Abstract
The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100× faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec.
Highlights
As one of the most common antibiotic-resistant bacterial pathogens, methicillin-resistant Staphylococcus aureus (MRSA) pose immense challenges to healthcare systems throughout the world [1]
Decades of molecular epidemiological studies suggest that the hybrid MRSA clonal group, ST239, has spawned multiple globally disseminated variants that occur with a single staphylococcal chromosomal cassette mec (SCCmec) type
Since no homoplasy was observed at the 32 loci, the data indicated that ST239 has diversified clonally via point mutations
Summary
As one of the most common antibiotic-resistant bacterial pathogens, methicillin-resistant Staphylococcus aureus (MRSA) pose immense challenges to healthcare systems throughout the world [1]. Studies have provided a coarse outline of the population structure of this pathogen [2,3,4]. Five clonal groups have spawned the majority of nosocomial MRSA that are isolated worldwide, and they can be readily identified by their founding multilocus sequence types (ST): ST5, ST8, ST22, ST30, and ST45 [2]. It was deduced that the staphylococcal chromosomal cassette mec (SCCmec) genetic element, which confers the methicillin resistance phenotype [5], has been horizontally transferred into these five clonal groups on many occasions, giving rise to numerous individual MRSA clones [6,7]. Decades of molecular epidemiological studies suggest that the hybrid MRSA clonal group, ST239, has spawned multiple globally disseminated variants that occur with a single SCCmec type.
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