PMID:9826365

Citation	Wong, SM, Carroll, PA, Rahme, LG, Ausubel, FM and Calderwood, SB (1998) Modulation of expression of the ToxR regulon in Vibrio cholerae by a member of the two-component family of response regulators. Infect. Immun. 66:5854-61
Abstract	The ToxRS system in Vibrio cholerae plays a central role in the modulation of virulence gene expression in response to environmental stimuli. An integration of multiple signalling inputs mediated by ToxR, -S, and -T controls virulence gene expression leading to cholera toxin (CT) production. Recently, we identified a new virulence locus, varA (virulence associated regulator), in classical V. cholerae O1 that positively controls transcription of tcpA, the major subunit of the toxin-coregulated pilus (TCP) and the production of CT, two key factors in cholera pathogenesis. The varA locus is a homolog of gacA (originally described for the soil organism Pseudomonas fluorescens), which encodes a conserved global regulator belonging to the family of two-component signal transducing molecules. GacA homologs in a number of diverse gram-negative pathogenic bacterial species have been implicated in controlling the production of diverse virulence factors. varA mutants showed reduced levels of tcpA message and TcpA protein, lacked visible signs of autoagglutination (a phenotype associated with functional TCP), produced decreased levels of CT, and were attenuated in colonizing infant mice. Transcription of varA appears to be independent of ToxR, and overexpression of the regulators tcpPH and toxT from plasmids in the varA mutant restored wild-type levels of CT production and the ability to autoagglutinate. varA represents an additional modulating factor in the coordinate expression of virulence factors in V. cholerae.
Links	PubMed PMC108741
Keywords	Animals; Bacterial Outer Membrane Proteins/biosynthesis; Bacterial Proteins/genetics; Cholera Toxin/biosynthesis; Cloning, Molecular; DNA-Binding Proteins/genetics; Down-Regulation; Fimbriae Proteins; Fimbriae, Bacterial/ultrastructure; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genes, Regulator; Mice; Molecular Sequence Data; Mutagenesis; Regulon; Sequence Homology, Amino Acid; Signal Transduction; Transcription Factors/genetics; Vibrio cholerae/genetics; Vibrio cholerae/pathogenicity; Virulence/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
VIBCH:Q9ZH73	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
VIBCL:Q9ZH73		GO:0009405: pathogenesis	ECO:0000315:		P		Table 2 shows the varA deficient mutant has reduced expression of cholera toxin when compared to wild type, and varA mutant reverted to wild type. Additionally, Table 4 shows that varA mutants have a lower competitive index in mice colonization.	complete CACAO 2177
VIBCL:Q9ZH73	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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