BBSRC Midlands Integrative Biosciences Training Partnership, University of Warwick, Coventry, UK.
School of Life Sciences, University of Warwick, Coventry, UK.
Environ Microbiol. 2022 Oct;24(10):4533-4546. doi: 10.1111/1462-2920.16136. Epub 2022 Aug 14.
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.
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。它在医院感染、免疫功能低下的患者和囊性纤维化患者中尤为麻烦。抗生素耐药性（AMR）对全球健康构成巨大威胁，预计到 2050 年，将有 1000 万人死于耐药感染。噬菌体治疗是对抗 AMR 感染的一种有前途的疗法。然而，需要更多的研究来调查可能影响噬菌体治疗效果的机制。一个被忽视的重要方面是膜脂重塑对噬菌体结合能力的影响。当铜绿假单胞菌遇到磷胁迫时，会发生膜脂变化，这种环境干扰很可能在感染过程中发生。脂质变化包括甘油磷脂被替代为糖脂，以及鸟氨酸含氨基脂的过度产生。鉴于已知膜脂会影响膜蛋白的结构和功能，我们假设感染过程中膜脂组成的变化可能会改变噬菌体的结合和随后的噬菌体感染动力学。为了开发针对铜绿假单胞菌感染的最有效的噬菌体治疗策略，迫切需要优先考虑这些影响。
