Phage steering of antibiotic-resistance evolution in the bacterial pathogen Pseudomonas aeruginosa

Abstract

Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads, but also select for phage resistance mechanisms that trade-off with antibiotic resistance - so called phage steering. Recent work has shown that phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity. We tested the robustness of this approach to three different antibiotics in vitro and one in vivo. We show that in vitro OMKO1 can reduce antibiotic resistance either in the absence or the presence of antibiotics. Our in vivo experiment showed that phage increased the survival times of wax moth larvae and increased bacterial sensitivity to erythromycin, both in the absence and presence of the antibiotic. We discuss the implications of our findings for future research on this promising therapeutic approach using OMKO1.