Bacteria use small molecules to assess the density and identity of other organisms in their surroundings and to make decisions about how to respond to their complex environment. This process, known as quorum sensing (QS), regulates diverse functions such as bioluminescence, biofilm formation, and virulence. In Vibrio harveyi three parallel QS circuits that synergistically regulate bioluminescence have been previously identified. These three systems involve the synthesis of three small molecules called autoinducers that bind to and regulate the phosphorylation of three cognate receptor histidine kinases. The three pathways then converge; all three kinases transfer phosphate to a common phosphorelay protein called LuxU. LuxU transfers phosphate to LuxO, a response regulator that controls expression of LuxR and, ultimately, the quorum sensing response. In this study, we show that another small molecule, nitric oxide (NO), participates in regulation of bioluminescence through the LuxU/LuxO/LuxR pathway. We show that V. harveyi display a NO concentration-dependent increase in light production that is regulated by expression of a NO-sensitive H-NOX gene. NO-bound H-NOX binds to and regulates the phosphorylation of a histidine kinase that, like the other QS kinases, transfers phosphate to LuxU. Thus, NO concentration is factored into the quorum sensing output of V. harveyi. This study reveals the discovery of a fourth quorum sensing pathway in Vibrio and suggests that bacteria use QS to integrate, not only the density of bacteria, but also other diverse information, such as the presence of eukaryotes, into decisions about gene expression. We anticipate this study to be a starting point for new investigations into the role of NO in bacteria and bacteria/host interactions. Furthermore, this study provides characterization of a new pathway that could be targeted for the development of novel antibiotics.

Nitric oxide is a quorum sensing molecule in Vibrio harveyi

243rd National Meeting (2012)

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