Origin, evolution, and global transmission of community-acquired <i>Staphylococcus aureus</i> ST8

Abstract

USA300 is a pandemic clonal lineage of hypervirulent, community-acquired, methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA) with specific molecular characteristics. Despite its high clinical relevance, the evolutionary origin of USA300 remained unclear. We used comparative genomics of 224 temporal and spatial diverse <i>S. aureus</i> isolates of multilocus sequence type (ST) 8 to reconstruct the molecular evolution and global dissemination of ST8, including USA300. Analyses of core SNP diversity and accessory genome variations showed that the ancestor of all ST8 <i>S. aureus</i> most likely emerged in Central Europe in the mid-19th century. From here, ST8 was exported to North America in the early 20th century and progressively acquired the USA300 characteristics Panton-Valentine leukocidin (PVL), SCC<i>mec</i> IVa, the arginine catabolic mobile element (ACME), and a specific mutation in capsular polysaccharide gene <i>cap5E</i> Although the PVL-encoding phage ϕSa2USA was introduced into the ST8 background only once, various SCC<i>mec</i> types were introduced to ST8 at different times and places. Starting from North America, USA300 spread globally, including Africa. African USA300 isolates have aberrant <i>spa</i>-types (t112, t121) and form a monophyletic group within the clade of North American USA300. Large parts of ST8 methicillin-susceptible <i>S. aureus</i> (MSSA) isolated in Africa represent a symplesiomorphic group of ST8 (i.e., a group representing the characteristics of the ancestor), which are rarely found in other world regions. Isolates previously discussed as USA300 ancestors, including USA500 and a "historic" CA-MRSA from Western Australia, were shown to be only distantly related to recent USA300 clones.