title: Reduced virulence of the Vibrio cholerae fadD mutant is due to induction of the extracytoplasmic stress response.
abstract: Vibrio cholerae, an important human intestinal pathogen, is responsible for the diarrheal disease cholera. The pathogenesis of V. cholerae is a highly coordinated process that involves diverse regulatory factors. It has recently been demonstrated that disruption of the V. cholerae fadD gene, encoding a long-chain fatty acyl coenzyme A (acyl-CoA) ligase, drastically reduces expression of the major virulence genes and in vivo lethality of this important human pathogen. This effect was due to reduced membrane localization of the central virulence regulator TcpP. In this study, the reason for the impaired membrane localization of TcpP in the fadD mutant was investigated. We demonstrate that extracytoplasmic stress is induced in the V. cholerae ΔfadD strain. In response to the extracytoplasmic stress, the integral membrane protease RseP is activated and degrades the membrane-localized TcpP in the fadD mutant strain. Indeed, disruption of the rseP gene in a fadD mutant background restored membrane localization of TcpP and expression of the downstream virulence genes toxT, ctxA, and tcpA. Increased expression of the σ(E) regulon genes in ethanol-treated wild-type V. cholerae indicated that ethanol exposure could induce an extracytoplasmic stress response in V. cholerae. Ethanol treatment also led to activation of the RseP protease activity and resulted in degradation of membrane-localized TcpP and subsequent reduction in expression of the virulence genes. Taken together, these results suggest that extracytoplasmic stress response per se reduces virulence of V. cholerae by impairing membrane localization of TcpP.
authors.affiliation: Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.
authors.forename: Epshita
authors.initials: E
authors.lastname: Chatterjee
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Chowdhury
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D007082:Ileum / Q000382:microbiology; D009154:Mutation; D021381:Protein Transport; D011817:Rabbits; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C097244:TCPP protein, Vibrio cholerae; D014157:Transcription Factors
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