Class-Driven Synergy and Antagonism between a Pseudomonas Phage and Antibiotics

The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation gives physical refuge and a protected microenvironment for sessile cells, rendering cure by antibiotics a challenge. Bacteriophages have evolved to prey on these biofilms over millions of years, using hydrolases and depolymerases to penetrate biofilms and reach cellular targets. Here, we assessed how a newly discovered KMV-like phage (& phi;JB10) interacts with antibiotics to treat P. aeruginosa more effectively in both planktonic and biofilm forms. By testing representatives of four classes of antibiotics (cephalosporins, aminoglycosides, fluoroquinolones, and carbapenems), we demonstrated class-dependent interactions between & phi;JB10 and antibiotics in both biofilm clearance and P. aeruginosa killing. Despite identifying antagonism between some antibiotic classes and & phi;JB10 at early time points, all classes showed neutral to favorable interactions with the phage at later time points. In one notable example where the antibiotic alone had poor activity against both biofilm and high-density planktonic cells, we found that addition of & phi;JB10 demonstrated synergy and resulted in effective treatment of both. Further, & phi;JB10 seemed to act as an adjuvant to several antibiotics, reducing the concentration of antibiotics required to ablate the biofilm. This report shows that phages such as & phi;JB10 may be valuable additions to the armamentarium against difficult-to-treat biofilm-based infections. The ubiquitous bacterial pathogen Pseudomonas aeruginosa is responsible for severe infections in patients with burns, cystic fibrosis, and neutropenia. Biofilm formation gives physical refuge and a protected microenvironment for sessile cells, rendering cure by antibiotics a challenge.

Automated summary

The study investigated the interaction between a newly discovered phage (ΦJB10) and antibiotics in treating Pseudomonas aeruginosa infections. The results showed class-dependent interactions between ΦJB10 and antibiotics, with neutral to favorable interactions observed at later time points. The phage demonstrated synergy with antibiotics and acted as an adjuvant, reducing the concentration of antibiotics required to eliminate the biofilm. This highlights the potential value of phages like ΦJB10 in combating difficult-to-treat biofilm-based infections.