vttRA and vttRB Encode ToxR family proteins that mediate bile-induced expression of type three secretion system genes in a non-O1/non-O139 Vibrio cholerae strain.
Strain AM-19226 is a pathogenic non-O1/non-O139 serogroup Vibrio cholerae strain that does not encode the toxin-coregulated pilus or cholera toxin but instead causes disease using a type three secretion system (T3SS). Two genes within the T3SS pathogenicity island, herein named vttR(A) (locus tag A33_1664) and vttR(B) (locus tag A33_1675), are predicted to encode proteins that show similarity to the transcriptional regulator ToxR, which is found in all strains of V. cholerae. Strains with a deletion of vttR(A) or vttR(B) showed attenuated colonization in vivo, indicating that the T3SS-encoded regulatory proteins play a role in virulence. lacZ transcriptional reporter fusions to intergenic regions upstream of genes encoding the T3SS structural components identified growth in the presence of bile as a condition that modulates gene expression. Under this condition, VttR(A) and VttR(B) were necessary for maximal gene expression. In contrast, growth in bile did not substantially alter the expression of a reporter fusion to the vopF gene, which encodes an effector protein. Increased vttR(B) reporter fusion activity was observed in a DeltavttR(B) strain background, suggesting that VttR(B) may regulate its own expression. The collective results are consistent with the hypothesis that T3SS-encoded regulatory proteins are essential for pathogenesis and control the expression of selected T3SS genes.
Alam
Ashfaqul
A
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Tam
Vincent
V
Hamilton
Elaine
E
Dziejman
Michelle
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001646:Bile / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D051379:Mice; D013312:Stress, Physiological; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D044163:Vibrio cholerae non-O1 / Q000187:drug effects* / Q000235:genetics; D014774:Virulence; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae; D001616:beta-Galactosidase
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