Department of Microbial Pathogenesis and Immunology, Texas A&M School of Medicine, Bryan, TX, USA.
Institute of Immunology & Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Commun Biol. 2024 Aug 22;7(1):1033. doi: 10.1038/s42003-024-06725-1.
The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30-60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.
耐药性的兴起已成为全球性危机，每年有超过 100 万人死于耐药菌感染。铜绿假单胞菌尤其仍是一个严重的问题，由于复杂的耐药机制，目前导致美国每年超过 32000 例多重耐药（MDR）感染和 2000 多人死亡，而耐药菌的出现已经变得非常普遍，但在过去的 40 多年里，新的有用药物类别的发现一直受到限制。我们发现一种潜在的新型治疗药物，肽模拟物 TM5，可有效杀灭铜绿假单胞菌，并且在哺乳动物细胞中的毒性足够低，可用于治疗感染。有趣的是，TM5 比传统抗生素更有效地杀死铜绿假单胞菌，在体外 30-60 分钟内，并且对包括广泛耐药株在内的多种临床分离株有效。在体内，与未治疗的小鼠相比，TM5 在 24 小时内显著降低了肺部的细菌负荷，并且几乎没有不良反应。综上所述，这些观察结果表明，TM5 有望成为治疗 MDR 铜绿假单胞菌呼吸道感染的替代疗法。
