title: Full-genome dissection of an epidemic of severe invasive disease caused by a hypervirulent, recently emerged clone of group A Streptococcus.
abstract: Group A Streptococcus (GAS) causes an exceptionally broad range of infections in humans, from relatively mild pharyngitis and skin infections to life-threatening necrotizing fasciitis and toxic shock syndrome. An epidemic of severe invasive human infections caused by type emm59 GAS, heretofore an exceedingly rare cause of disease, spread west to east across Canada over a 3-year period (2006 to 2008). By sequencing the genomes of 601 epidemic, historic, and other emm59 organisms, we discovered that a recently emerged, genetically distinct emm59 clone is responsible for the Canadian epidemic. Using near-real-time genome sequencing, we were able to show spread of the Canadian epidemic clone into the United States. The extensive genome data permitted us to identify patterns of geographic dissemination as well as links between emm59 subclonal lineages that cause infections. Mouse and nonhuman primate models of infection demonstrated that the emerged clone is unusually virulent. Transmission of epidemic emm59 strains may have occurred primarily by skin contact, as suggested by an experimental model of skin transmission. In addition, the emm59 strains had a significantly impaired ability to persist in human saliva and to colonize the oropharynx of mice, and seldom caused human pharyngitis. Our study contributes new information to the rapidly emerging field of molecular pathogenomics of bacterial epidemics and illustrates how full-genome data can be used to precisely illuminate the landscape of strain dissemination during a bacterial epidemic.
authors.affiliation: Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital System, Houston, Texas 77030, USA.
authors.forename: Nahuel
authors.initials: N
authors.lastname: Fittipaldi
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Beres
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.forename: Vivek
authors.initials: V
authors.lastname: Kapur
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Shea
authors.forename: M Ebru
authors.initials: ME
authors.lastname: Watkins
authors.forename: Concepcion C
authors.initials: CC
authors.lastname: Cantu
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Laucirica
authors.forename: Leslie
authors.initials: L
authors.lastname: Jenkins
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Flores
authors.forename: Marguerite
authors.initials: M
authors.lastname: Lovgren
authors.forename: Carmen
authors.initials: C
authors.lastname: Ardanuy
authors.forename: Josefina
authors.initials: J
authors.lastname: Liñares
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tyrrell
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000818:Animals; D002170:Canada / Q000453:epidemiology; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D058872:Epidemics; D019115:Fasciitis, Necrotizing / Q000382:microbiology / Q000473:pathology; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010612:Pharyngitis / Q000453:epidemiology / Q000382:microbiology; D010802:Phylogeny; D012463:Saliva / Q000382:microbiology; D017422:Sequence Analysis, DNA / Q000379:methods; D017192:Skin Diseases, Bacterial / Q000382:microbiology / Q000473:pathology; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014481:United States / Q000453:epidemiology; D014774:Virulence / Q000235:genetics
chemical_list: D004269:DNA, Bacterial