One if by land, two if by sea: signalling to the ranks with CSP and XIP

Abstract

In many streptococci, quorum sensing utilizes secreted, linear peptides that engage cognate receptors to coordinate gene expression among members of a local population. Streptococcus mutans employs the secreted peptides CSP and XIP to stimulate production of antimicrobial bacteriocins and to induce development of competence for genetic transformation. Recent progress in the field reveals that these pathways not only monitor the presence of signal emitters but also sense environmental factors. Both kinds of information are integrated by regulatory networks that then generate multiple outcomes, even among parallel cells growing in identical conditions. In this issue of Molecular Microbiology, Son and co-workers investigate how two medium types shape cellular responses to CSP and XIP pheromones in individuals across a population. Their findings characterize restrictive properties of media differing in peptidic fragment content and reveal unusual signalling properties that contribute to bimodal responses of gene expression.

Figure 1

Model of CSP and XIP quorum sensing in Streptococcus mutans. ComC (whose sequence is included at the bottom and color coded to illustrate processing sites) is secreted as a pre-peptide termed 21-CSP. CSP can be degraded by HtrA in a process affected by misfolded proteins. Productive processing by SepM generates the mature signal, 18-CSP, that binds to ComD leading to phosphorylation of ComE. ComE-P binds inverted repeat sites, indicated by a boxed “C”, enhancing transcription of bacteriocin genes. A positive feedback loop affecting ComE expression is proposed to include an additional regulatory component that establishes a bimodal expression pattern. ComS is secreted and processed by unknown components, but the mature form of the pheromone, XIP, comprises the last seven amino acids of ComS. XIP is imported via the oligopeptide permease (Opp), but transport is blocked by competing peptides present in complex media. Within the cell, an XIP-ComR complex binds to sites indicated by boxed “R” elements, activating transcription of comS and sigX. ComR and ComS are required to induce SigX, and SigX is required for transformation. In the report by Son et al. (Son et al., 2012), medium components are shown to modulate both CSP and XIP systems. In CDM, CSP does not induce competence, while XIP does so efficiently. In BHI, CSP stimulates competence, but, paradoxically, XIP signaling is blocked, yet comS remains required to stimulate sigX. For this reason it is proposed that ComS bypasses secretion and processing to interact with ComR directly.