A Phage Cocktail To Control Surface Colonization by Proteus mirabilis in Catheter-Associated Urinary Tract Infections

Abstract

The rapid spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial strains and biofilm formation of bacteria have severely restricted the use of antibiotics and become a challenging issue in hospitals. Therefore, there is a necessity for alternative or complementary treatment measures, such as the use of virulent bacteriophages (phages), as effective therapeutic strategies. Proteus mirabilis is a biofilm-forming bacterium and one of the most common causes of catheter-associated urinary tract infections (CAUTIs). The rapid spread of multidrug-resistant P. mirabilis represents a severe threat to management of nosocomial infections. This study aimed to isolate a potent phage cocktail and assess its potential to control urinary tract infections caused by biofilm-forming P. mirabilis. Two lytic phages, Isf-Pm1 and Isf-Pm2, were isolated and characterized by proteome analysis, transmission electron microscopy, and whole-genome sequencing. The host range and effect of the phage cocktail to reduce the biofilm formation were assessed by a cell adhesion assay in Vero cells and a phantom bladder model. The samples treated with the phage cocktail showed a significant reduction (65) in the biofilm mass. Anti-quorum sensing and quantitative real-time PCR assays were also used to assess the amounts of transcription of genes involved in quorum sensing and biofilm formation. Furthermore, the phage-treated samples showed a downregulation of genes involved in the biofilm formation. In conclusion, these results highlight the efficacy of two isolated phages to control the biofilms produced by P. mirabilis CAUTIs. IMPORTANCE The rapid spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial strains and biofilm formation of bacteria have severely restricted the use of antibiotics and become a challenging issue in hospitals. Therefore, there is a necessity for alternative or complementary treatment measures, such as the use of virulent bacteriophages (phages), as effective therapeutic strategies.