title: Host cell contact induces expression of virulence factors and VieA, a cyclic di-GMP phosphodiesterase, in Vibrio cholerae.
abstract: Vibrio cholerae, a noninvasive bacterium, colonizes the intestinal epithelium and secretes cholera toxin (CT), a potent enterotoxin that causes the severe fluid loss characteristic of the disease cholera. In this study, we demonstrate that adherence of V. cholerae to the intestinal epithelial cell line INT 407 strongly induces the expression of the major virulence genes ctxAB and tcpA and the virulence regulatory gene toxT. No induction of toxR and tcpP, which encode transcriptional activators of toxT, was observed in adhered bacteria, and the adherence-dependent upregulation of toxT expression was independent of ToxR and TcpP. A sharp increase in the expression of the vieA gene, which encodes a cyclic di-GMP (c-di-GMP) phosphodiesterase, was observed in INT 407-adhered V. cholerae immediately after infection. Induction of toxT, ctxAB, and tcpA in INT 407-adhered vieA mutant strain O395 ΔvieA was consistently lower than in the parent strain, although no effect was observed in unadhered bacteria, suggesting that VieA has a role in the upregulation of toxT expression specifically in host cell-adhered V. cholerae. Furthermore, though VieA has both a DNA binding helix-turn-helix domain and an EAL domain conferring c-di-GMP phosphodiesterase activity, the c-di-GMP phosphodiesterase activity of VieA is necessary and sufficient for the upregulation of toxT expression.
authors: Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.
authors: Amit K
authors: AK
authors: Dey
authors: Abha
authors: A
authors: Bhagat
authors: Rukhsana
authors: R
authors: Chowdhury
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002771:Cholera / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D054884:Host-Pathogen Interactions; D006801:Humans; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; C112165:VieA protein, Vibrio cholerae; D037521:Virulence Factors; C075626:tcpN protein, Vibrio cholerae; D015106:3',5'-Cyclic-GMP Phosphodiesterases