Augmentation of the antimicrobial efficacy of antibiotics by filamentous phage

Area of Science:

• Microbiology
• Infectious Diseases
• Bacteriophage Therapy

Background:

• Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic and acquired antibiotic resistance.
• Antibiotic resistance poses a significant threat to public health, necessitating novel therapeutic strategies.
• Bacteriophages, viruses that infect bacteria, are being explored as alternatives or adjuncts to antibiotics.

Purpose of the Study:

• To investigate the effect of filamentous bacteriophages (Pf3 and Pf1) on the antibiotic sensitivity of Pseudomonas aeruginosa strains.
• To evaluate the potential of bacteriophage therapy in combination with antibiotics to treat P. aeruginosa infections in a murine model.

Main Methods:

• In vitro studies exposing P. aeruginosa strains O1 and K to phages Pf3 and Pf1, respectively, followed by antibiotic sensitivity testing.
• Infection of a P. aeruginosa K strain with a gentamicin resistance gene using phage Pf1 to assess re-sensitization.
• In vivo experiments using BALB/c mice with lethal P. aeruginosa K infections, treated with phage Pf1 and/or gentamicin.

Main Results:

• In vitro infection with phages Pf3 and Pf1 significantly increased antibiotic sensitivity in P. aeruginosa strains O1 and K.
• Phage Pf1 infection re-sensitized a gentamicin-resistant P. aeruginosa K strain to gentamicin.
• Concomitant administration of phage Pf1 and low-dose gentamicin rescued mice from lethal P. aeruginosa K infections, while neither treatment alone was effective.

Conclusions:

• Bacteriophage infection can modulate bacterial susceptibility to antibiotics.
• Combination therapy of bacteriophages and antibiotics shows promise for treating challenging P. aeruginosa infections.
• This approach may offer a new strategy to combat antibiotic-resistant bacterial pathogens.