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Accessing the In Vivo Efficiency of Clinically Isolated Phages against Uropathogenic and Invasive Biofilm-Forming
Swapnil Ganesh Sanmukh1,2, Joana Admella1, Laura Moya-Andérico1
1Bacterial Infections: Antimicrobial Therapies Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac, 15-21, 08028 Barcelona, Spain.
Abstract:
Escherichia coli is one of the most common members of the intestinal microbiota. Many of its strains are associated with various inflammatory infections, including urinary or gut infections, especially when displaying antibiotic resistance or in patients with suppressed immune systems. According to recent reports, the biofilm-forming potential of E. coli is a crucial factor for its increased resistance against antibiotics. To overcome the limitations of using antibiotics against resistant E. coli strains, the world is turning once more towards bacteriophage therapy, which is becoming a promising candidate amongst the current personalized approaches to target different bacterial infections. Although matured and persistent biofilms pose a serious challenge to phage therapy, they can still become an effective alternative to antibiotic treatment. Here, we assess the efficiency of clinically isolated phages in phage therapy against representative clinical uropathogenic and invasive biofilm-forming E. coli strains. Our results demonstrate that irrespective of host specificity, bacteriophages producing clear plaques with a high burst size, and exhibiting depolymerizing activity, are good candidates against biofilm-producing E. coli pathogens as verified from our in vitro and in vivo experiments using Galleria mellonella where survival was significantly increased for phage-therapy-treated larvae.
Insights
Bacteriophage therapy shows promise against antibiotic-resistant Escherichia coli biofilms. Specific bacteriophages with depolymerizing activity effectively reduced bacterial infections in lab and Galleria mellonella models, increasing survival rates.
Area of Science:
- Microbiology
- Infectious Diseases
- Biotechnology
Background:
- Escherichia coli is a common gut bacterium, with strains causing inflammatory infections, particularly in immunocompromised individuals or those with antibiotic resistance.
- Biofilm formation significantly enhances E. coli's resistance to antibiotics, posing a major challenge in clinical settings.
- Bacteriophage therapy is emerging as a personalized alternative to antibiotics for treating bacterial infections, including those caused by resistant strains.
Purpose of the Study:
- To evaluate the efficacy of clinically isolated bacteriophages against biofilm-forming, uropathogenic, and invasive Escherichia coli strains.
- To identify key bacteriophage characteristics that contribute to successful treatment of E. coli infections.
- To assess the potential of bacteriophage therapy as an alternative to antibiotics for combating resistant E. coli.
Main Methods:
- In vitro assessment of bacteriophage activity against clinical E. coli isolates.
- Evaluation of bacteriophage characteristics such as plaque formation, burst size, and depolymerizing activity.
- In vivo efficacy testing using Galleria mellonella infection models to measure survival rates.
Main Results:
- Clinically isolated bacteriophages demonstrated effectiveness against biofilm-producing E. coli.
- Bacteriophages with clear plaque formation, high burst size, and depolymerizing activity were identified as promising candidates.
- Phage therapy significantly increased the survival rate of Galleria mellonella larvae infected with E. coli.
Conclusions:
- Bacteriophage therapy is a viable alternative to antibiotics for treating E. coli infections, even those involving biofilms.
- Specific bacteriophage properties, including depolymerizing activity, are crucial for combating biofilm-forming E. coli.
- The study validates the use of bacteriophages against resistant E. coli through in vitro and in vivo experiments.
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