title: Role of ToxS in the proteolytic cascade of virulence regulator ToxR in Vibrio cholerae.
abstract: Two of the primary virulence regulators of Vibrio cholerae, ToxR and TcpP, function together with cognate effector proteins. ToxR undergoes regulated intramembrane proteolysis (RIP) during late stationary phase in response to nutrient limitation at alkaline pH; however, the specific function of its cognate ToxS remains unresolved. In this work, we found that ToxR rapidly becomes undetectable in a ΔtoxS mutant when cultures are exposed to either starvation conditions or after alkaline pH shock individually. A ΔtoxS mutant enters into a dormant state associated with the proteolysis of ToxR at a faster rate than wild-type, closely resembling a ΔtoxR mutant. Using a mutant with a periplasmic substitution in ToxS, we found that the proteases DegS and DegP function additively with VesC and a novel protease, TapA, to degrade ToxR in the mutant. Overall, the results shown here reveal a role for ToxS in the stabilization of ToxR by protecting the virulence regulator from premature proteolysis.
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
authors: Salvador
authors: S
authors: Almagro-Moreno
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
authors: Michael Z
authors: MZ
authors: Root
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA.
authors: Ronald K
authors: RK
authors: Taylor
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019897:Periplasm / Q000378:metabolism; D033903:Periplasmic Proteins / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C066496:DegS protein, Bacteria; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D033903:Periplasmic Proteins; C097244:TCPP protein, Vibrio cholerae; D014157:Transcription Factors; D037521:Virulence Factors; C499324:toxR protein, Vibrio cholerae; C066828:ToxS protein, Vibrio cholerae; D010450:Endopeptidases; C061682:DegP protease; D012697:Serine Endopeptidases