Ting Darren Shu Jeng, Aung Thet Tun, Mayandi Venkatesh, Periayah Mercy Halleluyah, Goh Eunice Tze Leng, Muthu Mugil, Barathi Veluchamy Amutha, Mehta Jodhbir S, Tan Donald Tiang Hwee, Lakshminarayanan Rajamani
Academic Unit of Ophthalmology Department of Inflammation and Ageing, School of Immunity, Infection, and Inflammation, College of Medicine and Health, University of Birmingham, Birmingham, UK.
Birmingham and Midland Eye Centre, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
NPJ Antimicrob Resist. 2025 Sep 9;3(1):77. doi: 10.1038/s44259-025-00142-y.
Pseudomonas aeruginosa (PA) represents a major cause of antimicrobial resistance-related morbidity and mortality. The recent emergence of highly fatal infections, caused by carbapenem-resistant PA, has called for novel antimicrobial therapies and strategies. In this study, we highlight the therapeutic potential of ε-poly-L-lysine (εPL), an antimicrobial polymer for treating extensively-and pan-drug-resistant-PA. εPL displayed potent antimicrobial activity against all eight drug-resistant PA, including carbapenem- and polymyxin-resistant PA. It exhibited a low risk of AMR evolution, with no evidence of cross-resistance with polymyxin B (a last-line treatment for drug-resistant Gram-negative bacteria). We further demonstrated promising in vivo efficacy and safety of εPL against PA in a pre-clinical PA keratitis model, with comparable effects to topical levofloxacin (a gold standard treatment of infectious keratitis) in terms of clinical scoring, corneal health/thickness, and bacterial bioburden. In view of its broad-spectrum antimicrobial activity, low risk of AMR evolution and cross-resistance with existing last-line antibiotics, and general acceptance of safety when orally administered, εPL serves as a promising novel antimicrobial agent for further clinical development and translation to tackle antimicrobial resistance.
铜绿假单胞菌（PA）是导致与抗菌药物耐药性相关的发病和死亡的主要原因。近期，由耐碳青霉烯类PA引起的高度致命感染的出现，促使人们寻求新的抗菌治疗方法和策略。在本研究中，我们强调了ε-聚-L-赖氨酸（εPL）作为一种抗菌聚合物在治疗广泛耐药和泛耐药PA方面的治疗潜力。εPL对所有八种耐药PA均表现出强大的抗菌活性，包括耐碳青霉烯类和耐多粘菌素类PA。它显示出较低的抗菌药物耐药性演变风险，没有证据表明与多粘菌素B（耐药革兰氏阴性菌的一线治疗药物）存在交叉耐药性。我们还在临床前PA角膜炎模型中进一步证明了εPL对PA具有良好的体内疗效和安全性，在临床评分、角膜健康/厚度和细菌生物负荷方面，其效果与局部使用左氧氟沙星（感染性角膜炎的金标准治疗药物）相当。鉴于其广谱抗菌活性、较低的抗菌药物耐药性演变风险以及与现有一线抗生素无交叉耐药性，并且口服给药时安全性普遍可接受，εPL是一种有前景的新型抗菌剂，有望进一步开展临床研发并转化应用，以应对抗菌药物耐药性问题。
