Phylogeographical analysis reveals the historic origin, emergence, and evolutionary dynamics of methicillin-resistant Staphylococcus aureus ST228

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a common healthcare-associated pathogen that remains a major public health concern. Sequence type 228 (ST228) was first described in Germany and represented a successful MRSA clone in several European countries. Since 2000, ST228 had emerged in Lausanne causing several large outbreaks. Here, we aimed to elucidate the evolutionary history of this clone and to determine the genetic contents correlating with its expansion and successful spread in Switzerland.Materials/methods: We elucidated the phylogeographical structure and demographic expansion of ST228/ST111 by sequencing 530 MRSA isolates that were collected from 14 European countries between 1997 and 2012.Results: The phylogenetic analysis revealed that clades of ST228 isolates were associated with their geographical origin, while isolates of ST111 (a single locus variant of ST228 sharing the same spa type 041) from different countries composed a distinct clade. Furthermore, the European ST228 population originated from a distinct German lineage characterized by spa type t001. The highly successful Swiss ST228 lineage was associated with the loss of aminoglycoside-streptothricin resistance gene cluster and the gain of mupirocin resistance. This lineage was introduced first in Geneva and, subsequently, emerged in Lausanne on several occasions. Conclusions: Our results suggest that several ST228 lineages evolved from its progenitor in Germany and emerged into different European countries. In Switzerland, ST228 was introduced first in Geneva and, subsequently, spread in Lausanne. Additional reads files are found in ENA under the accessory number PRJEB34139 (The role of asymptomatic enteric carriage in maintaining a long-term hospital outbreak of ST228 methicillin resistant Staphylococcus aureus)