Bacterial Quorum Sensing and Metabolic Incentives to Cooperate

Abstract

The opportunistic pathogen Pseudomonas aeruginosa uses a cell-cell communication system termed "quorum sensing" to control production of public goods, extracellular products that can be used by any community member. Not all individuals respond to quorum-sensing signals and synthesize public goods. Such social cheaters enjoy the benefits of the products secreted by cooperators. There are some P. aeruginosa cellular enzymes controlled by quorum sensing, and we show that quorum sensing-controlled expression of such private goods can put a metabolic constraint on social cheating and prevent a tragedy of the commons. Metabolic constraint of social cheating provides an explanation for private-goods regulation by a cooperative system and has general implications for population biology, infection control, and stabilization of quorum-sensing circuits in synthetic biology.Acyl-homoserine lactone (AHL) quorum sensing is common among Proteobacteria. This is a form of cell-cell communication that allows bacteria to monitor their population density and activate specific sets of genes when populations have reached a threshold density (1-3). Quorum sensing controls the production of a variety of public goods, functions shared by all individuals in the group. Experiments with P. aeruginosa support the view that quorum sensing controls cooperativity between P. aeruginosa cells (4-6). AHL signaling in P. aeruginosa is complex and involves multiple signals and receptors (7). A key system involves LasI, which generates the diffusible AHL signal N-3-oxododecanoylhomoserine lactone (C12-HSL) and LasR, a C12-HSL-responsive transcription activator (8). Together C12-HSL and LasR directly activate dozens of genes (9), with a heavy overrepresentation of genes coding for extracellular factors or production of extracellular factors, although there are some LasR-activated genes coding for cellular enzymes. Cellular enzymes are not shared among individuals so we call them private goods (10). By contrast, LasR-activated extracellular proteases are known as public goods (5). Growth of P. aeruginosa with casein or bovine serum albumin as the sole source of carbon and energy requires these proteases and encourages the emergence of LasR-mutant social cheaters (4, 5), which do not incur the cost of expressing quorum-controlled functions but benefit from the public goods produced by other members of the group. These cheaters have the potential to cause a "tragedy of the

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

“…Similar results were observed with a single lasR mutant during coculture under conditions requiring QS for growth (348). However, private goods controlled by QS (for example, nucleoside hydrolase, which allows for growth of P. aeruginosa on adenosine) are found to limit the emergence of cheaters when resources attainable only by private goods are at sufficient levels in the environment (349). Under these circumstances, cheaters arise but are kept at very low levels.…”

Non-social adaptation defers a tragedy of the commons in Pseudomonas aeruginosa quorum sensing

“…In microbes, other stabilizing mechanisms include positive assortment of cooperating individuals through, for example, colonial growth (Fletcher and Doebeli, 2009), the linkage of cooperative behaviors with other essential traits through pleiotropy (Foster et al, 2004) and metabolically prudent regulation of public goods such that their production is only initiated if the limiting nutrient is not also a building block of the good (Xavier et al, 2011;Mellbye and Schuster, 2014). It seems that pleiotropic control of extracellular proteolysis and subsequent intracellular metabolism via QS would be a reasonable strategy to curtail cheating, and a recent investigation using a similar in vitro evolution system has provided support for this notion (Dandekar et al, 2012). QS cheaters that do not contribute to proteolysis would be punished with reduced nutrient uptake and processing.…”

“…Intriguingly, however, this negative effect on group fitness was generally not observed during in vitro evolution experiments initiated solely with the wild-type strain, suggesting evolution of a mechanism that stabilized QS (Sandoz et al, 2007;Wilder et al, 2011;Dandekar et al, 2012).…”

“…A tragedy of the commons results when the magnitude of selfish exploitation by cheaters exceeds the capacity of a cooperative system, resulting in the collapse of the entire population. Indeed, several studies have demonstrated the emergence of QS cheaters that reap the benefits of cooperative secretions without metabolic investment both in vitro (Diggle et al, 2007;Sandoz et al, 2007;Wilder et al, 2011;Dandekar et al, 2012) and in vivo (Kohler et al, 2009;Rumbaugh et al, 2009). These QS cheaters are defined by a lossof-function mutation in the gene coding for the primary QS receptor LasR.…”

Programmed cell death in the marine cyanobacterium Trichodesmium mediates carbon and nitrogen export

“…One intriguing aspect of this PCD response is the potential role that quorum sensing (QS) may have in triggering its onset. QS is known to regulate the cell-cell communication and population response through the activation of different metabolic pathways including cell death (Dandekar et al, 2012), and QS has been recently documented to control phosphorus acquisition among Trichodesmium-epibiont consortia (Hewson et al, 2009b;Hmelo et al, 2012). Further investigation is needed to identify whether QS has any role in the PCD of Trichodesmium.…”