In Vitro and In Vivo Evaluation of Small Cationic Abiotic Lipopeptides as Novel Antifungal Agents

Abstract

We investigated the antifungal potential of short lipopeptides against clinical fungal isolates with an objective to evaluate their clinical feasibility. All tested lipopeptides exhibit good antifungal activity with negligible difference between the MICs against susceptible and drug-resistant clinical fungal isolates. The MTT assay results revealed the lower cytotoxicity of lipopeptides toward mammalian cells (NRK-52E). In particular, LP24 displayed highest potency against most of the tested fungal isolates with MICs in the range of 1.5-4.5 μg/mL. Calcein dye leakage experiments with model membrane suggested the membrane-active mode of action for LP24. Extending our work from model membranes to intact Aspergillus fumigatus in scanning electron micrographs, we could visualize surface perturbation caused by LP24. LP24 (5 mg/kg) significantly reduces the A. fumigatus burden among the various organs of infected animals, and 70% of the infected mice survived when observed for 28 days. This study underscores the potential of small cationic abiotic lipopeptides to develop into the next-generation antimicrobial therapy.

Эволюционное Развитие И Структурное Разнообразие Природных Антимикробных Пептидов, Пептидомиметиков И Катионных Амфифилов На Основе Аминокислот

“…При этом наблюдается более низкий уровень цитотоксичности и гемолитической активности, нежели у известных средств бензалкония хлорида и цетримида при сопоставимом уровне минимальной ингибирующей концентрации [45]. Дипептидомиметики [46] и липопептиды с остатками L-орнитина или L-аргинина, в количестве от 2 до 5, проявляют высокую антимикробную активность с МИК 1,5-4,5 мкг/мл и 1,56-6,25 мкг/мл, соответственно [47,48].…”