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Large-scale evaluation of bacterial genome content for the identification of epidemiological and virulence basis in MRSA

English title Large-scale evaluation of bacterial genome content for the identification of epidemiological and virulence basis in MRSA
Applicant François Patrice
Number 116075
Funding scheme Project funding (Div. I-III)
Research institution Laboratoire de Recherche Génomique Service des Maladies Infectieuses Hôpital Cantonal - HUG
Institution of higher education University of Geneva - GE
Main discipline Medical Microbiology
Start/End 01.05.2007 - 30.04.2010
Approved amount 227'000.00
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Keywords (6)

Staphylococcus aureus; MRSA; genomic content; mutations; insertions; deletions

Lay Summary (English)

Lead
Lay summary
Despite continuous progress in the medical and diagnostic fields, Staphylococcus aureus (S. aureus) remains a major bacterial pathogen involved in a wide spectrum of diseases ranging from benign skin infections to severe diseases such as endocarditis or septicemia. S. aureus colonizes the nares in 20-30% of the general population without causing any clinical manifestation, but it remains a versatile and dangerous pathogen for humans. The emergence of antimicrobial resistance in S. aureus has restricted the efficacy of most drug classes. For example, S. aureus resistant against methicillin (MRSA) is commonly identified in several countries (in Europe, United States, Japan), and requires the utilization of last barrier drugs, such as glycopeptides. Control of such infections requires expensive surveillance programs including patient isolation and contact precautions, with considerable impact on costs.Until recently, S. aureus was considered as the prototype of nosocomial pathogen but it has now clearly shown also responsible for outbreaks in the community. Several reports suggest that the epidemiology of MRSA is changing. The understanding of pathogenicity, virulence and emergence of epidemic clones within MRSA populations is not clearly defined, despite several attempts to identify common molecular features between strains sharing similar epidemiological and/or virulence behavior. We hypothesize that parameters contributing to strain virulence or invasiveness are contained within the genetic material of strains, i.e. in their genome. Our study is based on the utilization of massively parallel methods of analysis, including whole genome sequencing and microarrays, to study the contribution of this genetic make-up. By using bio-informatics and molecular tools, we plan to identify punctual differences at the genome scale potentially related to specific behavior of clinical isolates. Whole genomes will be studied using microarrays covering not only all the genes of the bacterium but also the totality of the intergenic regions. Strain collections will be identified by benefiting from previous works performed in our laboratory.Overall, this proposal will contribute to evaluate common features among strain populations, in correlation with their defense and growth capacity. Ideally these determinations will allow appreciating micro and macro evolution of MRSA and identifying specific genomic markers of evolution towards invasive or highly virulent phenotypes.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
121418 Ultra High Throughput sequencing platform for functional genome analysis 01.08.2008 R'EQUIP

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