Wang Qifei, Yang Junlin, Xing Malcolm, Li Bingyun
Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Microorganisms. 2024 Aug 15;12(8):1682. doi: 10.3390/microorganisms12081682.
Preventing infection is a critical clinical challenge; however, the extensive use of antibiotics has resulted in remarkably increased antibiotic resistance. A variety of antibiotic alternatives including antimicrobial peptides (AMPs) have been studied. Unfortunately, like most conventional antibiotics, most current AMPs have shown significantly high toxicity toward the host, and therefore induce compromised host responses that may lead to negative clinical outcomes such as delayed wound healing. In this study, one of the AMPs with a short length of nine amino acids was first identified via machine learning to present potentially low cytotoxicity, and then synthesized and validated in vitro against both bacteria and mammalian cells. It was found that this short AMP presented strong and fast-acting antimicrobial properties against bacteria like , one of the most common bacteria clinically, and it targeted and depolarized bacterial membranes. This AMP also demonstrated significantly lower (e.g., 30%) toxicity toward mammalian cells like osteoblasts, which are important cells for new bone formation, compared to conventional antibiotics like gentamicin, vancomycin, rifampin, cefazolin, and fusidic acid at short treatment times (e.g., 2 h). In addition, this short AMP demonstrated relatively low toxicity, similar to osteoblasts, toward an epithelial cell line like BEAS-2B cells.
预防感染是一项关键的临床挑战；然而，抗生素的广泛使用已导致抗生素耐药性显著增加。人们已经研究了包括抗菌肽（AMPs）在内的多种抗生素替代品。不幸的是，与大多数传统抗生素一样，目前大多数抗菌肽对宿主表现出显著的高毒性，因此会引发宿主反应受损，这可能导致诸如伤口愈合延迟等负面临床结果。在本研究中，首先通过机器学习鉴定出一种长度为九个氨基酸的抗菌肽，其具有潜在的低细胞毒性，然后进行合成并在体外针对细菌和哺乳动物细胞进行验证。结果发现，这种短抗菌肽对临床上最常见的细菌之一等细菌具有强大且速效的抗菌特性，并且它靶向细菌膜并使其去极化。与庆大霉素、万古霉素、利福平、头孢唑林和夫西地酸等传统抗生素相比，在短治疗时间（例如2小时）内，这种抗菌肽对成骨细胞等哺乳动物细胞（成骨细胞是新骨形成的重要细胞）的毒性也显著更低（例如30%）。此外，这种短抗菌肽对BEAS - 2B细胞等上皮细胞系的毒性相对较低，与成骨细胞相似。
