Quorum Sensing Promotes Phage Infection in Pseudomonas aeruginosa PAO1

Abstract

Quorum sensing (QS) is used to coordinate social behaviors, such as virulence and biofilm formation, across bacterial populations. However, the role of QS in regulating phage-bacterium interactions remains unclear. Preventing phage recognition and adsorption are the first steps of bacterial defense against phages; however, both phage recognition and adsorption are a prerequisite for the successful application of phage therapy. In the present study, we report that QS upregulated the expression of phage receptors, thus increasing phage adsorption and infection rates in Pseudomonas aeruginosa. In P. aeruginosa PAO1, we found that <i>las</i> QS, instead of <i>rhl</i> QS, upregulated the expression of <i>galU</i> for lipopolysaccharide synthesis. Lipopolysaccharides act as the receptor of the phage vB_Pae_QDWS. This <i>las</i> QS-mediated phage susceptibility is a dynamic process, depending on host cell density. Our data suggest that inhibiting QS may reduce the therapeutic efficacy of phages. <b>IMPORTANCE</b> Phage resistance is a major limitation of phage therapy, and understanding the mechanisms by which bacteria block phage infection is critical for the successful application of phage therapy. In the present study, we found that Pseudomonas aeruginosa PAO1 uses <i>las</i> QS to promote phage infection by upregulating the expression of <i>galU</i>, which is necessary for the synthesis of phage receptor lipopolysaccharides. In contrast to the results of previous reports, we showed that QS increases the efficacy of phage-mediated bacterial killing. Since QS upregulates the expression of virulence factors and promotes biofilm development, which are positively correlated with lipopolysaccharide production in P. aeruginosa, increased phage susceptibility is a novel QS-mediated trade-off. QS inhibition may increase the efficacy of antibiotic treatment, but it will reduce the effectiveness of phage therapy.