Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

• Published in: eLife Vol. 8
• Main Authors: Hall, Matthew D, Holden, Matthew TG, Srisomang, Pramot, Mahavanakul, Weera, Wuthiekanun, Vanaporn, Limmathurotsakul, Direk, Fountain, Kay, Parkhill, Julian, Nickerson, Emma K, Peacock, Sharon J, Fraser, Christophe
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 08.10.2019; eLife Sciences Publications, Ltd
• Subjects: Adult; Child; Computational Biology - methods; Cross Infection - microbiology; Cross Infection - transmission; Disease Outbreaks; Disease transmission; DNA, Bacterial - genetics; Drug resistance; Epidemiology; Epidemiology and Global Health; Genetic diversity; Genetic Variation; Genome, Bacterial - genetics; Genomes; hospital infections; Humans; Intensive care; Methicillin; Methicillin-Resistant Staphylococcus aureus - classification; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - physiology; molecular epidemiology; MRSA; Pathogens; Patients; Phylogenetics; Phylogeny; Polymorphism, Single Nucleotide; Single-nucleotide polymorphism; Staphylococcal Infections - epidemiology; Staphylococcal Infections - microbiology; Staphylococcal Infections - transmission; Staphylococcus aureus; Staphylococcus infections; Thailand - epidemiology; Whole Genome Sequencing - methods; Thailand; global health; molecular epidemiology; epidemiology; hospital infections; human; MRSA
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.46402

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.