Rapid characterization and molecular epidemiology of methicillin resistant Staphylococcus aureus - a prevalence study in distinct populations
This proposal combines molecular biology development and epidemiology with five major objectives:
1) Development of molecular genotyping and virulence prediction assays
2) Validation of these assays using previously characterized isolates
3) Determination of MRSA prevalence in distinct population groups and different geographical areas
4) Detection of virulence genes in MRSA from colonization and infection episodes
The project will help answering a number of important questions. Prevalence rates of MRSA are believed to be dependant on a number of biodemographical factors as well as geographic origin. It is well known that a prevalence gradient exists from North to South in Switzerland. Although Northern Switzerland is surrounded by high-prevalence countries (France and Germany), we do not find as high rates as in the South, which is surrounded by the high-prevalence countries France and Italy. The question whether CA-MRSA originates oligoclonally in the general population or is spread through discharge of unrecognized colonized patients from hospitals, will be addressed by the findings of the study. These new assays will allow to rapidly establish relationship of isolates and presence of significant virulence factors to improve identification of patients who would benefit from eradication as opposed to patients carrying a "benign" strain. Currently, MRSA is detected by conventional microbiological methods and PFGE is considered a gold standard for molecular typing. With the large-scale application of PCR as a rapid diagnostic tool for both detection and typing, we will validate our method and assess its sensitivity and specificity. With the expected better diagnostic accuracy, cost may be outweighed by performance indicators. When validated, this approach should enable future prevalence projects to be conducted in shorter time. This rapid assay will be used to determine the origin of community-acquired MRSA. By mapping the clonal distribution of MRSA in distinct populations, we will evaluate the role of migration and mobility in the spreading of resistant pathogens. The link between carriage rates in the general population and resistance in hospitals will be answered, and therefore will be used to evaluate population-based interventions. Finally, new molecular methods will be applied to broader use, benefiting from traditional microbiology and modern genomics.