title: Molecular characterization of an invasive phenotype of group A Streptococcus arising during human infection using whole genome sequencing of multiple isolates from the same patient.
abstract: Invasive group A streptococcal (GAS) strains often have genetic differences compared to GAS strains from nonsterile sites. Invasive, "hypervirulent" GAS strains can arise from a noninvasive progenitor following subcutaneous inoculation in mice, but such emergence has been rarely characterized in humans. We used whole genome analyses of multiple GAS isolates from the same patient to document the molecular basis for emergence of a GAS strain with an invasive phenotype during human infection. In contrast to previous theories, we found that elimination of production of the cysteine protease SpeB was not necessary for emergence of GAS with an invasive, "hypervirulent" phenotype.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Flores
authors.forename: Pranoti
authors.initials: P
authors.lastname: Sahasrabhojane
authors.forename: Miguel
authors.initials: M
authors.lastname: Saldaña
authors.forename: Jessica
authors.initials: J
authors.lastname: Galloway-Peña
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Shelburne
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002443:Ceftriaxone / Q000627:therapeutic use; D014644:Genetic Variation; D006801:Humans; D008297:Male; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D012883:Skin Ulcer / Q000188:drug therapy / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000145:classification* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone
keywords: bacterial pathogenesis; gene expression; group A Streptococcus; virulence; whole genome sequencing