RsaM: a unique dominant regulator of AHL quorum sensing in bacteria

Abstract

Quorum sensing (QS) in proteobacteria is a mechanism to control gene expression orchestrated by the LuxI/LuxR protein family pair, which produces and responds to N-acyl homoserine lactone (AHL) diffusible signal molecules. QS is often regarded as a cell density response via the sensing of/response to the concentrations of AHLs, which are constantly basally produced by bacterial cells. The luxI/R systems, however, undergo supra-regulation in response to external stimuli and many regulators have been implicated in controlling QS in bacteria, although it remains unclear how most of these regulators and cues contribute to the QS response. One regulator, called RsaM, has been reported in a few proteobacterial species to have a stringent role in the control of AHL QS. RsaMs are small, in the range of 140-170 aa long, and are found in several genera, principally in Burkholderia and Acinetobacter. The gene encoding RsaM is always located as an independent transcriptional unit, situated adjacent to QS luxI and/or luxR loci. One of the most remarkable aspects of RsaM is its uniqueness; it does not fall into any of the known bacterial regulatory families and it possesses a distinct and novel fold that does not exhibit binding affinity for nucleic acids or AHLs. RsaM stands out as a distinctive regulator in bacteria, as it is likely to have an important ecological role, as well as unravelling a novel way of gene regulation in bacteria.

Keywords: AHL; LuxI/R; RsaM; bacteria; quorum sensing; regulation.

Fig. 1.

Taxonomic distribution and classification of RsaM in proteobacterial genomes. Genomes of proteobacteria from the IMG and NCBI databases were searched for the presence of rsaM genes (those that encode for proteins with domain PF16245). A tree of the RsaM representatives was made by aligning their protein sequences using clustal omega with standard settings [41], and then using FastTree with the alignment as input with standard settings [42]. The tree is annotated at genus level and the names of the best characterized RsaMs so far are indicated in the tree by an arrow in the external ring. Several hits belonging to bacterial genera that were detected as unique are grouped as ‘Others’. The tree is visualized and annotated using EMPress [43].

Fig. 2.

Diagrammatic representation of the mode of action of RsaM. Model of current knowledge on the RsaM regulator; see text for details. Dashed arrows represent a likely indirect regulatory mechanism.