Tripartite interactions between filamentous Pf4 bacteriophage,Pseudomonas aeruginosa, and bacterivorous nematodes

Abstract

AbstractThe opportunistic pathogenPseudomonas aeruginosaPAO1 is infected by the filamentous bacteriophage Pf4. Pf4 virions promote biofilm formation, protect bacteria from antibiotics, and modulate animal immune responses in ways that promote infection. Furthermore, strains cured of their Pf4 infection (ΔPf4) are less virulent in animal models of infection. Consistently, we find that strain ΔPf4 is less virulent in aCaenorhabditis elegansnematode infection model. However, our data indicate that PQS quorum sensing is activated and production of the pigment pyocyanin, a potent virulence factor, is enhanced in strain ΔPf4. The reduced virulence of ΔPf4 despite high levels of pyocyanin production may be explained by our finding thatC. elegansmutants unable to sense bacterial pigments through the aryl hydrocarbon receptor are more susceptible to ΔPf4 infection compared to wild-typeC. elegans. Collectively, our data support a model where suppression of quorum-regulated virulence factors by Pf4 allowsP. aeruginosato evade detection by innate host immune responses.Author SummaryPseudomonas aeruginosais an opportunistic bacterial pathogen that infects wounds, lungs, and medical hardware.P. aeruginosastrains are often themselves infected by a filamentous virus (phage) called Pf. At sites of infection, filamentous Pf virions are produced that promote bacterial colonization and virulence. Here, we report that strains ofP. aeruginosacured of their Pf infection are less virulent in aCaenorhabditis elegansnematode infection model. We also report that PQS quorum sensing and production of the virulence factor pyocyanin are enhanced inP. aeruginosastrains cured of their Pf infection. Compared to wild-typeC. elegans, nematodes unable to detect bacterial pigments via the aryl hydrocarbon receptor AhR were more susceptible to infection by Pf-freeP. aeruginosastrains that over-produce pyocyanin. Collectively, this study supports a model where Pf phage suppressP. aeruginosaPQS quorum sensing and reduce pyocyanin production, allowingP. aeruginosato evade AhR-mediated immune responses inC. elegans.