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Membrane lipid renovation in Pseudomonas aeruginosa - implications for phage therapy?
Environmental Microbiology ( IF 4.3 ) Pub Date : 2022-07-15 , DOI: 10.1111/1462-2920.16136
Rhiannon Lyon 1, 2 , Rebekah A Jones 2, 3 , Holly Shropshire 1, 2 , Isabel Aberdeen 1, 2 , David J Scanlan 2 , Andrew Millard 4 , Yin Chen 2
Affiliation  

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.

中文翻译:

铜绿假单胞菌的膜脂修复——对噬菌体治疗的影响?

铜绿假单胞菌是一种重要的革兰氏阴性病原体,对许多临床使用的抗生素具有固有耐药性。它在院内感染、免疫功能低下的患者和患有囊性纤维化的个体中尤其麻烦。抗菌素耐药性 (AMR) 是对全球健康的巨大威胁,预计到 2050 年将有 1000 万人死于耐药性感染。噬菌体疗法是​​一种很有前途的对抗 AMR 感染的疗法。然而,需要更多的研究来调查可能影响噬菌体疗法疗效的机制。一个重要的被忽视的方面是膜脂重塑对噬菌体结合能力的影响。铜绿假单胞菌当遇到磷胁迫时,膜脂会发生变化,磷胁迫是感染期间可能发生的环境扰动。脂质变化包括甘油磷脂被替代糖脂替代和含鸟氨酸氨基脂的过量产生。鉴于已知膜脂会影响膜蛋白的结构和功能,我们提出感染期间膜脂组成的变化可能会改变噬菌体结合和随后的噬菌体感染动力学。需要紧急优先考虑这些影响,以便为铜绿假单胞菌感染制定最有效的噬菌体治疗策略。
更新日期:2022-07-15
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