Specificity and complexity in bacterial quorum-sensing systems

Abstract

Quorum sensing (QS) is a microbial cell-to-cell communication process that relies on the production and detection of chemical signals called autoinducers (AIs) to monitor cell density and species complexity in the population. QS allows bacteria to behave as a cohesive group and coordinate collective behaviors. While most QS receptors display high specificity to their AI ligands, others are quite promiscuous in signal detection. How do specific QS receptors respond to their cognate signals with high fidelity? Why do some receptors maintain low signal recognition specificity? In addition, many QS systems are composed of multiple intersecting signaling pathways: what are the benefits of preserving such a complex signaling network when a simple linear 'one-to-one' regulatory pathway seems sufficient to monitor cell density? Here, we will discuss different molecular mechanisms employed by various QS systems that ensure productive and specific QS responses. Moreover, the network architectures of some well-characterized QS circuits will be reviewed to understand how the wiring of different regulatory components achieves different biological goals.

Keywords: chemical signaling; gene expression; group behavior; intercellular communication; regulatory network.

Figure 1.

Basic QS circuit diagrams. (A) A Gram-negative one-component QS system. Autoinducer molecules are produced by the AI synthase, released into the extracellular environment, which are then diffused back into the cytoplasm where the QS receptor detects them, while also acting as a transcriptional regulator. (B) A Gram-negative two-component QS system. Autoinducer molecules are produced by the AI synthase, released into the extracellular environment, and are then detected by a transmembrane receptor. Detection of autoinducers triggers a phospho-relay that controls the downstream QS response. (C) A Gram-positive one-component QS system. Autoinducer peptides are produced by the AIP synthase and then released into the extracellular environment through a transporter, where they undergo proteolysis and are then transported back into the cytoplasm through a permease. In the cytoplasm, the modified AIP is detected by a QS receptor that also acts as a transcriptional regulator. (D) A Gram-positive two-component QS system. Autoinducer peptides are produced by the AIP synthase and released into the extracellular environment through a transporter where they undergo post-translational modifications and are then detected by a transmembrane receptor. Detection of autoinducer triggers a phospho-relay that controls the downstream QS response.

Figure 2.

Structures of bacterial autoinducers. (A) Acyl-homoserine lactones (AHSLs) that are produced by various Gram-negative bacteria. Shown is the AHL base structure, plus various R groups that differ among species. (B) Small peptide autoinducers (AIPs) called PapR produced by Bacillus genus. Predicted physiologically-relevant heptapeptides are indicated by additional residues in blue. (C) CAI-1 and its related autoinducers produced by Vibrio species. (D) The four AgrD variants produced by Staphylococcus aureus.

Figure 3.

Different QS network configurations. In a ‘One-to-One’ system, a single receptor controls the entire QS response. In a ‘Many-to-One’ parallel circuit, information contained in multiple autoinducers are integrated together to control the QS response. In a ‘Many-to-One’ hierarchical system, many QS receptors are connected in a signaling cascade in which the downstream receptor activity is controlled by the upstream receptors. Arrows and T-bar denote hypothetical activation and repression pattern, respectively.