Progress in and promise of bacterial quorum sensing research

Abstract

This Review highlights how we can build upon the relatively new and rapidly developing field of research into bacterial quorum sensing (QS). We now have a depth of knowledge about how bacteria use QS signals to communicate with each other and to coordinate their activities. In recent years there have been extraordinary advances in our understanding of the genetics, genomics, biochemistry, and signal diversity of QS. We are beginning to understand the connections between QS and bacterial sociality. This foundation places us at the beginning of a new era in which researchers will be able to work towards new medicines to treat devastating infectious diseases, and use bacteria to understand the biology of sociality.

Box 1 image

Quorum-quenching membrane filtration (QQ-MBR) pilot plant system at sewage treatment facility in Seoul, South Korea. Professor Chung-Hak Lee of Seoul National University (center) has led a decade-long program to develop this technology

Box 2 Images

Left, Juvenile squid with infected light organ (boxed). The mantle has beed dissected to expose the light organ. Right, Fluorescence microscopy of light organ crypts colonized with a mix of YFP-labeled V. fischeri FQ-A001 and CFP labeled strain ES114. The three crypts in each lobe are outlined and labeled I, II and II. Images provided by T. Miyashiro Penn State University. Details of this type of experiment have been published previously.

Fig. 1. Canonical QS and the chemical diversity of signals

(A) Quorum sensing in Vibrio fischeri. LuxI produces 3O-C6-HSL (AHL, yellow spheres), which specifically interacts with the LuxR transcriptional regulator when it reaches concentrations in the nM range. This leads to expression of the luxICDABE operon and bioluminescence. (B) Examples of quorum sensing signals from Gram-negative and Gram-positive bacteria. (i) AHL, N-acyl homoserine lactone; (ii) 3-Hydroxy-AHL, N-(3-hydroxyacyl)homoserine lactone; (iii) 3-oxo-AHL, N-(3-oxoacyl)-L-homoserine lactone. R can be a fatty acyl group of 4–18 carbons with or without one unsaturated carbon-carbon bond, the terminal carbon can be branched and some R groups are aromatic acids (p-coumaric acid or cinnamic acid); (iv) The V. harveyi AI-2, autoinducer-2, furanosyl borate ester form; (v) PQS, Pseudomonas quinolone signal, 2-heptyl-3-hydroxy-4(1H)-quinolone; (vi) DSF, diffusible factor, methyl dodecenoic acid; (vii) PAME, hydroxyl-palmitic acid methyl ester; (viii) Autoinducing peptide 1 (AIP-1) from Staphylococcus aureus.

Fig. 2. Social cheating in QS populations

Bacterial cells act as cooperators (green) when secreting QS-dependent public goods (e.g. protease, red spheres) into the surrounding environment and this imposes a fitness cost on individual cells. Cheater cells (yellow) do not secrete these enzymes and pay no fitness costs. Cheats can benefit from the action of public goods and therefore gain a fitness advantage in mixed populations with cooperators. Orange halos depict a nutrient source liberated by a public good (e.g. protease) from which all cells (cooperators and cheats) can benefit.

Fig. 3. Factors that impact QS in natural environments

(A) LuxR orphans (solos) can detect and respond to signals produced by eukaryotic hosts, self, or other microbial species. (B) Top: Aggregates of two P. aeruginosa strains (green, strain PA14 and red, strain PAO1) in synthetic cystic fibrosis sputum . Bottom: Diagram of P. aeruginosa aggregates (3 clusters of red rods) spatially separated and socially isolated (yellow halos represent QS signals and QS-controlled exoproducts). (C) Top: Diagram of a high-density aggregate of QS positive cells (green) secreting a diffusible QS signal into the surrounding environment (orange halo). The signal can activate QS in a nearby cells (green) but not in more distant cells (yellow). Bottom: quorum quenching (orange stars), either by the action of enzymes or due to environmental conditions, degrades the QS signal and limits the ability of an aggregate to induce QS in nearby cells.