title: 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.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; Menzies School of Health Research, Darwin, Northern Territory 0811, Australia;
authors.forename: Steven Y C
authors.initials: SY
authors.lastname: Tong
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.affiliation: Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Emma K
authors.initials: EK
authors.lastname: Nickerson
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
authors.forename: Ben S
authors.initials: BS
authors.lastname: Cooper
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 OXY, United Kingdom; Public Health England, Cambridge CB2 0QW, United Kingdom;
authors.forename: Claudio U
authors.initials: CU
authors.lastname: Köser
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Cori
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Jombart
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Cauchemez
authors.affiliation: Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
authors.forename: Vanaporn
authors.initials: V
authors.lastname: Wuthiekanun
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
authors.forename: Janjira
authors.initials: J
authors.lastname: Thaipadungpanit
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
authors.forename: Maliwan
authors.initials: M
authors.lastname: Hongsuwan
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Day
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
authors.forename: Direk
authors.initials: D
authors.lastname: Limmathurotsakul
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand; Department of Medicine, University of Cambridge, Cambridge CB2 OXY, United Kingdom; Public Health England, Cambridge CB2 0QW, United Kingdom;
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D000328:Adult; D015373:Bacterial Typing Techniques; D002648:Child; D019295:Computational Biology; D003428:Cross Infection / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics; D004196:Disease Outbreaks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016014:Linear Models; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology
chemical_list: D004269:DNA, Bacterial