Evolution of MRSA during hospital transmission and intercontinental spread

Abstract

Current methods for differentiating isolates of predominant lineages of pathogenic bacteria often do not provide sufficient resolution to define precise relationships. Here, we describe a high-throughput genomics approach that provides a high-resolution view of the epidemiology and microevolution of a dominant strain of methicillin-resistant Staphylococcus aureus (MRSA). This approach reveals the global geographic structure within the lineage, its intercontinental transmission through four decades, and the potential to trace person-to-person transmission within a hospital environment. The ability to interrogate and resolve bacterial populations is applicable to a range of infectious diseases, as well as microbial ecology.

Fig. 1

Phylogenetic evidence for intercontinental spread and hospital transmission of ST239 isolates. Maximum likelihood phylogenetic tree based on core genome SNPs of ST239 isolates, annotated with the country and year of isolation. The continental origin of each isolate is indicated by the color of the isolate name: blue, Asia; black, North America; green, South America; red, Europe; and yellow, Australasia. Bootstrap values are shown below each branch, with a star representing 100% bootstrap support. The scale bar represents substitutions per SNP site. A cladogram of the Thai clade is displayed for greater resolution with bootstrap values (above the branch), number of distinguishing SNPs (below the branch), and isolates labeled with date of isolation, where known.

Fig. 2

Comparison of phylogeny with traditional typing techniques. Maximum likelihood phylogenetic tree based on core genome SNPs of ST239 isolates, annotated with spa typing databased on the RIDOM scheme (27), and PFGE typing databased on BioNumerics (version 4.0, Applied Maths, Ghent, Belgium) clustering (excluding the Thai hospital isolates and USA300, which had not been typed). The most common spa type was t037, which accounted for all but one of the isolates corresponding to the South American clade but was also represented among a scattering of isolates from Europe and Asia, suggesting that t037 represents the ancestral ST239 spa type (the plesiomorphic state). Solid boxes in the appropriate column indicate the respective spa type (left grid) and PFGE cluster (right grid) of the strain. Major clades in the tree are shaded for clarity.