The Use of Bacteriophage Therapy To Treat Chronic Infections With Pseudomonas aeruginosa

Bacteriophage (phage) are bacterial viruses that are capable of killing bacteria. Due to the constant emergence of antibiotic-resistant bacteria the World Health Organisation (WHO) have stated that antibiotic resistances is a ‘global threat’ requiring alternatives. Phage therapy may represent one of the key alternatives. The opportunistic pathogen Pseudomonas aeruginosa is one of the most common causes of health care-associated infections, possessing the ability to rapidly develop resistance to multiple classes of antibiotics. P. aeruginosa can cause keratitis, urinary tract infections, infections in burns and wound patients and chronic lung infections. P. aeruginosa is the major pathogen associated with lung infections in cystic fibrosis (CF) patients, and once acquired chronic infection usually occurs, responsible for loss of respiratory function and eventual mortality. As a result, many studies have considered the efficacy of phage therapy. In this project, we will isolate phage to generate a phage library. We will then characterise the infective range and use next generation sequencing to generate a fully characterised phage library. An in vitro model of artificial sputum will be used to test phage both singly and within cocktails against P. aeruginosa bacterial biofilms. The evolution and training of phage in ASM will then be applied to bacterial isolates from patients. DNA sequencing will be used to study the accumulation of mutations after co-evolution between bacteria and phage. These phage combinations will then be tested in a mouse model of chronic respiratory infection to determine clearance from both the nasopharynx and the lungs. Phage may provide either a viable alternative to antibiotics or used in combination to increase efficacy and prolong the use of current antibiotics.

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