Bacterial Quorum Sensing Stabilizes Cooperation by Optimizing Growth Strategies

Abstract

Communication has been suggested as a mechanism to stabilize cooperation. In bacteria, chemical communication, termed quorum sensing (QS), has been hypothesized to fill this role, and extracellular public goods are often induced by QS at high cell densities. Here we show, with the bacterium Vibrio harveyi, that QS provides strong resistance against invasion of a QS defector strain by maximizing the cellular growth rate at low cell densities while achieving maximum productivity through protease upregulation at high cell densities. In contrast, QS mutants that act as defectors or unconditional cooperators maximize either the growth rate or the growth yield, respectively, and thus are less fit than the wild-type QS strain. Our findings provide experimental evidence that regulation mediated by microbial communication can optimize growth strategies and stabilize cooperative phenotypes by preventing defector invasion, even under well-mixed conditions. This effect is due to a combination of responsiveness to environmental conditions provided by QS, lowering of competitive costs when QS is not induced, and pleiotropic constraints imposed on defectors that do not perform QS. IMPORTANCECooperation is a fundamental problem for evolutionary biology to explain. Conditional participation through phenotypic plasticity driven by communication is a potential solution to this dilemma. Thus, among bacteria, QS has been proposed to be a proximate stabilizing mechanism for cooperative behaviors. Here, we empirically demonstrate that QS in V. harveyi prevents cheating and subsequent invasion by nonproducing defectors by maximizing the growth rate at low cell densities and the growth yield at high cell densities, whereas an unconditional cooperator is rapidly driven to extinction by defectors. Our findings provide experimental evidence that QS regulation prevents the invasion of cooperative populations by QS defectors even under unstructured conditions, and they strongly support the role of communication in bacteria as a mechanism that stabilizes cooperative traits. Cooperative behavior is a widespread phenomenon that pervades all levels of biological organization and has helped to catalyze all major transitions in the history of life (1). Extensive cooperation is also prevalent among microbes and plays fundamental roles in many bacterial processes, including biofilm formation, virulence, bioenergy, host-microbe interactions, and the formation of stable communities that maintain essential ecosystem functions (2-7). One class of microbial cooperative behaviors is the production of public goods (PG), i.e., products that provide benefits to both producers and nonproducers within a community. In the context of PG, individuals that contribute by producing the good are defined as cooperators, while nonproducers are defined as defectors. Importantly, defectors are not always inherently cheaters but are capable of cheating if they reap fitness advantages by exploiting social behaviors (8-10). Conditional participation through phenotyp...

Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios

“…However, bacterial populations can police themselves against cheaters via a number of mechanisms, including toxin production and metabolite exclusion (110,111). In V. harveyi, constitutive cooperators (ΔluxO mutant) and cheaters (ΔluxR mutant) have reduced growth yields or are outcompeted by the wild type under various conditions (112). Thus, a functional quorum sensing system can act as a controlling mechanism for the cooperative expression of global behaviors that are fine-tuned for growth performance.…”

Scale invariance during bacterial reductive division observed by an extensive microperfusion system

“…Such heterogeneity is not seen in the EMPS. While cell growth regulation pathways may also be influenced by such factors as mechanical pressure caused by cell elongation ( Volfson et al (2008) ; Boyer et al (2011) ; Si et al (2016) ; Chu et al (2018) ), quorum sensing ( Bruger and Waters (2016) ; Ha et al (2018) ), etc., our results indicate that the EMPS can indeed realize a uniform and stable culture condition while the same medium is kept supplied.…”

“…We then quickly switch the medium to a non-nutritious buffer, which is continuously supplied until the end of the observation (see Materials and Methods for more details). By doing so, we intend to remove various substances secreted by cells, such as autoinducers for quorum sensing and waste products, to reduce their effects on cell growth ( Carbonell et al (2002) ; Bruger and Waters (2016) ; Ha et al (2018 ); Maier and Pepper (2015) ). Throughout this experiment, the well is entirely recorded by phase contrast microscopy.…”

“…Combining with other theoretical methods, such as models considering the cellular age ( Grilli et al (2017) ) and renormalization group approaches for living cell tissues ( Rulands et al (2018) ), may be useful in this context. The influence of cell-to-cell interactions, e.g., quorum sensing ( Bruger and Waters (2016) ; Ha et al (2018) ), may also be important. We hope that our understanding of the population-level response against nutrient starvation will be further refined by future experimental and theoretical investigations.…”

Does quorum sensing interference affect the fitness of bacterial pathogens in the real world?

“…Hence, cheating by quorum sensingnonresponsive mutants in mixed populations with the quorum sensing-proficient wild type is an indication that resistance to quorum sensing inhibition will not spread (Mellbye and Schuster, 2011). Social cheating by quorum sensing-nonresponsive mutants has been documented in P. aeruginosa, both in laboratory cultures (Asfahl and Schuster, 2017) and Vibrio cholerae (Katzianer et al, 2015), whereas quorum sensing-deficient mutants of Bacillus thuringiensis were not effective cheats in moth larvae (Zhou et al, 2014), and quorum sensing provided resistance against invasion by a quorum sensingnonresponsive mutant in Vibrio harveyi in a medium containing casein as the sole carbon source (Bruger and Waters, 2016). Interestingly, clinical isolates of P. aeruginosa from chronic infections often have mutations in the AHL receptor gene lasR (Smith et al, 2006).…”