title: Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence.
abstract: Streptococcus pyogenes (group A Streptococcus; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the csrS/csrR (covS/covR) and/or rgg (ropB) genes, which are negative regulators of virulence. However, these mutations were found at somewhat low frequencies in emm1-genotyped isolates, the most prevalent STSS genotype. In this study, we sought to detect causal mutations of enhanced virulence in emm1 isolates lacking mutation(s) in the csrS/csrR and rgg genes. Three mutations associated with elevated virulence were found in the sic (a virulence gene) promoter, the csrR promoter, and the rocA gene (a csrR positive regulator). In vivo contribution of the sic promoter and rocA mutations to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the sic promoter mutation was significantly higher in STSS emm1 isolates than in non-invasive STSS isolates; the rocA gene mutation frequency was not significantly different among STSS and non-STSS isolates. STSS emm1 isolates possessed a high frequency mutation in the sic promoter. Thus, this mutation may play a role in the dynamics of virulence and STSS pathogenesis.
authors.affiliation: National Institute of Infectious Diseases, Department of Bacteriology I, Tokyo, 162-8640, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Ikebe
authors.affiliation: National Institute of Infectious Diseases, Department of Immunology, Tokyo, 162-8640, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Fukushima Institute of Public Health, Department of Microbiology, Fukushima, 960-8560, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Nihonmatsu
authors.affiliation: Kanagawa Prefectural Institute of Public Health, Division of Microbiology, Kanagawa, 253-0087, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ohya
authors.affiliation: Tokyo Metropolitan Institute of Public Health, Department of Microbiology, Tokyo, 169-0073, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Okuno
authors.affiliation: Toyama Institute of Health, Department of Bacteriology, Toyama, 939-0363, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Mitsui
authors.affiliation: Osaka Prefectural Institute of Public Health, Department of Infectious Diseases, Osaka, 537-0025, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kawahara
authors.affiliation: Yamaguchi Prefectural Institute of Public Health and Environment, Department of Public Health Sciences, Yamaguchi, 753-0821, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kameyama
authors.affiliation: Oita Prefectural Institute of Health and Environment, Laboratory of Microbiology, Oita, 870-1117, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Saitama Institute of Public Health, Laboratory of Clinical Microbiology, Saitama, 355-0133, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimada
authors.affiliation: National Institute of Infectious Diseases, Department of Immunology, Tokyo, 162-8640, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.affiliation: National Institute of Infectious Diseases, Department of Bacteriology I, Tokyo, 162-8640, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D012772:Shock, Septic / Q000235:genetics*; D013290:Streptococcal Infections / Q000235:genetics*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors