Department of Pathogenic Microbiology & Immunology, School of Basic Medical Sciences, Xi'an Jiao Tong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, China.
Clinical Laboratory, The Second Hospital of Weinan, 2 East Chaoyang Street, Weinan, 714000, China.
Microb Biotechnol. 2022 Feb;15(2):499-512. doi: 10.1111/1751-7915.13875. Epub 2021 Jun 24.
Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.
红色毛癣菌是导致大多数皮肤癣菌病的原因。目前用于治疗皮肤癣菌病的系统性和局部性抗真菌药物通常比较繁琐,有时效果并不理想。光动力抗菌疗法(aPDT)是一种非侵入性的替代方法,适用于治疗浅表真菌感染。本研究调查了大黄素(AE)作为一种天然光敏剂(PS)对红色毛癣菌微孢子的体外光动力灭活效果和作用,并评估了 AE 介导的 aPDT 对红色毛癣菌引起的体癣和体外甲癣的治疗效果。通过 MTT 测定评估 AE 对红色毛癣菌微孢子的光动力抗菌功效。研究了 AE 介导的 aPDT 对红色毛癣菌生长的抑制作用。通过显微镜和流式细胞术研究了 AE 介导的 aPDT 对微孢子细胞结构和表面的损伤以及细胞内 ROS 的产生。在红色毛癣菌引起的豚鼠体癣模型和体外甲癣模型中评估了 AE 介导的 aPDT 对皮肤癣菌病的治疗效果。AE 介导的 aPDT 以光能剂量依赖的方式有效灭活红色毛癣菌微孢子,对红色毛癣菌的生长表现出强烈的抑制作用。显微镜图像表明,AE 主要靶向细胞器,并通过产生大量细胞内 ROS 对微孢子的细胞质造成损伤。AE 介导的 aPDT 对豚鼠模型中的红色毛癣菌引起的体癣和体外甲癣均具有有效的治疗效果。结果表明,AE 是一种有潜力的用于治疗红色毛癣菌引起的皮肤癣菌病的 PS,但需要提高其在皮肤和指甲中的通透性。