Bacterial Quorum Sensing and Metabolic Incentives to Cooperate

Cheat Control In quorum-sensing induction, a Pseudomonas aeruginosa population growing on a single carbon source, such as casein, will reach a density where the levels of signaling molecules they collectively secrete triggers the cells to synthesize and secrete proteases to digest the casein. However, it is metabolically costly to secrete proteases, and the system is prone to mutant “cheats.” These cheats do not respond to quorum sensing and do not go to the cost of synthesizing protease, but they do profit from the breakdown products that allow all the cells—cheats and cooperators alike—to grow. Dandekar et al. (p. 264) found that quorum signaling–insensitive P. aeruginosa cheats could not synthesize nucleotide hydrolase and were thus unable to grow if casein was replaced by adenosine. This allowed cooperators to outgrow the cheats, leading to a stable equilibrium between cheats and cooperators. This principle of regulation may be applicable to other bacterial quorum-sensing systems and might be exploited in the development of drugs that disrupt bacterial cooperation. Cooperating groups of bacteria resist infiltration by noncooperating cheats by co-regulating shared and individual products. 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.