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A Phage Cocktail To Control Surface Colonization by Proteus mirabilis in Catheter-Associated Urinary Tract Infections
Arezoo Mirzaei1, Jeroen Wagemans2, Bahram Nasr Esfahani1
1Department of Bacteriology and Virology, School of Medicine, Isfahan University of Medical Sciencesgrid.411036.1, Isfahan, Iran.
Abstract:
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.
Insights
A potent phage cocktail effectively reduced biofilm formation in Proteus mirabilis, a common cause of catheter-associated urinary tract infections (CAUTIs). This offers a promising alternative to antibiotics for combating drug-resistant bacterial infections.
Area of Science:
- Microbiology
- Bacteriology
- Infectious Diseases
Background:
- Proteus mirabilis is a significant cause of catheter-associated urinary tract infections (CAUTIs) due to its biofilm-forming capabilities.
- The rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. mirabilis strains poses a severe threat to healthcare settings.
- Antibiotic resistance and bacterial biofilm formation necessitate the development of alternative therapeutic strategies.
Purpose of the Study:
- To isolate and characterize lytic bacteriophages effective against biofilm-forming P. mirabilis.
- To evaluate the efficacy of a phage cocktail in controlling P. mirabilis-associated CAUTIs.
- To investigate the impact of phage treatment on bacterial quorum sensing and biofilm gene expression.
Main Methods:
- Isolation and characterization of two lytic phages (Isf-Pm1 and Isf-Pm2) using proteome analysis, transmission electron microscopy, and whole-genome sequencing.
- Assessment of phage cocktail efficacy using cell adhesion assays in Vero cells and a phantom bladder model.
- Analysis of gene transcription related to quorum sensing and biofilm formation via anti-quorum sensing assays and quantitative real-time PCR.
Main Results:
- The phage cocktail demonstrated a significant 65% reduction in P. mirabilis biofilm mass.
- Phage treatment led to the downregulation of key genes involved in biofilm formation.
- The study successfully identified potent lytic phages against P. mirabilis.
Conclusions:
- The isolated phage cocktail is effective in controlling biofilms produced by P. mirabilis, offering a potential therapeutic strategy for CAUTIs.
- Bacteriophage therapy presents a viable alternative or complementary approach to antibiotics for managing nosocomial infections caused by resistant bacteria.
- This research highlights the therapeutic potential of phage cocktails against challenging bacterial pathogens.
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