Bacterial quorum sensing: its role in virulence and possibilities for its control

Abstract

Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.

Figure 1.

Canonical bacterial quorum-sensing (QS) circuits. Autoinducing peptide (AIP) QS in Gram-positive bacteria by (A) two-component signaling, or (B) an AIP-binding transcription factor. Small molecule QS in Gram-negative bacteria by (C) a LuxI/LuxR-type system, or (D) two-component signaling.

Figure 2.

S. aureus Agr QS circuit. The autoinducing peptide (AIP) is synthesized as a precursor from agrD. The AIP transporter AgrB processes the precursor to the mature AIP and transports it out of the cell. AIPs are detected by a two-component signal transduction pathway. AgrC is the membrane-bound histidine kinase and AgrA is the response regulator. Phosphorylated AgrA activates the P2 and P3 promoters encoding the agr operon (called RNAII) and the RNAIII regulatory RNA, respectively. RNAIII posttranscriptionally activates virulence factor production and represses expression of rot, the repressor of toxins, leading to further derepression of virulence factors.

Figure 3.

B. cereus QS circuit. The pro-AIP PapR is secreted and is then processed to the mature heptapeptide AIP by the extracellular protease NprB. The mature AIP is transported back into the cell by Opp. Intracellular AIP binds to the transcription factor PlcR and activates it. The PlcR–AIP complex regulates virulence factor production and activates expression of papR.

Figure 4.

P. aeruginosa QS circuits. The three AI sythases, LasI, RhlI, and PqsABCDH, produce the AIs 3OC12HSL, C4HSL, and PQS, respectively. The AIs are detected by the cytoplasmic transcription factors LasR, RhlR, and PqsR, respectively. Each transcription factor regulates expression of its corresponding AI synthase as well as additional targets as indicated by the arrows.

Figure 5.

V. cholerae QS circuit. V. cholerae detects CAI-1 (produced by CqsA) and AI-2 (produced by LuxS) via two two-component histidine kinases, CqsS and LuxPQ, respectively. In the absence of AIs at LCD, the receptors function as kinases resulting in phosphorylation of LuxO, via LuxU, and activation of qrr gene expression. The Qrr sRNAs activate aphA and repress hapR expression. AphA represses hapR and activates tcpPH. TcpPH activates toxT expression and ToxT activates expression of the major virulence factors. At HCD, AIs bind the receptors switching them to phosphatases resulting in dephosphorylation of LuxO, cessation of qrr gene expression, and increased hapR expression. HapR represses aphA to shut down virulence factor production.