Evaluating Proteus mirabilis phage vB_PmiA_PM1 efficacy against catheter-associated urinary tract infections in artificial urine and laboratory media

Proteus mirabilis is a leading cause of catheter-associated urinary tract infections (CAUTI) because of its capability to develop extensive crystalline biofilms that obstruct catheters. Phages can effectively eradicate P. mirabilis biofilms in vitro; however, the clinical trial outcomes have been controversial. The current study aimed to investigate phage efficacy against P. mirabilis CAUTI in artificial urine medium (AUM) and laboratory media. A novel lytic P. mirabilis phage, vB_PmiA_PM1, was isolated and characterized. The phage had a narrow host range, capable of infecting only its main host strain, indicating high specificity. The phage also showed short latency, a large burst size, and physiochemical stability. The phage genome is linear double-stranded DNA (42,188 bp) with 59 open reading frames and closely resembles Salmonella phage vB_SpuP_Spp16. A putative depolymerase with a peptidoglycan hydrolase domain was identified within the phage tail protein, highlighting its role in the degradation of bacterial cells and the biofilm matrix. The bacteriolytic and biofilm-eradicating activities of this phage differed considerably between AUM and laboratory-rich media. Additionally, the growth dynamics of P. mirabilis in AUM exhibited less abundant growth as compared to that in trypticase soya broth. In addition, the formation of diverse struvite crystal morphotypes occurred as the pH increased. However, in the presence of vB_PmiA_PM1 phage, one morphotype of coffin-lid crystal was observed, which increased over time. Furthermore, phage activity on silicone Foley catheter sections demonstrated altered biofilm architecture and swarming migration in both media. These findings highlight the discrepancies between laboratory testing of phage and its clinical applications, which might fill the gaps in the future success of phage therapy against biofilm-associated CAUTI. Proteus mirabilis -mediated CAUTIs demonstrate characteristic crystalline biofilm on the catheter surface. Phage therapy in CAUTIs has shown promising efficacy in the laboratory. However, clinical trials have not reflected these findings. Evaluation of phage activity under conditions that closely mimic the intricate environment of a catheterized urinary tract could pave the way for successful phage application in CAUTIs.