Parallel quorum sensing signaling pathways in Vibrio cholerae

Abstract

Quorum sensing (QS) is a microbial signaling process for monitoring population density and complexity. Communication among bacterial cells via QS relies on the production, secretion, and detection of small molecules called autoinducers. Many bacteria have evolved their QS systems with different network architectures to incorporate information from multiple signals. In the human pathogen Vibrio cholerae, at least four parallel signaling pathways converge to control the activity of a single regulator to modulate its QS response. By integrating multiple signal inputs, it is believed that Vibrio species can survey intra-species, intra-genus, and inter-species populations and program their gene expression accordingly. Our recent studies suggest that this “many-to-one” circuitry is also important for maintaining the integrity of the input-output relationship of the system and minimizes premature commitment to QS due to signal perturbation. Here we discuss the implications of this specific parallel network setup for V. cholerae intercellular communication and how this system arrangement affects our approach to manipulate the QS response of this clinically-important pathogen.

Discovery of a Nitric Oxide Responsive Quorum Sensing Circuit in Vibrio cholerae

“…16 In contrast to other bacteria, in V. cholerae , low cell density triggers biofilm formation and secretion of virulence factors, and high cell density promotes biofilm dispersal and latency. When autoinducer concentrations are high, typically at high cell density, each receptor kinase binds its cognate autoinducer and acts as a phosphatase, drawing phosphate away from the common phosphotransfer protein LuxU.…”

Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios

“…The roles of LuxR and AphA as the master regulators of quorum sensing gene expression are conserved across the Vibrio genus, even when other factors within the signaling cascade differ (12,15,47). For example, V. harveyi has three cognate membrane-bound receptors ( Fig.…”

“…1), LuxN, LuxPQ, and CqsS, and each binds a specific autoinducer (autoinducer 1 [AI-1], AI-2, and cholera autoinducer 1 [CAI-1], respectively) (41). V. cholerae has four autoinducer receptors that feed into the same circuit to regulate HapR, one of which is unlike canonical Vibrio receptors in that it is not membrane bound (11)(12)(13). A new autoinducer-receptor pair was identified in V. cholerae; binding of the autoinducer 3,5-dimethylpyrazin-2-ol (DPO) is required for dimerization and function of the cytosolic transcription factor VqmA, which indirectly inhibits biofilm formation (51).…”

Ultrasensitivity and noise amplification in a model ofV. harveyiquorum sensing

“…(The human pathogen V. cholerae has a similar quorum sensing network, except there appear to be only two parallel pathways. Note, however, that a recent study suggests there could be up to four parallel pathways [30].) Each autoinducer moves freely between the intracellular and extracellular domains.…”