Quadruple Quorum-Sensing Inputs Control Group Behaviors in Vibrio cholerae
Quorum-Sensing (QS) is a microbial cell-to-cell communication process that allows
bacteria to function as a collective group and carry out robust, population-wide
behaviors that would be ineffective if performed alone. This inter-cellular signaling
process relies on cell density-dependent production and detection of chemical signals,
called autoinducers (AIs). Many pathogens, including ... read moreVibrio cholerae, the causative
agent of cholera, depend on QS to regulate important cellular processes essential for
adaptation and survival in the environment and within the host during infection. Since
its discovery, the V. cholerae QS system has served as a model to understand how
bacterial pathogens employ QS for temporal control of virulence factor production. Yet,
our understanding of the V. cholerae QS system remains incomplete. V. cholerae detects
two well-characterized AIs, CAI-1 and AI-2, with histidine kinase receptors, CqsS and
LuxPQ, respectively. At low cell density, these receptors function in parallel to
activate the key regulator LuxO, which is essential for virulence of this pathogen. At
high cell density, binding of AIs to their respective receptors leads to deactivation of
LuxO and repression of virulence factor production. However, mutants lacking CqsS and
LuxPQ maintain a normal LuxO activation level and remain virulent, suggesting that LuxO
is activated by additional signaling pathways. In this thesis, I define the V. cholerae
QS network architecture and examine how and why this pathogen maintains multiple QS
inputs. In the first study, I show that two novel histidine kinases, VpsS and CqsR,
function in parallel with CqsS and LuxPQ to regulate the V. cholerae QS circuit. In the
second study, I examine how QS receptor CqsR senses its signals. In the third study, I
investigate why V. cholerae maintains four parallel systems and test how V. cholerae
cells resist signal perturbations. Taken together, the results from this thesis suggest
that the V. cholerae QS circuit is composed of quadruple sensory inputs and this
integration is crucial for eliciting robust and coordinated QS
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Molecular Microbiology.
Advisors: Wai-Leung Ng, and Paula Watnick.
Committee: Andrew Camilli, Carol Kumamoto, and Ralph Isberg.
Keyword: Microbiology.read less