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Phages against Pseudomonas aeruginosa in cystic fibrosis

 

Pseudomonas aeruginosa pulmonary infection is a leading cause of death among patients with cystic fibrosis. The spread of antibiotic-resistant strains of P. aeruginosa necessitates the search for new treatments. Bacteriophages are promising candidates.

The effectiveness of a phage cocktail against acute P. aeruginosa infection has previously been demonstrated in two animal models. The new study* used freshwater zebrafish, a popular and convenient model organism in biological research. While it might seem that an animal without lungs is an unlikely candidate for studying cystic fibrosis, the experiment used zebrafish with a knockout gene for the CFTR gene. This gene is virtually identical between humans and other animals, yet its defect causes cystic fibrosis in humans, while in zebrafish, it produces very similar symptoms.

The researchers infected zebrafish embryos with P. aeruginosa and, using fluorescent labels, observed the bacteria rapidly spreading throughout the embryo. The infection caused the death of at least 50% of the embryos within 20 hours of infection. As expected, embryos with cystic fibrosis symptoms were more susceptible to infection than control embryos.

Phage therapy for P. aeruginosa infection significantly reduced mortality among infected zebrafish embryos. Combination therapy with phage and the antibiotic ciprofloxacin proved particularly effective (more effective than either phage or antibiotic alone). This combination therapy reduces the dosage and duration of antibiotic treatment. The study notes that "phage therapy can reduce mortality, bacterial load, and the proinflammatory response induced by P. aeruginosa infection."

* Cafora M, Deflorian G, Forti F et al. Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model // Scientific Reports, 2019, 9, Article number: 1527. https://doi.org/10.1038/s41598-018-37636-x