Origin and Evolution of the European Community-Acquired Methicillin-Resistant Staphylococcus aureus

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages emerged around the world carrying the small SCCmec types IV and V genetic elements and the Panton-Valentine leukocidin (PVL). In Europe, the predominant CA-MRSA belongs to clonal complex (CC) 80 and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993, but was relatively rare until the late 1990s. It has since then been described throughout of Northern Africa, the Middle East and Europe, with recent sporadic reports in Sub-Saharan Africa. While strongly associated with skin and soft-tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 are extremely rare except in Sub-Saharan Africa. In the current study, we applied whole genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from Sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and of a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a non-synonymous mutation in the accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East and Northern Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.