title: Relevance of spontaneous fabT mutations to a streptococcal toxic shock syndrome to non-streptococcal toxic shock syndrome transition in the novel-type Streptococcus pyogenes isolates that lost a salRK.
abstract: Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Mutations in covR/S or rgg, negative regulators, can reportedly modulate the severity of infection in this pathogen. Recently, we showed that the regions encoding the SalR-SalK, a two-component regulatory system, were deleted in some emm 1-type isolates (named as 'novel-type'). In this study, the two novel 'STSS' isolates 10-85stss and 11-171stss were more virulent than the two novel 'non-STSS' isolates 11O-2non and 11T-3non when examined using a mouse model of invasive infection. Genome-sequencing experiments using the three strains 10-85stss , 11-171stss , and 11O-2non detected only one single nucleotide polymorphism that causes a non-synonymous mutation in fabT encoding a transcriptional regulator in strain 11O-2non . Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non-STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O-2non , suggesting that the mutation in fabT, but not in covR/S or rgg, is involved in the differential virulence among the novel-type clinical isolates. This type of non-synonymous fabT mutation was also identified in 12 non-STSS isolates (including 11O-2non and 11T-3non ), and most of those 12 isolates showed impaired FabT function.
authors: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Ichiro
authors: I
authors: Tatsuno
authors: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Ryo
authors: R
authors: Okada
authors: Department of Microbiology and Medical Zoology, Aichi Prefectural Institute of Public Health, Nagoya, Aichi, Japan.
authors: Masakado
authors: M
authors: Matsumoto
authors: Department of Microbiology, Nagoya City University Hospital, Nagoya, Aichi, Japan.
authors: Nanako
authors: N
authors: Hata
authors: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Hideyuki
authors: H
authors: Matsui
authors: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Masanori
authors: M
authors: Isaka
authors: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Tadao
authors: T
authors: Hasegawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005809:Genes, Regulator; D016680:Genome, Bacterial; D006801:Humans; D008813:Mice, Inbred ICR; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012772:Shock, Septic / Q000382:microbiology / Q000473:pathology*; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology*; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D014774:Virulence
keywords: Streptococcus; Streptococcus pyogenes; fab; fabT; virulence