Range Expansion and the Origin of USA300 North American Epidemic Methicillin-Resistant <italic toggle="yes">Staphylococcus aureus</italic>
Lavanya Challagundla,
Xiao Luo,
Isabella A. Tickler,
Xavier Didelot,
David C. Coleman,
Anna C. Shore,
Geoffrey W. Coombs,
Daniel O. Sordelli,
Eric L. Brown,
Robert Skov,
Anders Rhod Larsen,
Jinnethe Reyes,
Iraida E. Robledo,
Guillermo J. Vazquez,
Raul Rivera,
Paul D. Fey,
Kurt Stevenson,
Shu-Hua Wang,
Barry N. Kreiswirth,
Jose R. Mediavilla,
Cesar A. Arias,
Paul J. Planet,
Rathel L. Nolan,
Fred C. Tenover,
Richard V. Goering,
D. Ashley Robinson
Affiliations
Lavanya Challagundla
Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA
Xiao Luo
Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA
Isabella A. Tickler
Cepheid, Sunnyvale, California, USA
Xavier Didelot
Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
David C. Coleman
Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland
Anna C. Shore
Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland
Geoffrey W. Coombs
School of Veterinary and Life Sciences, Murdoch University, Perth, Australia
Daniel O. Sordelli
Instituto de Investigaciones en Microbiología y Parasitología Médica, Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina
Eric L. Brown
Center for Infectious Diseases, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center, Houston, Texas, USA
Robert Skov
Statens Serum Institut, Copenhagen, Denmark
Anders Rhod Larsen
Statens Serum Institut, Copenhagen, Denmark
Jinnethe Reyes
Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia
Iraida E. Robledo
Department of Microbiology and Medical Zoology, University of Puerto Rico, San Juan, Puerto Rico
Guillermo J. Vazquez
Department of Microbiology and Medical Zoology, University of Puerto Rico, San Juan, Puerto Rico
Raul Rivera
Department of Microbiology and Medical Zoology, University of Puerto Rico, San Juan, Puerto Rico
Paul D. Fey
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
Kurt Stevenson
Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA
Shu-Hua Wang
Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA
Barry N. Kreiswirth
Public Health Research Institute of New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
Jose R. Mediavilla
Public Health Research Institute of New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
Cesar A. Arias
Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia
Paul J. Planet
Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Rathel L. Nolan
Department of Internal Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi, USA
Fred C. Tenover
Cepheid, Sunnyvale, California, USA
Richard V. Goering
Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, USA
D. Ashley Robinson
Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA
ABSTRACT The USA300 North American epidemic (USA300-NAE) clone of methicillin-resistant Staphylococcus aureus has caused a wave of severe skin and soft tissue infections in the United States since it emerged in the early 2000s, but its geographic origin is obscure. Here we use the population genomic signatures expected from the serial founder effects of a geographic range expansion to infer the origin of USA300-NAE and identify polymorphisms associated with its spread. Genome sequences from 357 isolates from 22 U.S. states and territories and seven other countries are compared. We observe two significant signatures of range expansion, including decreases in genetic diversity and increases in derived allele frequency with geographic distance from the Pennsylvania region. These signatures account for approximately half of the core nucleotide variation of this clone, occur genome wide, and are robust to heterogeneity in temporal sampling of isolates, human population density, and recombination detection methods. The potential for positive selection of a gyrA fluoroquinolone resistance allele and several intergenic regions, along with a 2.4 times higher recombination rate in a resistant subclade, is noted. These results are the first to show a pattern of genetic variation that is consistent with a range expansion of an epidemic bacterial clone, and they highlight a rarely considered but potentially common mechanism by which genetic drift may profoundly influence bacterial genetic variation. IMPORTANCE The process of geographic spread of an origin population by a series of smaller populations can result in distinctive patterns of genetic variation. We detect these patterns for the first time with an epidemic bacterial clone and use them to uncover the clone’s geographic origin and variants associated with its spread. We study the USA300 clone of methicillin-resistant Staphylococcus aureus, which was first noticed in the early 2000s and subsequently became the leading cause of skin and soft tissue infections in the United States. The eastern United States is the most likely origin of epidemic USA300. Relatively few variants, which include an antibiotic resistance mutation, have persisted during this clone’s spread. Our study suggests that an early chapter in the genetic history of this epidemic bacterial clone was greatly influenced by random subsampling of isolates during the clone’s geographic spread.
