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Published on: June 24, 2025
Development of a Phage Cocktail to Control Proteus mirabilis Catheter-associated Urinary Tract Infections
Luís D R Melo1, Patrícia Veiga1, Nuno Cerca1
1Laboratório de Investigação em Biofilmes Rosário Oliveira, Centre of Biological Engineering, University of Minho Braga Braga, Portugal.
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.
Insights
Two novel phages effectively combat Proteus mirabilis, a key cause of catheter-associated urinary tract infections (CAUTIs). These phages significantly reduce bacterial biofilm formation on catheters, offering a promising alternative to antibiotics.
Area of Science:
- Microbiology
- Bacteriology
- Virology
Background:
- Proteus mirabilis forms crystalline biofilms on catheters, causing difficult-to-treat catheter-associated urinary tract infections (CAUTIs).
- Biofilm tolerance to antibiotics makes CAUTIs a significant clinical challenge.
- Limited bacteriophage research exists for P. mirabilis control.
Purpose of the Study:
- To isolate and characterize novel virulent bacteriophages targeting P. mirabilis.
- To evaluate the efficacy of these phages in preventing P. mirabilis catheter colonization and biofilm formation.
Main Methods:
- Isolation and characterization of two virulent bacteriophages: podovirus vB_PmiP_5460 and myovirus vB_PmiM_5461.
- Genomic sequencing to confirm absence of lysogeny genes.
- Assessment of phage adherence to silicone surfaces.
- In vitro dynamic biofilm model simulating CAUTIs using phage-coated catheters.
Main Results:
- Two novel virulent phages, vB_PmiP_5460 and vB_PmiM_5461, were isolated.
- Phage vB_PmiP_5460 targets 16/26 P. mirabilis strains, while vB_PmiM_5461 targets all tested strains.
- Phages demonstrated adherence to silicone surfaces.
- Phage-coated catheters significantly reduced P. mirabilis biofilm formation for up to 168 hours.
Conclusions:
- The isolated phages show broad host range and lack lysogeny genes, indicating safety for therapeutic use.
- Phage-coated catheters effectively prevent P. mirabilis colonization and biofilm formation in a CAUTI model.
- These novel phages represent a promising strategy for preventing CAUTIs.
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