Gil Joel, Pastar Irena, Houghten Richard A, Padhee Shruti, Higa Alexander, Solis Michael, Valdez Jose, Head Cheyanne R, Michaels Heather, Lenhart Brian, Simms Colin, Williams Brandon, Cudic Predrag, Davis Stephen C
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Coral Gables, FL, United States.
Torrey Pines Institute for Molecular Studies, San Diego, CA, United States.
Front Microbiol. 2021 Jul 23;12:708904. doi: 10.3389/fmicb.2021.708904. eCollection 2021.
Both acute and chronic cutaneous wounds are often difficult to treat due to the high-risk for bacterial contamination. Once hospitalized, open wounds are at a high-risk for developing hospital-associated infections caused by multi drug-resistant bacteria such as and . Treating these infections is challenging, not only because of antibiotic resistance, but also due to the production of biofilms. New treatment strategies are needed that will help in both stimulating the wound healing process, as well as preventing and eliminating bacterial wound infections. Fusaricidins are naturally occurring cyclic lipopeptides with antimicrobial properties that have shown to be effective against a variety of fungi and Gram-positive bacteria, with low toxicity. Continuing with our efforts toward the identification of novel cyclic lipopeptides Fusaricidin analogs, herein we report the synthesis and evaluation of the antimicrobial activity for two novel cyclic lipopeptides (CLP), CLP 2605-4 and CLP 2612-8.1 against methicillin resistant and , respectively, in porcine full thickness wound model. Both CLPs were able to reduce bacterial counts by approximately 3 log CFU/g by the last assessment day. Peptide 2612-8.1 slightly enhanced the wound healing, however, wounds treated with peptide 2605-4, have shown higher levels of inflammation and impaired wound healing process. This study highlights the importance of identifying new antimicrobials that can combat bacterial infection while not impeding tissue repair.
由于存在细菌污染的高风险，急性和慢性皮肤伤口通常都难以治疗。一旦住院，开放性伤口就极易发生由耐多药细菌（如 和 ）引起的医院相关感染。治疗这些感染具有挑战性，不仅是因为抗生素耐药性，还由于生物膜的产生。需要新的治疗策略，既能促进伤口愈合过程，又能预防和消除伤口细菌感染。镰刀菌素是具有抗菌特性的天然环状脂肽，已证明对多种真菌和革兰氏阳性菌有效，且毒性低。为继续致力于鉴定新型环状脂肽镰刀菌素类似物，在此我们报告了两种新型环状脂肽（CLP），即CLP 2605 - 4和CLP 2612 - 8.1对耐甲氧西林的 和 的抗菌活性的合成及评估，评估是在猪全层伤口模型中进行的。到最后评估日时，两种CLP都能够将细菌计数降低约3 log CFU/g。肽2612 - 8.1对伤口愈合有轻微促进作用，然而，用肽2605 - 4处理的伤口显示出更高程度的炎症，且伤口愈合过程受损。这项研究强调了鉴定既能对抗细菌感染又不妨碍组织修复的新型抗菌剂的重要性。
