Population structure of a hybrid clonal group of methicillin-resistant Staphylococcus aureus, ST239-MRSA-III

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 100x 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.

Figure 1. Evolutionary relationships within the ST239 clonal group.

Tree is the most parsimonious haplotype tree found by heuristic search. Haplotypes are numbered H1–H28. Circles represent the number of isolates of each haplotype. Names of important strains are indicated in parentheses below select haplotypes. Blue labels indicate the discovery panel of isolates. Numbers along branches are bootstrap proportions. Three prominent clades are highlighted.

Figure 2. Geographic structure within the ST239 clonal group.

Tree is a neighbor-joining population tree based on the average number of pairwise nucleotide differences between countries. Labels are colored according to continents.

Figure 3. Homoplasy among SCCmec type III variants.

(A) Mapping of SCCmec multiplex PCR types onto the haplotype tree of Figure 1. (B) Mapping of SCCmec ccrB:dru sequence types onto the haplotype tree of Figure 1. Red highlights homoplasy where two SCCmec subtypes occur together in more than one haplotype.