Objectives: A small number of clones are responsible for the majority of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) infections globally. One such clone is the multi-locus sequence type (ST) 239; a multidrug-resistant, hybrid clone of MRSA that has dominated the global hospital environment since it was first reported in the 1970s. Currently very little is known about the evolution of ST239 MRSA in Australia; a geographically distinct region where this clone has predominated in the hospital environment for nearly 40 years.
Methods: To explore the evolution of ST239, whole genome sequencing and phenotypic analysis was performed on 87 strains recovered from Australia between 1980 to 2012. The genome sequences of a further 36 international ST239 strains were also included. Bayesian phylogenetic inference was used to establish a model for the population structure of ST239 based on these 123 genomes. A pan-genome was generated to examine accesory gene content amongst Australian ST239 strains. Their phenotypic evolution was also explored by analysing changes in antimicrobial phenotypes, growth characteristics and virulence capability over time.
Results: The phylogenetic model showed concurrent and independent evolution of two deep-branching ST239 sub-clones in Australia. One lineage appears to be the original clone in this region, whereas the other represents a re-introduction of ST239 into the state of Victoria that is phylogenetically similar to ST239 strains of Asian origin. The phenotypic evolution of Australian ST239 MRSA appears to be one of decreasing susceptibility to the glycopeptides and daptomycin but also attenuated virulence, with a loss of activity in the accessory gene regulator (agr) that is not always associated with agr mutations.
Conclusion: There has been concurrent evolution of two distinct lineages of ST239 MRSA in Australia over the past 30 years, both leading independently to enhanced antimicrobial resistance and attenuated virulence.