computer-based test-battery, text information process system (TIPS). Self-assessed hearing, cognition and quality of life were explored using different questionnaires.

Results - A high percentage of peripheral and central auditory impairments and also cognitive shortcomings were demonstrated. Progress of SNHL was a common finding, and fracture, high age at trauma and large initial hearing loss predicted progress. Antibody-mediated autoimmunity as a mechanism behind posttraumatic progress of SNHL or clear evidence for sympathetic cochleolabyrinthitis could not be demonstrated. Binaural auditory deficits could be demonstrated when tested in a realistic acoustic environment. Tinnitus, vertigo and memory shortcomings proved to be common sequelae, even in a long-term perspectiveCognitive shortcomings were found in several of these well-rehabilitated subjects.On a group level, there was a good correlation between self-assessments and audiometric results, even if some individuals had a tendency to over- or underestimate their abilities.

Conclusion - Auditory and cognitive long-term sequelae of CHI are a common finding even in well-rehabilitated and socially well-functioning subjects, as are vertigo and tinnitus. Vertigo and tinnitus are also common sequelae after CHI, therefore a basic audiovestibular investigation after CHI is recommended, at least in selected cases.Early awareness of the risk for hearing and cognitive sequelae after CHI could lead to measurements taken to prevent tension-related symptoms.Early detection of HI offers an opportunity to try immunosuppressive treatment in cases with a large initial SNHL.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2008. p. 126
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 20
Keywords
methicillin-resistant Staphylococcus aureus (MRSA), community-acquired MRSA (CA-MRSA), staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing (MLST), horizontal transfer, Panton Valentine leukocidin (PVL)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-2443 (URN)978-91-7668-611-9 (ISBN)
Public defence
2008-09-26, Wilandersalen, Universitetssjukhuset Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2008-09-02 Created: 2008-09-02 Last updated: 2017-10-18Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=18656408&dopt=Citation

Authority records BETA

Berglund, CarolinaSöderquist, Bo

Search in DiVA

By author/editor
Berglund, CarolinaSöderquist, Bo
By organisation
School of Health and Medical Sciences
In the same journal
Microbes and infection
Medical and Health SciencesMicrobiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 426 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf