Bacterial quorum sensing enables bacteria to cooperate in a densitydependent manner via the group-wide secretion and detection of specific autoinducer molecules. Many bacterial species show high intraspecific diversity of autoinducer-receptor alleles, called pherotypes. The autoinducer produced by one pherotype activates its coencoded receptor, but not the receptor of another pherotype. It is unclear what selection forces drive the maintenance of pherotype diversity. Here, we use the ComQXPA system of Bacillus subtilis as a model system, to show that pherotype diversity can be maintained by facultative cheating-a minority pherotype exploits the majority, but resumes cooperation when its frequency increases. We find that the maintenance of multiple pherotypes by facultative cheating can persist under kin-selection conditions that select against "obligate cheaters" quorum-sensing response null mutants. Our results therefore support a role for facultative cheating and kin selection in the evolution of quorum-sensing diversity.social evolution | sociomicrobiology | Bacillus subtilis | bacteria | quorum sensing I n many bacteria, a cell-cell signaling mechanism, known as quorum sensing, coordinates the response of a bacterial community in a density-dependent manner. Quorum-sensing bacteria secrete a signal molecule known as an autoinducer and express a specific receptor that binds to it with high affinity, resulting in the activation of a specific cellular response (1). Quorum sensing often regulates the secretion of public goods or other cooperative traits that benefit the community, at a cost to the individual responding cell (2).The regulation of cooperation by a secreted autoinducer allows for the evolution of cheater genotypes that do not produce the autoinducer or do not respond to it (3, 4). Mutants of the latter type were shown to act as cheaters in a variety of different species (3-7). The elimination of these cheater mutants could occur by kin selection, where cooperation is preferentially directed toward other cooperators (3,(7)(8)(9).In contrast to the rarity of quorum-sensing response null alleles in wild populations, many species display a high degree of intraspecific genetic variation in functional quorum-sensing alleles, called pherotypes (Fig. 1A). Each allele codes for both receptor and autoinducer genes, where an autoinducer coded by one pherotype will activate its coencoded receptor, but not the receptors encoded by other pherotypes (10-14). Pherotypes differ in their receptor-autoinducer specificity but not in the pathways regulated by the receptor. In addition, many pherotypes show patterns of intraspecific horizontal gene transfer (10, 12) and coexist in the same environment (15, 16).The mechanisms that lead to the diversification of pherotypes, to the maintenance of their diversity, and to their rapid horizontal gene transfer are not well understood. We have previously proposed, by analyzing a theoretical model, that if quorum sensing regulates cooperation, novel pherotypes can arise adaptivel...

Quorum sensing is a process of chemical communication that bacteria use to monitor cell density and coordinate cooperative behaviors. Quorum sensing relies on extracellular signal molecules and cognate receptor pairs. While a single quorum-sensing system is sufficient to probe cell density, bacteria frequently use multiple quorum-sensing systems to regulate the same cooperative behaviors. The potential benefits of these redundant network structures are not clear. Here, we combine modeling and experimental analyses of the Bacillus subtilis and Vibrio harveyi quorum-sensing networks to show that accumulation of multiple quorum-sensing systems may be driven by a facultative cheating mechanism. We demonstrate that a strain that has acquired an additional quorum-sensing system can exploit its ancestor that possesses one fewer system, but nonetheless, resume full cooperation with its kin when it is fixed in the population. We identify the molecular network design criteria required for this advantage. Our results suggest that increased complexity in bacterial social signaling circuits can evolve without providing an adaptive advantage in a clonal population.

In bacterial communities, cells often communicate by the release and detection of small diffusible molecules, a process termed quorum-sensing. Signal molecules are thought to broadly diffuse in space; however, they often regulate traits such as conjugative transfer that strictly depend on the local community composition. This raises the question how nearby cells within the community can be detected. Here, we compare the range of communication of different quorum-sensing systems. While some systems support long-range communication, we show that others support a form of highly localized communication. In these systems, signal molecules propagate no more than a few microns away from signaling cells, due to the irreversible uptake of the signal molecules from the environment. This enables cells to accurately detect micron scale changes in the community composition. Several mobile genetic elements, including conjugative elements and phages, employ short-range communication to assess the fraction of susceptible host cells in their vicinity and adaptively trigger horizontal gene transfer in response. Our results underscore the complex spatial biology of bacteria, which can communicate and interact at widely different spatial scales.

Bacterial cell-cell signaling, or quorum sensing, is characterized by the secretion and group-wide detection of small diffusible signal molecules called autoinducers. This mechanism allows cells to coordinate their behavior in a density-dependent manner. A quorum-sensing cell may directly respond to the autoinducers it produces in a cell-autonomous and quorum-independent manner, but the strength of such self-sensing effect and its impact on bacterial physiology are unclear. Here, we explored the existence and impact of self-sensing in the Bacillus subtilis ComQXP and Rap-Phr quorum-sensing systems. By comparing the quorum-sensing response of autoinducer-secreting and non-secreting cells in co-culture, we found that secreting cells consistently showed a stronger response than non-secreting cells. Combining genetic and quantitative analyses, we demonstrated this effect to be a direct result of self-sensing and ruled out an indirect regulatory effect of the autoinducer production genes on response sensitivity. In addition, self-sensing in the ComQXP system affected persistence to antibiotic treatment. Together, these findings indicate the existence of self-sensing in the two most common designs of quorum-sensing systems of Gram-positive bacteria.

No abstract