Molecular epidemiology of community-acquired methicillin resistant Staphylococcus aureus

Staphylococcus aureus causes many infection types, ranging in severity from superficial cutaneous abscess to life-threatening septicemia and pneumonia. The introduction of penicillin and beta-lactamase stable penicillins, although dramatically improved management of staphylococcal infections, also selected for methicillin-resistant strains of S. aureus (MRSA). The original MRSA clones belonged to five distinct clonal lineages, and have spread in hospitals worldwide. Recently, other MRSA clones became established in the community. It is not clear why certain MRSA clones predominate in the hospital and other MRSA clones predominate in the community. My dissertation research had contributed to a better understanding of the epidemiological and molecular forces affecting variations in MRSA disease frequency and disease severity. This work began with the development of rapid, low-cost molecular markers for the epidemiologic tracking of MRSA strains. Genetic characterizations of MRSA isolates commenced rapidly after the proof of concept, enabling the critical evaluation of several research hypotheses. First, we hypothesized that CA-MRSA and HA-MRSA are genetically and epidemiologically unrelated, which directly challenged the traditional view that CA-MRSA are feral escapees from the hospital reservoir. The results of this study not only demonstrated that CA-MRSA and HA-MRSA are biologically different but also advanced the notion that CA-MRSA are adapted for a community lifestyle. Second, we hypothesized that the population dynamics of CA-MRSA strains and their disease activity in community settings are dependent on the population dynamics of nasal strains of CA-MRSA. Indeed, we identified three population dynamics relating MRSA nasal colonization and disease activity: (i) endemic clones that sustained asymptomatic carriage and infections over prolonged periods; (ii) an epidemic clone that demonstrated enhanced capacity for rapid transmission and widespread infections; and (iii) an outbreak clone that was highly infectious but exhibited poor asymptomatic transmission. Third, we hypothesized that variations in virulence gene content and allelic diversity contribute to MRSA lineage diversification, epidemiological characters, and disease pathogenesis (submitted). To test this hypothesis, we have assessed the role of 34 virulence determinants and SCCmec allotypes in inpatient and outpatient MRSA isolates collected over 8.5 years through laboratory-based surveillance in San Francisco. The study revealed evolutionary patterns of descent that explain the recent emergence of epidemic CA-MRSA strains. (Abstract shortened by UMI.)...