Evolutionary Models of the Emergence ofMethicillin-Resistant Staphylococcusaureus

Abstract

ABSTRACT Five major lineages of methicillin-resistant Staphylococcus aureus (MRSA) have evolved since the introduction of methicillin for the treatment of infections caused by penicillin-resistant S. aureus in 1959. The clones of these lineages are responsible for the vast majority of hospital-acquired MRSA disease globally. We have constructed high-resolution evolutionary models for each lineage using a parsimony approach with 15 partial gene sequences from 147 geographically diverse isolates. On the basis of these models, we infer that MRSA has emerged at least 20 times upon acquisition of the methicillin resistance determinant, which is carried on a mobile genetic element called the staphylococcal cassette chromosome mec (SCC mec ). The acquisition of SCC mec by sensitive clones was four times more common than the replacement of one SCC mec with another. Notably, SCC mec type IV was found in twice as many clones as any other SCC mec type, and it is this SCC mec type which is commonly found in clones from patients with community-acquired MRSA disease. Our findings suggest that most clones of MRSA arise by the acquisition of SCC mec type IV by methicillin-sensitive isolates.