Quorum-sensing, intra- and inter-species competition in the staphylococci

Abstract

In Gram-positive bacteria such as Staphylococcus aureus and the coagulase-negative staphylococci (CoNS), the accessory gene regulator (agr) is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm development. Signalling via agr depends on the interaction of an autoinducing peptide (AIP) with AgrC, a transmembrane sensor kinase that, once phosphorylated activates the response regulator AgrA. This in turn autoinduces AIP biosynthesis and drives target gene expression directly via AgrA or via the post-transcriptional regulator, RNAIII. In this review we describe the molecular mechanisms underlying the agr-mediated generation of, and response to, AIPs and the molecular basis of AIP-dependent activation and inhibition of AgrC. How the environment impacts on agr functionality is considered and the consequences of agr dysfunction for infection explored. We also discuss the concept of AIP-driven competitive interference between S. aureus and the CoNS and its anti-infective potential.

Ciprofloxacin enhances the biofilm formation of Staphylococcus aureus via an agrC-dependent mechanism

“…When AIP binds to AgrC above a threshold density, it modulates AgrC signaling and downstream gene expression ( Yarwood et al, 2004 ; Kavanaugh and Horswill, 2016 ). This triggers phosphorylation cascades in the Agr quorum sensing system, ultimately activating RNAIII to regulate S. aureus biofilm formation and dispersal ( Williams et al, 2023 ). As the key receptor, AgrC likely plays a critical regulatory role in biofilm development.…”

Physalin H, physalin B, and isophysalin B suppress the quorum-sensing function of Staphylococcus aureus by binding to AgrA

“…The virulence of S. aureus relies, in part, on the quorum sensing (QS) system, a mechanism of gene regulation in which bacteria coordinate the expression of certain genes in accordance with the concentration of small signal molecules ( Defoirdt et al, 2013 ). A master regulator is encoded by the virulence accessory gene regulator ( agr ) locus on its genome ( Patel and Rawat, 2023 ; Williams et al, 2023 ). The agr locus comprises divergent transcriptional units controlled by the P2 and P3 promoters.…”

Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing

“…In Gram-positive bacterial pathogens including the staphylococci, clostridia, enterococci and listeria, QS is mediated by the accessory gene regulator (agr) system [16,17] which reciprocally controls colonization and virulence gene expression. In S. aureus, the agr locus consists of two divergent transcriptional units (agrBCDA and RNAIII), controlled by the agrP2 and agrP3 promoters, respectively [17], (Figure 1). micro-organisms to synchronize gene expression within a population through cell-to-cell communication via the production and sensing of a self-generated, diffusible, signal molecule [15].…”

“…QS signal molecules are often called 'autoinducers' as they are responsible for driving their own biosynthesis [15]. In Gram-positive bacterial pathogens including the staphylococci, clostridia, enterococci and listeria, QS is mediated by the accessory gene regulator (agr) system [16,17] which reciprocally controls colonization and virulence gene expression. In S. aureus, the agr locus consists of two divergent transcriptional units (agrBCDA and RNAIII), controlled by the agrP2 and agrP3 promoters, respectively [17], (Figure 1).…”

“…This leads to activation of the agrP2 and agrP3 promoters driving the autoinduction circuitry to generate more AIPs so inducing the QS-dependent up-regulation of many exoproduct virulence genes and the down-regulation of cell wall colonization factors. (reproduced from [17]).…”