Abstract

Multi-drug resistant (MDR) clinical strains of Pseudomonas aeruginosa are the most prevalent bacteria in the lungs of patients with cystic fibrosis (CF) and burn wounds and among the most common in immunocompromised hospital patients in Australia. There are currently no promising antibiotics in the pipeline being developed against these strains. Phage therapy, which uses viruses known as bacteriophages to infect and kill pathogenic bacteria, could be a possible alternative treatment. To this end, we isolated and characterised four novel phages against Australian clinical strains of P. aeruginosa isolated from patients with cystic fibrosis, from infected blood and joint aspirate in Southeast Queensland, Australia. Activated sludge was enriched for phages using the clinical strains, and four bacteriophages were isolated. The phages were able to cause lysis in a further three identified clinical isolates. Morphology showed that they were all tailed phages (of the order Caudovirales), two belonging to the family Myoviridae and the others assigned to the Podoviridae and Siphoviridae. Their genomes were sequenced to reveal a doubled stranded DNA topology with genome sizes ranging from 42 kb to 65 kb. In isolating and characterising these novel phages, we directed our efforts toward the development and use of these phages as candidates for phage therapy as an alternative strategy for the management or elimination of these pathogenic strains. Here we describe novel phage candidates for potential therapeutic treatment of MDR Australian clinical isolates of P. aeruginosa.

Highlights

  • Antimicrobial resistance (AMR) to conventional antibacterial compounds has soared, especially in treating hospitalacquired infections [1,2]

  • In this study we isolated a number of phages against Multi-drug resistant (MDR) clinical strains of P. aeruginosa isolated from Australian clinical environments and determined these phages had qualities that made them amenable for use as candidates for phage therapy against the targeted clinical isolates

  • Phages isolated against such clinical isolates are few and there are none so far isolated that are specific to the Australian clinical isolates of P. aeruginosa used in this study

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Summary

Introduction

Antimicrobial resistance (AMR) to conventional antibacterial compounds (e.g., βlactams, rifamycins, aminoglycosides etc.) has soared, especially in treating hospitalacquired (nosocomial) infections [1,2]. World Health Organisation listed five of these in the priority list for which new antibiotics are urgently needed. Without alternative treatments these AMR pathogens are projected to present an economic cost of 100 billion dollars and approximately 10 million deaths every year by 2050 [4,5,6]. P. aeruginosa has an array of adaptable features and mechanisms to survive, persist and resist a wide range of antibacterial therapies. These include, but are not limited to, exotoxin A, flagella, pili, proteases, phospholipases, lectins, siderophores, pyocyanin, 4.0/)

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