Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial infection. Whole-genome sequencing of MRSA has been used to define phylogeny and transmission in well-resourced healthcare settings, yet the greatest burden of nosocomial infection occurs in resource-restricted settings where barriers to transmission are lower. Here, we study the flux and genetic diversity of MRSA on ward and individual patient levels in a hospital where transmission was common. We repeatedly screened all patients on two intensive care units for MRSA carriage over a 3-mo period. All MRSA belonged to multilocus sequence type 239 (ST 239). We defined the population structure and charted the spread of MRSA by sequencing 79 isolates from 46 patients and five members of staff, including the first MRSA-positive screen isolates and up to two repeat isolates where available. Phylogenetic analysis identified a flux of distinct ST 239 clades over time in each intensive care unit. In total, five main clades were identified, which varied in the carriage of plasmids encoding antiseptic and antimicrobial resistance determinants. Sequence data confirmed intra-and interwards transmission events and identified individual patients who were colonized by more than one clade. One patient on each unit was the source of numerous transmission events, and deep sampling of one of these cases demonstrated colonization with a ''cloud'' of related MRSA variants. The application of whole-genome sequencing and analysis provides novel insights into the transmission of MRSA in under-resourced healthcare settings and has relevance to wider global health.

Next-Generation Sequencing Confirms Presumed Nosocomial Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in the Netherlands

“…However, it obviously belonged to the outbreak, suggesting that an LA-MRSA strain colonizing or infecting different sites within the same person may evolve independently over time. Recent reports that applied whole-genome sequencing on multiple colonies from the same person also identified a cloud of diversity among the isolates (21,34,35). These studies were carried out on ST22 and ST239 MRSA isolates, but similar findings might be expected from LA-MRSA.…”

Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation

“…We postulate that the existence of a significant cloud of diversity (4, 12) may be a marker of long-term carriage. Therefore, in outbreaks, higher diversity may indicate the involvement of an LTC, with outbreak diversity reflecting the donor cloud.…”

Livestock-Associated Methicillin Resistant Staphylococcus aureus (LA-MRSA) Clonal Complex (CC) 398 Isolated from UK Animals belong to European Lineages

“…Also, WGS and downstream applications are increasingly being applied to pathotype microorganisms, to provide a view on the epidemiology, phylogeny and microevolution of bacterial pathogens; including MRSA (Fitzgerald, 2012; Price et al, 2012; Tong et al, 2015). Advances in comparative genomics, using WGS, allows for a more rapid and accurate method to determine phylogenetic relationships between groups of isolates compared to more traditional typing and screening methods such as MLST and DNA microarray.…”