title: Thermoregulation of capsule production by Streptococcus pyogenes.
abstract: The capsule of Streptococcus pyogenes serves as an adhesin as well as an anti-phagocytic factor by binding to CD44 on keratinocytes of the pharyngeal mucosa and the skin, the main entry sites of the pathogen. We discovered that S. pyogenes HSC5 and MGAS315 strains are further thermoregulated for capsule production at a post-transcriptional level in addition to the transcriptional regulation by the CovRS two-component regulatory system. When the transcription of the hasABC capsular biosynthetic locus was de-repressed through mutation of the covRS system, the two strains, which have been used for pathogenesis studies in the laboratory, exhibited markedly increased capsule production at sub-body temperature. Employing transposon mutagenesis, we found that CvfA, a previously identified membrane-associated endoribonuclease, is required for the thermoregulation of capsule synthesis. The mutation of the cvfA gene conferred increased capsule production regardless of temperature. However, the amount of the capsule transcript was not changed by the mutation, indicating that a post-transcriptional regulator mediates between CvfA and thermoregulated capsule production. When we tested naturally occurring invasive mucoid strains, a high percentage (11/53, 21%) of the strains exhibited thermoregulated capsule production. As expected, the mucoid phenotype of these strains at sub-body temperature was due to mutations within the chromosomal covRS genes. Capsule thermoregulation that exhibits high capsule production at lower temperatures that occur on the skin or mucosal surface potentially confers better capability of adhesion and invasion when S. pyogenes penetrates the epithelial surface.
authors.affiliation: Department of Microbiology, Southern Illinois University Carbondale, Carbondale, Illinois, United States of America.
authors.forename: Song Ok
authors.initials: SO
authors.lastname: Kang
authors.forename: Jordan O
authors.initials: JO
authors.lastname: Wright
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Tesorero
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Lee
authors.forename: Bernard
authors.initials: B
authors.lastname: Beall
authors.forename: Kyu Hong
authors.initials: KH
authors.lastname: Cho
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion / Q000502:physiology; D016667:Bacterial Capsules / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D004722:Endoribonucleases / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000502:physiology*; D013696:Temperature
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C534547:CovS protein, Streptococcus pyogenes; D000071677:Histidine Kinase; C575007:CvfA endoribonuclease, Streptococcus pyogenes; D004722:Endoribonucleases