Novel antifungal agents are required against pathogenic fungi such as Candida albicans. We report the anticandidal activity of battacin lipopeptide antibiotics with previously unexplored antifungal activity. From amongst sixteen battacin lipopeptides tested against C. alibicans (SC5314) the 4-methyl hexanoyl conjugated trimeric lipopeptide 13 emerged as the lead candidate with a MIC of 6.25 μM and negligible haemolysis of mouse red blood cells. The potency of this lipopeptide was maintained under acidic conditions. Additionally, antifungal activity was further enhanced with amphotericin B at its non-haemolytic concentrations. Herein we have demonstrated for the first time that battacin lipopeptides prevent C. albicans biofilm colonisation as well as inhibit pre-formed biofilms of this fungal pathogen. XTT biofilm assays revealed that 13 prevented colonisation of C. albicans biofilms at its MIC (6.25 μM) and, at a higher concentration, eradicated 24 h (25 μM) and 48 h (62.5 μM) old preformed biofilms. In comparison, we found that amphotericin at much lower concentrations prevented biofilm colonisation (0.78 μM) and inhibited 24 h old preformed biofilms (6.25 μM), however was completely inactive against 48 h old preformed biofilms. Thus, lipopeptide 13 is more effective than amphotericin at eradicating more mature C. albicans biofilms. The membrane lytic mechanism of action of compound 13 was validated by a colorimetric assay using lipid vesicles mimicking fungal membranes in which compound 13 effected an immediate dark purple to red colour transition of suspended vesicles upon peptide interaction. In addition, TEM images of C. albicans cells exposed to 13 showed clearly disrupted cellular membranes. Interestingly, compound 13 increased the endogenous generation of reactive oxygen species (ROS) in a concentration dependent manner. In the presence of an antioxidant, ascorbic acid, ROS production was diminished yet antifungal activity persisted, possibly indicating that ROS production is a secondary effect from membrane lysis caused by lipopeptide 13. The lipopeptide was non-haemolytic against mouse red blood cells at the highest tested concentration (1 mM).

需要新型的抗真菌剂来抵抗病原真菌，例如白色念珠菌。我们报告了巴他新脂肽抗生素的抗cancandal活动与以前未开发的抗真菌活性。在针对阿里巴球梭菌（SC5314）测试的16种battacin脂肽中，以MIC为6.25μM且小鼠红细胞的溶血作用可忽略的4甲基己酰基缀合的三聚脂肽13成为主要候选药物。该脂肽的效力保持在酸性条件下。此外，两性霉素B在非溶血浓度下的抗真菌活性进一步增强。在这里，我们首次证明了巴他新脂肽可以预防白色念珠菌生物膜定殖以及抑制这种真菌病原体的预先形成的生物膜。XTT生物膜测定表明，有13种微生物阻止了白色念珠菌生物膜在其MIC（6.25μM）上的定植，并在较高浓度下消除了24 h（25μM）和48 h（62.5μM）的旧预制生物膜。相比之下，我们发现低浓度的两性霉素可防止生物膜定殖（0.78μM）并抑制24 h的预制生物膜（6.25μM），但是对48 h的预制生物膜完全没有活性。因此，在消除更成熟的白色念珠菌生物膜方面，脂肽13比两性霉素更有效。化合物13的膜分解作用机理通过使用比拟脂膜的脂质膜模拟真菌膜的比色测定法，通过化合物比色法验证了化合物13在肽相互作用后立即使悬浮的囊泡由暗紫色转变为红色。另外，暴露于13的白色念珠菌细胞的TEM图像显示出明显破坏的细胞膜。有趣的是，化合物13以浓度依赖性方式增加了活性氧（ROS）的内源性产生。在存在抗氧化剂抗坏血酸的情况下，ROS的产生减少，但抗真菌活性持续存在，这可能表明ROS的产生是脂肽13引起的膜裂解的次要作用。。脂肽在最高测试浓度（1 mM）下对小鼠红细胞无溶血作用。