College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, China.
Appl Microbiol Biotechnol. 2020 Apr;104(8):3529-3540. doi: 10.1007/s00253-020-10462-w. Epub 2020 Feb 26.
Malassezia globosa is an opportunistic pathogen that causes various skin disorders, which disturbs people's life all the time, and conventional drugs are not completely satisfactory. Bacillomycin D (BD), an antifungal lipopeptide, could inhibit various fungi growth. However, the reports about its effect on M. globosa were not found yet. In this study, we showed that BD and BD-C16 (fatty acid chain had sixteen carbon atoms) completely inhibited growth of M. globosa at concentration of 64 μg/ml in 15 h, which was confirmed with the observation of irregular morphological change of M. globosa treated with BD. Significantly, the study on the working mechanism showed that BD induced cell death by changing cell membrane permeability and thus promoting the release of cellular contents, which may be mediated by the interaction between BD and ergosterol from membrane. Further study showed that BD reduced the overall content of cellular sterol, and interestingly, the expression of some genes involved in membrane and ergosterol synthesis were significantly upregulated, which was likely to be a feedback regulation. Besides, we found that BD had additive and synergistic effects with ketoconazole and amphotericin B, respectively, on inhibition of M. globosa, suggesting that combination use of BD with other commercial drugs could be a promising strategy to relieve skin disorders caused by M. globosa. KEY POINTS: • BD could efficiently inhibit the growth of M. globosa. • BD increases cell membrane permeability and thus promotes the release of cellular contents. • BD has additive or synergistic effect with other antifungal drugs.
球形马拉色菌是一种机会致病菌,可引起各种皮肤疾病,一直困扰着人们的生活,而常规药物并不完全令人满意。杆菌肽 D(BD)是一种抗真菌脂肽,可抑制多种真菌的生长。然而,目前尚未有关于其对球形马拉色菌影响的报道。在这项研究中,我们表明 BD 和 BD-C16(脂肪酸链有十六个碳原子)在 15 小时内完全抑制了浓度为 64μg/ml 的球形马拉色菌的生长,这从用 BD 处理的球形马拉色菌的不规则形态变化观察中得到了证实。值得注意的是,对作用机制的研究表明,BD 通过改变细胞膜通透性诱导细胞死亡,从而促进细胞内容物的释放,这可能是通过 BD 与膜中的麦角固醇相互作用介导的。进一步的研究表明,BD 降低了细胞甾醇的总含量,有趣的是,一些涉及膜和麦角固醇合成的基因的表达显著上调,这可能是一种反馈调节。此外,我们发现 BD 分别与酮康唑和两性霉素 B 具有相加和协同作用,抑制球形马拉色菌,这表明 BD 与其他商业药物联合使用可能是缓解由球形马拉色菌引起的皮肤疾病的一种有前途的策略。关键点:
BD 能有效抑制 M. globosa 的生长。
BD 增加细胞膜通透性,从而促进细胞内容物的释放。
BD 与其他抗真菌药物具有相加或协同作用。