Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
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 use 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 a wide range 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.
Data availability
Illumina read data is available in the European Nucleotide Archive as part of study accession number PRJEB4140. Genome assemblies will be made available prior to publication. We are unable to provide patient data for reasons of confidentiality.
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Staphylococcus aureus ST239 diversity in ThailandEuropean Nucleotide Archive, PRJEB4140.
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Evolution of MRSA During Hospital Transmission and Intercontinental SpreadEuropean Nucleotide Archive, PRJEB2489.
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Staphylococcus aureus ST239 diversityEuropean Nucleotide Archive, PRJEB2076.
Article and author information
Author details
Funding
Wellcome (098051)
- Matthew TG Holden
- Sharon J Peacock
Chief Scientist Office (SIRN10)
- Matthew TG Holden
Wellcome (106698/Z/14/Z)
- Vanaporn Wuthiekanun
Medical Research Council (G1000803)
- Sharon J Peacock
European Research Council (PBDR-339251)
- Matthew D Hall
- Christophe Fraser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethical approval was obtained from the Ethical and Scientific Review subcommittee of the Royal Thai Government Ministry of Public Health (85/2550), and the Oxford Tropical Research Ethics Committee (024 07). All patients admitted to the two ICUs were eligible for inclusion and were enrolled after written informed consent, and consent to publish, was obtained.
Copyright
© 2019, Hall et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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