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Infection and Immunity, December 1998, p. 5854-5861, Vol. 66, No. 12
Department of Molecular
Biology,1
Infectious Disease
Division,2
Shriner's Burns
Institute,4 and
Department of
Surgery,3 Massachusetts General Hospital,
Boston, Massachusetts 02114, and
Department of
Genetics5 and
Department of Microbiology
and Molecular Genetics,6 Harvard Medical
School, Boston, Massachusetts 02115
Received 15 June 1998/Returned for modification 4 August
1998/Accepted 28 September 1998
The ToxRS system in Vibrio cholerae plays a central
role in the modulation of virulence gene expression in response to
environmental stimuli. An integration of multiple signalling inputs
mediated by ToxR, -S, and -T controls virulence gene expression leading to cholera toxin (CT) production. Recently, we identified a new virulence locus, varA (virulence associated regulator), in
classical V. cholerae O1 that positively controls
transcription of tcpA, the major subunit of the
toxin-coregulated pilus (TCP) and the production of CT, two key factors
in cholera pathogenesis. The varA locus is a homolog of
gacA (originally described for the soil organism
Pseudomonas fluorescens), which encodes a conserved global regulator belonging to the family of two-component signal transducing molecules. GacA homologs in a number of diverse
gram-negative pathogenic bacterial species have been implicated in
controlling the production of diverse virulence factors.
varA mutants showed reduced levels of tcpA
message and TcpA protein, lacked visible signs of autoagglutination (a
phenotype associated with functional TCP), produced decreased levels of
CT, and were attenuated in colonizing infant mice. Transcription of
varA appears to be independent of ToxR, and overexpression
of the regulators tcpPH and toxT from plasmids
in the varA mutant restored wild-type levels of CT
production and the ability to autoagglutinate. varA
represents an additional modulating factor in the coordinate expression
of virulence factors in V. cholerae.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Modulation of Expression of the ToxR Regulon in Vibrio
cholerae by a Member of the Two-Component Family of Response
Regulators

*
Corresponding author. Mailing address: Infectious
Disease Division, Massachusetts General Hospital, Boston, MA
02114. Phone: (617) 726-3811. Fax: (617) 726-7416. E-mail:
scalderwood{at}partners.org.
Present address: Department of Microbiology and Molecular Genetics,
Harvard Medical School, Boston, MA 02115.
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