title: Levels of the secreted Vibrio cholerae attachment factor GbpA are modulated by quorum-sensing-induced proteolysis.
abstract: Vibrio cholerae is the etiologic agent of cholera in humans. Intestinal colonization occurs in a stepwise fashion, initiating with attachment to the small intestinal epithelium. This attachment is followed by expression of the toxin-coregulated pilus, microcolony formation, and cholera toxin (CT) production. We have recently characterized a secreted attachment factor, GlcNAc binding protein A (GbpA), which functions in attachment to environmental chitin sources as well as to intestinal substrates. Studies have been initiated to define the regulatory network involved in GbpA induction. At low cell density, GbpA was detected in the culture supernatant of all wild-type (WT) strains examined. In contrast, at high cell density, GbpA was undetectable in strains that produce HapR, the central regulator of the cell density-dependent quorum-sensing system of V. cholerae. HapR represses the expression of genes encoding regulators involved in V. cholerae virulence and activates the expression of genes encoding the secreted proteases HapA and PrtV. We show here that GbpA is degraded by HapA and PrtV in a time-dependent fashion. Consistent with this, Delta hapA Delta prtV strains attach to chitin beads more efficiently than either the WT or a Delta hapA Delta prtV Delta gbpA strain. These results suggest a model in which GbpA levels fluctuate in concert with the bacterial production of proteases in response to quorum-sensing signals. This could provide a mechanism for GbpA-mediated attachment to, and detachment from, surfaces in response to environmental cues.
authors.affiliation: Dartmouth Medical School, Department of Microbiology and Immunology, Hanover, NH 03755, USA.
authors.forename: Brooke A
authors.initials: BA
authors.lastname: Jude
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Martinez
authors.forename: Karen
authors.initials: K
authors.lastname: Skorupski
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Taylor
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology*; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010447:Peptide Hydrolases; C513132:PrtV protein, Vibrio cholerae; D008666:Metalloendopeptidases; C039814:hemagglutinin-protease