ToxR regulates the production of lipoproteins and the expression of serum resistance in Vibrio cholerae.
The genes encoding three lipoproteins of Vibrio cholerae were identified by a combination of DNA sequence analysis and [3H]palmitate labeling of hybrid proteins encoded by TnphoA gene fusions. The expression of these three lipoproteins, TagA, AcfD, and TcpC, was controlled by ToxR, the cholera toxin transcriptional activator. The involvement of other bacterial lipoproteins in conferring resistance to the bactericidal effects of complement prompted us to examine this possibility in V. cholerae. Remarkably, mutations in toxR and tcp genes (including tcpC), involved in the biogenesis of the toxin coregulated pili, rendered V. cholerae about 10(4)-10(6) times more sensitive to the vibriocidal activity of antibody and complement. Since V. cholerae is a noninvasive organism and toxR and tcp mutants are highly defective in intestinal colonization in animals and humans, these results raise the possibility that resistance to a gut-associated, "complement-like" bactericidal activity may be a major virulence determinant of V. cholerae and other enterobacterial species.
Parsot
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Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Taxman
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Mekalanos
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D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000302:isolation & purification; D001426:Bacterial Proteins; D003165:Complement System Proteins / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006168:Guinea Pigs; D008074:Lipoproteins / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008074:Lipoproteins; D010169:Palmitic Acids; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae; C066719:toxR protein, bacteria; D019308:Palmitic Acid; D003165:Complement System Proteins