Biofilm formation is a key factor in
Vibrio cholerae
environmental survival and host colonization. Production of biofilm enables
V. cholerae
to survive and persist in aquatic environments and aids in the passage through the gastric acid barrier to allow access to the small intestine. The genes involved in biofilm formation are regulated by the transcriptional activators
vpsR
and
vpsT
, which are in turn transcriptionally regulated by a number of environmental signals. In this study, the role of the stringent response in biofilm formation was examined.
V. cholerae
mutants deficient in stringent response had a reduced ability to form biofilms, although they were not completely deficient in biofilm formation. There are three (p)ppGpp synthases in
V. cholerae
: RelA, SpoT, and RelV. All three synthases were necessary for
vpsR
transcription, with RelV showing the strongest effect. RelA was the only synthase that was necessary for
vpsT
expression. Stringent response regulation of
vpsR
and
vpsT
was shown to partially occur through
rpoS
. Biofilm formation in
V. cholerae
is controlled by a complex regulatory apparatus, with negative regulators of biofilm gene expression, such as quorum sensing, and positive regulators of biofilm genes, including stringent response, interacting to ensure that biofilm formation is coordinated with the environment.