title: Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration.
abstract: Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance.
  
  
  
  Unlike methicillin-resistant Staphylococcus aureus (MRSA), surprisingly little is known about the clonal evolution of methicillin-susceptible S. aureus (MSSA), although these strains account for the majority of S. aureus infections. To better understand how MSSA spreads and becomes established in communities, we applied comparative bacterial whole-genome sequencing to pandemic ST398-MSSA, a clone of clinical importance affecting humans and livestock in different geographic regions. Phylogeographic analyses identified that ST398-MSSA spread along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. We observed high within-host SNP variability compared to our previous studies on the dominant MRSA clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300 MRSA and ST398 MSSA.
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, USA au2110@columbia.edu.
authors.forename: Anne-Catrin
authors.initials: AC
authors.lastname: Uhlemann
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom.|Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: McAdam
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Sullivan
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Knox
authors.affiliation: Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, USA.|Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Khiabanian
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
authors.affiliation: Department of Veterinary Population Medicine, University of Minnesota, St. Paul, Minnesota, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Davies
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, USA.|Department of Pathology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Franklin D
authors.initials: FD
authors.lastname: Lowy
mesh_terms: D000818:Animals; D018562:Disease Transmission, Infectious; D014644:Genetic Variation; D005838:Genotype; D014943:Global Health; D063426:Human Migration; D006801:Humans; D017720:Molecular Epidemiology; D058873:Pandemics; D058974:Phylogeography; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission / Q000662:veterinary*; D013211:Staphylococcus aureus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification