Modulation of quorum sensing in Vibrio harveyi through multiple internal feedback loops

Abstract

Quorum sensing is the process of cell-to-cell communication in bacteria. Diverse bacteria use quorum sensing to control a variety of traits. Quorum sensing involves the production, release, and detection of small signaling molecules, called autoinducers. This allows a group of bacteria to coordinate gene expression and control group behaviors. The Gram-negative bacterium Vibrio harveyi posseses a quorum-sensing circuit that synthesizes and detects three autoinducers via three parallel sensory transduction pathways. In V. harveyi, quorum sensing controls the expression of genes essential for metabolically expensive functions, such as virulence and bioluminescence. Understanding how quorum sensing is regulated in V. harveyi will provide insight into how quorum-sensing-regulated behaivors are controlled, both in V. harveyi as well as in other quorum-sensing bacteria.

The aim of this work is to characterize how V. harveyi regulates the production and detection of the species specific autoinducer, called AI-1. We identify two internal quorum-sensing feedback loops that regulate the AI-1 synthase, LuxM, and the cognate receptor, LuxN. At low cell densities, a set of non-coding sRNAs bind to and mediate the degradation of the luxMN transcript. As cells transition from low to high cell density, the genes encoding the small RNAs are not expressed, resulting in increased translation of the luxMN mRNA. At high cell densities, the transcription factor LuxR indirectly represses LuxMN. Presumably, feedback causes a peak of LuxMN levels at the transition between low and high cell density, increasing the autoinducer concentration and the sensor levels, which results in a uniform transition across the population. We also characterize how these and other internal feedback loops alter the quorum-sensing response. We show that internal feedback loops control the range of AI-1 concentrations to which V. harveyi can respond, as well as set the dynamic window of the output response.