Investigating small RNA control of quorum sensing.

Princeton University, Princeton NJ

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Abstract

DESCRIPTION (provided by applicant): Quorum sensing is a process of chemical communication that bacteria use to assess fluctuations in the number of cells and species composition of the vicinal community. In response to changes in these parameters, bacteria switch between programs of gene expression underlying individual-cell and group- behavior-modes. Previously assumed to be an anomaly of a few marine bacteria, quorum-sensing-mediated communication is now understood to be the norm in the bacterial world. Investigating this process is vital to all of microbiology, most notably industrial and clinical microbiology, and this can be studied effectively using the model bioluminescent bacterium Vibrio harveyi, the bacterium in which quorum sensing was originally discovered. At the heart of the quorum-sensing cascade in V. harveyi are five non-coding small RNAs (sRNAs) that directly regulate expression of the master regulator, LuxR, which ultimately controls expression of the quorum-sensing genes. The goals of this proposal are to investigate how cells integrate and respond to particular combinations of extracellular cues by specifically examining the factors governing sRNA regulation and LuxR-directed quorum-sensing gene expression. In Specific Aim 1, I will identify and characterize the factors controlling the five sRNAs. Both genetic and biochemical approaches will be used to assess the individual contribution that each of the five Qrr sRNAs makes to quorum sensing. 1n Specific Aim 2, I will investigate differential regulation of quorum-sensing genes by LuxR in response to extracellular cues. In vivo expression assays, genetics, and biochemistry will be used to determine how LuxR differentially controls genes in response to particular extracellular cues. The timing and strength of LuxR- controlled gene expression will be examined to understand the quorum-sensing regulon. PUBLIC HEALTH RELEVANCE: Molecules that modulate quorum sensing have potential use as anti-microbial drugs aimed at bacteria that use quorum sensing to control virulence. Similarly, the biosynthetic enzymes involved in production of these small molecules are potential targets for novel anti-microbial drug design. Beyond the biotechnological and medical applications of this research, a continued study of quorum sensing promises to provide insight into novel mechanisms of intra- and inter-cellular signal transmission, intra- and inter-species communication, and the evolution of multi-cellularity.