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.
Original language | English |
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Pages (from-to) | 4533-4546 |
Number of pages | 14 |
Journal | Environmental Microbiology |
Volume | 24 |
Issue number | 10 |
Early online date | 15 Jul 2022 |
DOIs | |
Publication status | Published - Oct 2022 |
Bibliographical note
Acknowledgments:We acknowledge funding from the BBSRC MIBTP (MBB/01116X/1) doctoral training centre to RL, HS and IA and the MRC doctoral training centre to RAJ (MR/J003964/1). There are no conflicts of interest to declare.
© 2022 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.
Keywords
- Anti-Bacterial Agents/pharmacology
- Bacteriophages/genetics
- Glycerophospholipids
- Glycolipids
- Humans
- Membrane Lipids
- Membrane Proteins
- Ornithine
- Phage Therapy/methods
- Phosphorus
- Pseudomonas Infections/therapy
- Pseudomonas aeruginosa