Abstract
Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials. Bacteriophages, or phages, are viruses that specifically infect bacteria and are a promising alternative to antimicrobials for CF P. aeruginosa infections. However, the narrow host range of P. aeruginosa-targeting phages and the rapid evolution of phage resistance could limit the clinical efficacy of phage therapy. A promising approach to overcome these issues is the strategic development of mixtures of phages (cocktails). The aim is to combine phages with broad host ranges and target multiple distinct bacterial receptors to prevent the evolution of phage resistance. However, further research is required to identify and characterize phage resistance mechanisms in CF-derived P. aeruginosa, which differ from their non-CF counterparts. In this review, we consider the mechanisms of P. aeruginosa phage resistance and how these could be overcome by an effective future phage therapy formulation.
Highlights
The increased rate of antimicrobial resistance in human and animal pathogens presents the prospect of a post-antibiotic era, prompting the World Health Organization (WHO) to compile a list of priority antimicrobial-resistant pathogens requiring the development of alternative antimicrobials [1]
The use of strains from non-cystic fibrosis (CF) origins in all but one of the studies of P. aeruginosa phage resistance [71] has neglected the contributions of the unique adaptions of CF clinical isolates of P. aeruginosa on phage therapy and resistance
Phage therapy is a promising alternative to antimicrobials in an increasingly post-antibiotic era
Summary
The increased rate of antimicrobial resistance in human and animal pathogens presents the prospect of a post-antibiotic era, prompting the World Health Organization (WHO) to compile a list of priority antimicrobial-resistant pathogens requiring the development of alternative antimicrobials [1]. The burden of antimicrobial-resistant infections will be greatest in individuals with chronic conditions, as they are disproportionately affected by bacterial infections [5]. Amongst these are people with cystic fibrosis (CF), who are predisposed to recurrent and persistent bacterial infections. Mutations result in dehydration of the air surface liquid on airway epithelial cells [6], leading to defective mucociliary clearance and the concentration of viscous mucus within the airways [7]. Prolonged and recurrent bacterial infections lead to respiratory failure, which is the most common cause of death in those with CF [12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
