PQS Produced by the Pseudomonas aeruginosa Stress Response Repels Swarms Away from Bacteriophage and Antibiotics

Abstract

We investigate the effect of bacteriophage infection and antibiotic treatment on the coordination of swarming, a collective form of flagellum-and pilus-mediated motility in bacteria. We show that phage infection of the opportunistic bacterial pathogen Pseudomonas aeruginosa abolishes swarming motility in the infected subpopulation and induces the release of the Pseudomonas quinolone signaling molecule PQS, which repulses uninfected subpopulations from approaching the infected area. These mechanisms have the overall effect of limiting the infection to a subpopulation, which promotes the survival of the overall population. Antibiotic treatment of P. aeruginosa elicits the same response, abolishing swarming motility and repulsing approaching swarms away from the antibiotic-treated area through a PQS-dependent mechanism. Swarms are entirely repelled from the zone of antibiotic-treated P. aeruginosa, consistent with a form of antibiotic evasion, and are not repelled by antibiotics alone. PQS has multiple functions, including serving as a quorum-sensing molecule, activating an oxidative stress response, and regulating the release of virulence and host-modifying factors. We show that PQS serves additionally as a stress warning signal that causes the greater population to physically avoid cell stress. The stress response at the collective level observed here in P. aeruginosa is consistent with a mechanism that promotes the survival of bacterial populations. IMPORTANCE We uncover a phage-and antibiotic-induced stress response in the clinically important opportunistic pathogen Pseudomonas aeruginosa. Phage-infected P. aeruginosa subpopulations are isolated from uninfected subpopulations by the production of a stress-induced signal. Activation of the stress response by antibiotics causes P. aeruginosa to physically be repelled from the area containing antibiotics altogether, consistent with a mechanism of antibiotic evasion. The stress response observed here could increase P. aeruginosa resilience against antibiotic treatment and phage therapy in health care settings, as well as provide a simple evolutionary strategy to avoid areas containing stress.

Multicellular and unicellular responses of microbial biofilms to stress

“…This phenomenon was recently discovered for P. aeruginosa, where cells that were lysed by type VI secretion caused a rapid release of antibacterial compounds from neighboring kin cells (LeRoux et al 2015). Similarly, localized phage infection of P. aeruginosa can cause the affected cells to release the Pseudomonas quinolone signaling molecule (PQS), which repels other nearby cells from the infected area, constituting a response in the population that extends beyond the spatial location where the stress occurred (Bru et al 2019). To predation stresses that are very frequent, such as phage exposure, bacterial species have also adapted by producing particular biofilm matrix components that inhibit phage entry into the biofilms.…”

Genomic, Morphological and Functional Characterization of Virulent Bacteriophage IME-JL8 Targeting Citrobacter freundii

“…Bacteriophages lytic against other types of bacteria (e.g., Escherichia coli (Sadekuzzaman et al, 2017;Scanlan et al, 2017;Gilcrease and Casjens, 2018), Pseudomonas aeruginosa (Tsao et al, 2018;Bru et al, 2019) and Streptococcus (Leprohon et al, 2015;Lavelle et al, 2018;Szymczak et al, 2019) have been suggested to effectively disrupt mono-biofilms formed by their respective hosts. In this study, the morphological characterization and full genomic of a novel lytic bacteriophage, IME-JL8, were presented.…”

Spatiotemporal Distribution of Pseudomonas aeruginosa Alkyl Quinolones under Metabolic and Competitive Stress

“…Under conditions that promote the collective movement described as swarming, PQS has been shown to promote a protective response to some antibiotic classes (but not all) ( 23 , 24 ) and also to protect against phage infection ( 24 ). These findings are also related to earlier work reporting that PQS generally limits swarming expansion ( 18 ).…”