Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we used a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding considerable variation in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted.
Highlights
Whole-genome sequencing (WGS) has proved a valuable tool in the investigation of the transmission of infectious agents
Consenting patients admitted to two intensive care units (ICUs) at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand, during a period of three months in 2008 were recruited
We investigated the size of the bottleneck at transmission for six pairs of colonisations in detail. (By ‘bottleneck’ we refer to the total number of genetic lineages passed from one colonisation to another; in this study we cannot differentiate between multiple lineage transmission at a single time point and the transmission of multiple single lineages at different points.) All six had a reconstructed transition in one or both directions in 95% of posterior trees, and, in the subgraphs involved in those transmissions, a posterior median of at least five tips in those belonging to the recipient
Summary
Whole-genome sequencing (WGS) has proved a valuable tool in the investigation of the transmission of infectious agents. The focus of previous studies has ranged from identifying bacterial spread between continents (Harris et al, 2010), to reconstructing the detailed timelines of outbreaks in single hospital wards (Koser et al, 2012; Harris et al, 2013). Several prospective studies have been conducted in single settings (Price et al, 2014; Nubel et al, 2013). In a previous study, Tong et al (2015) acquired and sequenced MRSA isolates from the hightransmission setting of two intensive care units (ICUs) in a Thai hospital. All were of sequence type 239 (ST 239). They showed that bacterial genetic diversity in this single location provided evidence
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