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Elucidation of the molecular mechanisms of Vibrio cholerae virulence and biofilm gene induction following host cell contact.

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Title Elucidation of the molecular mechanisms of Vibrio cholerae virulence and biofilm gene induction following host cell contact.
 
Creator Sengupta, Chirantana
 
Subject Infectious Diseases and Immunology
 
Description Vibrio cholerae, etiological agent of the disease cholera, is known to form biofilms for persistence in
the environment. Previously it has been shown that host cell contact can induce virulence in adhered
bacteria. The effect of host cell contact on biofilm formation was however not known. It is
demonstrated here that about 7 fold upregulation of the biofilm regulatory gene vpsT was observed
within 30 minutes of adherence of V. cholerae to the intestinal cell line INT 407 and a massive
induction of about 700 fold was observed in rabbit ileal loops. The upregulation was observed in both
the classical and El Tor biotype strains of serogroup O1 that is most frequently associated with
epidemic cholera. Though a number of regulators are known to regulate vpsT in vitro, vpsT
upregulation was primarily dependent on the virulence master regulator AphA in adhered bacteria
with VpsR playing a secondary role. Quorum sensing regulator LuxO, secondary molecules c-di-
GMP or negative regulator HNS were found to have no role in vpsT upregulation. Though AphA is a
virulence master regulator, the induction of biofilms upon host contact appears to be independent of
virulence induction and a distinct temporal speciation exists between the two events. It was observed
that during infection, biofilm genes are upregulated almost immediately after host cell contact and
microscopic observation indicated that biofilm formation is initiated within 30 mins after adherence of
V. cholerae to intestinal cells. Of possible clinical relevance was the observation that V. cholerae in
the INT 407 associated biofilms was significantly more resistant to antibiotics than unadhered
planktonic cells which could lead to a number of complications during treatment of cholera. The
induction of vpsT was observed in vivo in rabbit ileal loops as well and it was found to be independant
of the strain or biotype of V. cholerae. Overall this work is the first direct evidence that V. cholerae
forms antibiotic resistant biofilm within the host in an entirely host contact dependent manner.
 
Date 2016-11-30
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2580/1/CHIRANTANA_SENGUPTA_Thesis.pdf
Sengupta, Chirantana (2016) Elucidation of the molecular mechanisms of Vibrio cholerae virulence and biofilm gene induction following host cell contact. PhD thesis, C U.
 
Relation http://www.eprints.iicb.res.in/2580/