The QscR Quorum-Sensing Regulon of Pseudomonas aeruginosa : an Orphan Claims Its Identity

Abstract

Quorum sensing is a process by which bacteria release and subsequently respond to signal molecules, as a mechanism for sensing population density (4). Acylated homoserine lactones (AHLs) are well-studied quorum-sensing signals among proteobacteria and are most commonly synthesized by enzymes of the LuxI family (3). AHLs are usually recognized by members of the LuxR family of transcription factors, often encoded adjacent to their corresponding LuxI-type AHL synthases. Proteobacterial genome sequencing has revealed the existence of many more LuxR homologues than were known or suspected to exist, frequently in significant excess over the number of recognized AHL synthases in the genome. Many of these regulatory genes are orphans, retaining key attributes of better-studied luxR homologues but not linked to or associated with an AHL synthase gene. Some of these orphans are substantially different in size from characterized LuxR homologues, with large truncations or additional sequences. Of those typically sized LuxR-type proteins with end-to-end similarity, many lack one or more conserved amino acid residues known to be critical to the function of most LuxR-type proteins (3). These imperfect LuxR homologues might function to recognize AHLs by an alternate mechanism, provide ligand-independent activity, act as dominant-negative inhibitors, or even detect alternate small molecules. In other cases, all or most of the critical residues are present. These more highly conserved LuxR-type orphans may respond to endogenously synthesized AHL(s), generated by an otherwise unassociated AHL synthase of the same microbe or possibly signals from different microbes. A study from Lequette et al., published in this issue of the Journal of Bacteriology, establishes the role of an intriguing orphan LuxR homologue called QscR (quorum-sensing control repressor) in a previously unrecognized regulatory pathway within the larger AHL quorum-sensing network of the opportunistic human pathogen Pseudomonas aeruginosa (12). This work provides important new insights into the activity of the orphan QscR protein within this complex control system and also illustrates an impressive application of DNA microarray technology to address specific hypotheses at a genomic scale.