title: Identifying the effect of patient sharing on between-hospital genetic differentiation of methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common healthcare-associated pathogens. To examine the role of inter-hospital patient sharing on MRSA transmission, a previous study collected 2,214 samples from 30 hospitals in Orange County, California and showed by spa typing that genetic differentiation decreased significantly with increased patient sharing. In the current study, we focused on the 986 samples with spa type t008 from the same population.
  
  
  METHODS
  We used genome sequencing to determine the effect of patient sharing on genetic differentiation between hospitals. Genetic differentiation was measured by between-hospital genetic diversity, F ST , and the proportion of nearly identical isolates between hospitals.
  
  
  RESULTS
  Surprisingly, we found very similar genetic diversity within and between hospitals, and no significant association between patient sharing and genetic differentiation measured by F ST . However, in contrast to F ST , there was a significant association between patient sharing and the proportion of nearly identical isolates between hospitals. We propose that the proportion of nearly identical isolates is more powerful at determining transmission dynamics than traditional estimators of genetic differentiation (F ST ) when gene flow between populations is high, since it is more responsive to recent transmission events. Our hypothesis was supported by the results from coalescent simulations.
  
  
  CONCLUSIONS
  Our results suggested that there was a high level of gene flow between hospitals facilitated by patient sharing, and that the proportion of nearly identical isolates is more sensitive to population structure than F ST when gene flow is high.
authors.affiliation: Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. hhchang@hsph.harvard.edu.
authors.forename: Hsiao-Han
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK. jd3234@drexel.edu.|Department of Biology, Drexel University, Philadelphia, PA, USA. jd3234@drexel.edu.
authors.forename: Janina
authors.initials: J
authors.lastname: Dordel
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, UK. tjibbe.donker@ndm.ox.ac.uk.
authors.forename: Tjibbe
authors.initials: T
authors.lastname: Donker
authors.affiliation: Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. cworby@hsph.harvard.edu.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Worby
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK. E.Feil@bath.ac.uk.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.affiliation: Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. whanage@hsph.harvard.edu.
authors.forename: William P
authors.initials: WP
authors.lastname: Hanage
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK. sdb@sanger.ac.uk.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Division of Infectious Diseases and Health Policy Research Institute, University of California Irvine School of Medicine, Irvine, CA, USA. sshuang@uci.edu.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. mlipsitc@hsph.harvard.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
mesh_terms: D002140:California / Q000453:epidemiology; D003198:Computer Simulation; D003428:Cross Infection / Q000382:microbiology / Q000635:transmission*; D051456:Gene Flow; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000635:transmission*