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Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems.

ABSTRACT: Pseudomonas aeruginosa coordinates the transcription of hundreds of genes, including many virulence genes, through three hierarchically arranged quorum-sensing (QS) systems, namely las, rhl and pqs. Each system consists of genes involved in autoinducer synthesis, lasI, rhlI and pqsABCDH, as well as cognate-regulatory genes, lasR, rhlR and pqsR. In this study, we analyzed the social behavior of signal-blind (?lasR, ?rhlR, ?pqsR) and signal-negative (?lasI, ?rhlI, ?pqsA) mutants from each QS system. As each system controls extracellular common goods but differs in the extent of regulatory control, we hypothesized that all signal-blind mutants can behave as cheaters that vary in their ability to invade a QS-proficient population. We found that lasR and pqsR, but not rhlR, mutants evolve from a wild-type ancestor in vitro under conditions that favor QS. Accordingly, defined lasR and pqsR mutants enriched in wild-type co-culture, whereas rhlR and all signal-negative mutants did not. Both lasR and pqsR mutants enriched with negative frequency dependence, suggesting social interactions with the wild type, although the pqsR mutant also grew well on its own. Taken together, the lasR mutant behaved as a typical cheater, as reported previously. However, the pqsR and rhlR mutants exhibited more complex behaviors, which can be sufficiently explained by positive and negative pleiotropic effects through differential regulation of pqs gene expression in the interconnected QS network. The evolutionary approach adopted here may account for the prevalence of naturally occurring QS mutants.

SUBMITTER: Wilder CN

PROVIDER: S-EPMC3146268 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems.

Wilder Cara N CN Diggle Stephen P SP Schuster Martin M

The ISME journal 20110303 8

Pseudomonas aeruginosa coordinates the transcription of hundreds of genes, including many virulence genes, through three hierarchically arranged quorum-sensing (QS) systems, namely las, rhl and pqs. Each system consists of genes involved in autoinducer synthesis, lasI, rhlI and pqsABCDH, as well as cognate-regulatory genes, lasR, rhlR and pqsR. In this study, we analyzed the social behavior of signal-blind (ΔlasR, ΔrhlR, ΔpqsR) and signal-negative (ΔlasI, ΔrhlI, ΔpqsA) mutants from each QS syste ...[more]

PMID: 21368905

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Project description:With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research. Possible innovative strategies include the inhibition of bacterial virulence. However, consideration must be given to the evolutionary and environmental consequences of such new interventions. Virulence and cooperative social behaviour of the bacterium Pseudomonas aeruginosa rely on the quorum-sensing (QS) controlled production of extracellular products (public goods). Hence QS is an attractive target for anti-virulence interventions. During colonization, non-cooperating (and hence less virulent) P. aeruginosa QS-mutants, benefiting from public goods provided by wild type isolates, naturally increase in frequency providing a relative protection from invasive infection. We hypothesized that inhibition of QS-mediated gene expression removes this growth advantage and selection of less virulent QS-mutants, and maintains the predominance of more virulent QS-wild type bacteria. We addressed this possibility in a placebo-controlled trial investigating the anti-QS properties of azithromycin, a macrolide antibiotic devoid of bactericidal activity on P. aeruginosa, but interfering with QS, in intubated patients colonized by P. aeruginosa. In the absence of azithromycin, non-cooperating (and hence less virulent) lasR (QS)-mutants increased in frequency over time. Azithromycin significantly reduced QS-gene expression measured directly in tracheal aspirates. Concomitantly the advantage of lasR-mutants was lost and virulent wild-type isolates predominated during azithromycin treatment. We confirmed these results in vitro with fitness and invasion experiments. Azithromycin reduced growth rate of the wild-type, but not of the lasR-mutant. Furthermore, the lasR-mutant efficiently invaded wild-type populations in the absence, but not in the presence of azithromycin. These in vivo and in vitro results demonstrate that anti-virulence interventions based on QS-blockade diminish natural selection towards reduced virulence and therefore may increase the prevalence of more virulent genotypes in the Hospital environment. More generally, the impact of intervention on the evolution of virulence of pathogenic bacteria should be assessed.

Project description:UnlabelledMany species of bacteria use a cell-cell communication system called quorum sensing (QS) to coordinate group activities. QS systems frequently regulate the production of exoproducts. Some of these products, such as proteases, are "public goods" that are shared among the population and vulnerable to cheating by nonproducing members of the population. Because the QS system of the opportunistic pathogen Pseudomonas aeruginosa regulates several public goods, it can serve as a model for studying cooperation. Bacteria also commonly regulate antimicrobial production through QS. In this study, we focused on the hypothesis that QS-regulated antimicrobials may be important for P. aeruginosa to protect against cheating by another bacterial species, Burkholderia multivorans. We assessed laboratory cocultures of P. aeruginosa and B. multivorans and investigated the importance of three P. aeruginosa QS-regulated antimicrobials, hydrogen cyanide, rhamnolipids, and phenazines, for competition. We found that P. aeruginosa dominates cocultures with B. multivorans and that the three antimicrobials together promote P. aeruginosa competitiveness, with hydrogen cyanide contributing the greatest effect. We show that these QS-regulated antimicrobials are also critical for P. aeruginosa to prevent B. multivorans from cheating under nutrient conditions where both species require a P. aeruginosa quorum-regulated protease for growth. Together our results highlight the importance of antimicrobials in protecting cooperating populations from exploitation by other species that can act as cheaters.ImportanceCooperative behaviors are threatened by social cheating, wherein individuals do not produce but nonetheless benefit from shared public goods. Bacteria have been shown to use several genetic mechanisms to restrain the emergence of cheaters from within the population, but public goods might also be used by other bacterial species in the vicinity. We demonstrate that a public good produced by Pseudomonas aeruginosa can be used by another species, Burkholderia multivorans, to obtain carbon and energy. We also show that P. aeruginosa antimicrobials that are coregulated with the public good prevent invasion by the cheating species. Our results demonstrate that cross-species cheating can occur and that coregulation of public goods with antimicrobials may stabilize cooperative behavior in mixed microbial communities.

Dataset Information

Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems.

Publications

Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems.

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