Molecular Effects of Fatty Acid uptake and Regulatory Gene Products on Survival, Virulence and Motility of the Enteric Pathogen
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Molecular Effects of Fatty Acid uptake and Regulatory Gene Products on Survival, Virulence and Motility of the Enteric Pathogen
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| Creator |
Chatterjee, Epshita
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| Subject |
Infectious Diseases and Immunology
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| Description |
Vibrio cholerae is the etiological agent of the diarrheal disease cholera. Expression of the major virulence factors of V. cholerae is controlled by the hierarchical expression of several regulatory proteins comprising the ToxR regulon which in turn is influenced by environmental parameters that promote optimal virulence induction in the pathogen. The objective of the present study was to elucidate the molecular basis for the hypo virulent phenotype of the fadD mutant. In this study we present evidence that a mutation in the fadD gene encoding a fatty acyl CoA ligase responsible for uptake and acylation of exogenous
fatty acids, has profound effects on the expression of virulence genes, motility and in vivo lethality of the human pathogen. The expression of major virulence genes ctxAB and tcpA was drastically repressed and a significant reduction in the expression of toxT, encoding a
cytoplasmic transcriptional activator of ctxAB and TCP operon was observed. Expression of toxT is activated by the synergistic effect of two membrane bound transcription factors ToxR and TcpP. Western blot analysis indicated that although ToxR production and membrane localisation remains unaltered in the V. cholerae fadD mutant, membrane localisation of TcpP is severely impaired, suggesting a direct correlation between reduced toxT expression
and defective membrane localisation of TcpP. In response to the extracytoplasmic stress, the integral membrane protease RseP is known to be activated and degrades TcpP. 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 in addition to increased expression of σE regulon genes. Increased expression of the σE 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.
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| Date |
2013
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1990/1/Epshita_Chatterjee%2C_Ph.D._Thesis.pdf
Chatterjee, Epshita (2013) Molecular Effects of Fatty Acid uptake and Regulatory Gene Products on Survival, Virulence and Motility of the Enteric Pathogen. PhD thesis, Calcutta University. |
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| Relation |
http://www.eprints.iicb.res.in/1990/
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