Membrane lipid renovation in Pseudomonas aeruginosa ‐ implications for phage therapy?

Abstract

Pseudomonas aeruginosa is an important Gram‐negative pathogen with intrinsic resistance to many clinically used antibiotics. It is particularly troublesome in nosocomial infections, immunocompromised patients, and individuals with cystic fibrosis. Antimicrobial resistance (AMR) is a huge threat to global health, with a predicted 10 million people dying from resistant infections by 2050. A promising therapy for combatting AMR infections is phage therapy. However, more research is required to investigate mechanisms that may influence the efficacy of phage therapy. An important overlooked aspect is the impact of membrane lipid remodelling on phage binding ability. P. aeruginosa undergoes changes in membrane lipids when it encounters phosphorus stress, an environmental perturbation that is likely to occur during infection. Lipid changes include the substitution of glycerophospholipids with surrogate glycolipids and the over‐production of ornithine‐containing aminolipids. Given that membrane lipids are known to influence the structure and function of membrane proteins, we propose that changes in the composition of membrane lipids during infection may alter phage binding and subsequent phage infection dynamics. Consideration of such effects needs to be urgently prioritised in order to develop the most effective phage therapy strategies for P. aeruginosa infections.

Advances in Development of Novel Therapeutic Strategies against Multi-Drug Resistant Pseudomonas aeruginosa

“…After prolonged incubation, phage resistance in P. aeruginosa was observed. Lipid remodeling during phage infection may alter binding and subsequent infection dynamics [83]. One case study described phage therapy for a complex bone and joint infection of XDR P. aeruginosa, in which phage therapy combined with ceftolozane/tazobactam and colistin resulted in rapid wound healing over 2 weeks [84].…”