title: Phase variation in tcpH modulates expression of the ToxR regulon in Vibrio cholerae.
abstract: We evaluated a spontaneous mutant of Vibrio cholerae, which was avirulent in an infant mouse and had reduced expression of cholera toxin and TcpA in response to environmental signals. The toxR, toxS and toxT genes in the mutant were normal, but transcription of toxT was absent. A plasmid expressing wild-type tcpP and tcpH complemented the mutant. The mutation resulted from a frameshift in a string of nine G residues within tcpH; similar slipped-strand mutations in tcpH arose at a frequency of 10(-4) during overnight growth and in the majority of colonies by the end of 5 days of growth in ToxR-inducing conditions. Transcription of tcpPH was regulated by temperature and pH independently of ToxR or ToxT. These results suggest that TcpH couples environmental signals (temperature and pH) to expression of the ToxR regulon, and provide a model for phase variation in the co-ordinate expression of cholera virulence factors.
authors.affiliation: Infectious Disease Division, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Carroll
authors.forename: K T
authors.initials: KT
authors.lastname: Tashima
authors.forename: M B
authors.initials: MB
authors.lastname: Rogers
authors.forename: V J
authors.initials: VJ
authors.lastname: DiRita
authors.forename: S B
authors.initials: SB
authors.lastname: Calderwood
mesh_terms: D000371:Agglutination; D000469:Alkaline Phosphatase / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002771:Cholera / Q000382:microbiology; D002772:Cholera Toxin / Q000096:biosynthesis / Q000235:genetics; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins / Q000235:genetics*; D036781:Fimbriae Proteins; D016368:Frameshift Mutation; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010641:Phenotype; D018085:Regulon; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014734:Vibrio cholerae / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; C097244:TCPP protein, Vibrio cholerae; C085807:TcpA protein, Vibrio cholerae; C099204:TcpH protein, Vibrio cholerae; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae; C066719:toxR protein, bacteria; C066828:ToxS protein, Vibrio cholerae; D036781:Fimbriae Proteins; C075626:tcpN protein, Vibrio cholerae; D002772:Cholera Toxin; D000469:Alkaline Phosphatase