Development of a Phage Cocktail to Control Proteus mirabilis Catheter-associated Urinary Tract Infections

Abstract

Proteus mirabilis is an enterobacterium that causes catheter-associated urinary tract infections (CAUTIs) due to its ability to colonize and form crystalline biofilms on the catheters surface. CAUTIs are very difficult to treat, since biofilm structures are highly tolerant to antibiotics. Phages have been used widely to control a diversity of bacterial species, however, a limited number of phages for P. mirabilis have been isolated and studied. Here we report the isolation of two novel virulent phages, the podovirus vB_PmiP_5460 and the myovirus vB_PmiM_5461, which are able to target, respectively, 16 of the 26 and all the Proteus strains tested in this study. Both phages have been characterized thoroughly and sequencing data revealed no traces of genes associated with lysogeny. To further evaluate the phages’ ability to prevent catheter’s colonization by Proteus, the phages adherence to silicone surfaces was assessed. Further tests in phage-coated catheters using a dynamic biofilm model simulating CAUTIs, have shown a significant reduction of P. mirabilis biofilm formation up to 168 h of catheterization. These results highlight the potential usefulness of the two isolated phages for the prevention of surface colonization by this bacterium.

Hydrocinnamic acid produced byEnterobacter xiangfangensisimpairs AHL-based quorum sensing and biofilm formation inPseudomonas aeruginosa

“…Biolm inhibitory potential of E. xiangfangensis CFS was evaluated as dened. 20 Concisely, an overnight culture of P. aeruginosa was inoculated into LB broth with or without E. xiangfangensis CFS (5%). Biolms on spherical glass slides were formed as described above.…”

Indications and Limitations of Phage Therapy in Human Medicine: Personal Experience and Literature Review

“…It should also be mentioned that chronic urinary tract infections, despite the progress made in recent years, are still numerous [117] and responsible for the formation of dense biofilms on catheter surfaces that block urinary evacuation [118], as is the case with infections caused by Proteus mirabilis.…”

Prevention of encrustation and blockage of urinary catheters by Proteus mirabilis via pH-triggered release of bacteriophage

“…Although phage resistance has been reported, largely owing to changes in phage-receptor molecules, 28,29 this may be offset via the use of phage 'cocktails', where multiple strains of phage are directed against the target species. 21,[30][31][32] One of the major challenges in determining the effect of a therapeutic agent comes in achieving adequate local delivery to the site of infection. Often, controlled drug delivery systems rely on sustained passive delivery, although this often results in exposure of bacterial pathogens to sub lethal doses of chemical antibiotics, thus potentially contributing to the continued development of multidrug resistant species.…”

“…41 Previous studies investigating the ability of phage to reduce P. mirabilis biofilm biomass, either by entropic confinement of phage within a hydrogel, or simple administration of phage within an aqueous suspension has resulted in significant reduction P. mirabilis populations. 21,30,31,42 However, despite the successful outcomes of these investigations, the issue of formulating a working triggered release system has not been addressed.…”