title: Mutation of the Thiol-Disulfide Oxidoreductase SdbA Activates the CiaRH Two-Component System, Leading to Bacteriocin Expression Shutdown in Streptococcus gordonii.
abstract: Streptococcus gordonii is a commensal inhabitant of the human oral cavity. To maintain its presence as a major component of oral biofilms, S. gordonii secretes inhibitory molecules such as hydrogen peroxide and bacteriocins to inhibit competitors. S. gordonii produces two nonmodified bacteriocins (i.e., Sth1 and Sth2) that are regulated by the Com two-component regulatory system, which also regulates genetic competence. Previously we found that the thiol-disulfide oxidoreductase SdbA was required for bacteriocin activity; however, the role of SdbA in Com signaling was not clear. Here we demonstrate that ΔsdbA mutants lacked bacteriocin activity because the bacteriocin gene sthA was strongly repressed and the peptides were not secreted. Addition of synthetic competence-stimulating peptide to the medium reversed the phenotype, indicating that the Com pathway was functional but was not activated in the ΔsdbA mutant. Repression of bacteriocin production was mediated by the CiaRH two-component system, which was strongly upregulated in the ΔsdbA mutant, and inactivation of CiaRH restored bacteriocin production. The CiaRH-induced protease DegP was also upregulated in the ΔsdbA mutant, although it was not required for inhibition of bacteriocin production. This establishes CiaRH as a regulator of Sth bacteriocin activity and links the CiaRH and Com systems in S. gordonii. It also suggests that either SdbA or one of its substrates is an important factor in regulating activation of the CiaRH system.
  
  
  OBJECTIVE
  Streptococcus gordonii is a noncariogenic colonizer of the human oral cavity. To be competitive in the oral biofilm, S. gordonii secretes antimicrobial peptides called bacteriocins, which inhibit closely related species. Our previous data showed that mutation of the disulfide oxidoreductase SdbA abolished bacteriocin production. In this study, we show that mutation of SdbA generates a signal that upregulates the CiaRH two-component system, which in turn downregulates a second two-component system, Com, which regulates bacteriocin expression. Our data show that these systems are also linked in S. gordonii, and the data reveal that the cell's ability to form disulfide bonds is sensed by the CiaRH system.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Davey
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada Department of Pediatrics, Faculty of Medicine, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada Department of Pediatrics, Faculty of Medicine, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada song.lee@dal.ca.
authors.forename: Song F
authors.initials: SF
authors.lastname: Lee
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001430:Bacteriocins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D054773:Streptococcus gordonii / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D008565:Membrane Proteins; C105449:SdbA protein, bacteria