Many bacteria use quorum sensing (QS), a bacterial communication system based on the diffusion and perception of small signaling molecules, to synchronize their behavior in a cell-density dependent manner. QS regulates the expression of many genes associated with
virulence factor production and biofilm formation. This latter is known to be involved in
antibiotic and phage resistance mechanisms. Therefore, disrupting QS, a strategy known as quorum quenching (QQ), appears to be an interesting way to reduce bacterial virulence and increase
antibiotic and phage treatment efficiency. In this study, the ability of the QQ
enzyme SsoPox-W263I, a lactonase able to degrade
acyl-homoserine lactones, was investigated for quenching both virulence and biofilm formation in clinical isolates of Pseudomonas aeruginosa from
diabetic foot ulcers, as well as in the PA14 model strain. These strains were further evolved to resist to bacteriophage cocktails. Overall, 10
antibiotics or bacteriophage resistant strains were evaluated and SsoPox-W263I was shown to decrease
pyocyanin,
protease and
elastase production in all strains. Furthermore, a reduction of more than 70% of biofilm formation was achieved in six out of ten strains. This anti-virulence potential was confirmed in vivo using an amoeba
infection model, showing enhanced susceptibility toward amoeba of nine out of ten P. aeruginosa isolates upon QQ. This amoeba model was further used to demonstrate the ability of SsoPox-W263I to enhance the susceptibility of sensitive and phage resistant bacteria to bacteriophage and
antibiotic.