Inhibition of biofilm- and hyphal- development, two virulent features of Candida albicans by secondary metabolites of an endophytic fungus Alternaria tenuissima having broad spectrum antifungal potential
Inhibition of biofilm- and hyphal- development, two virulent features of Candida albicans by secondary metabolites of an endophytic fungus Alternaria tenuissima having broad spectrum antifungal potential
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DOI：
10.1016/j.micres.2019.126386
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发表时间：
2020-02-01
影响因子：
6.7
通讯作者：
Mandal, Narayan Chandra
中科院分区：
文献类型：
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作者：
Chatterjee, Sohini;Ghosh, Ranjan;Mandal, Narayan Chandra
真菌对侵袭性念珠菌病和其他真菌感染常用抗真菌药物的耐药性正指导科学家寻找和开发新的抗真菌药物。从细花罗勒叶中分离到一株内生真菌Alternaria tenuissima OE7，该菌株对红色毛霉菌、石膏小孢子菌、寄生曲霉、黄曲霉、烟曲霉菌、白色念珠菌和热带毛霉菌等多种人类病原真菌均有抗真菌活性。耐热、不含蛋白质的抗真菌代谢物对所有测试的病原真菌产生抑制区。无细胞培养上清液的乙酸乙酯提取物对红曲霉和石膏霉的径向生长和分生孢子萌发均有抑制作用。最有趣的是，较低浓度(100-500µg/ml)的EA组分对白色念珠菌的生物被膜形成和菌丝发育均有抑制作用。从处理过的念珠菌细胞内释放的内容物和扫描电子显微镜观察表明，抗真菌代谢产物破坏了细胞。棋盘实验显示OE7的EA组分(150 mU g/ml)与氟康唑(30 mU g/ml)有协同作用，Sigma FIC为0.45。两个活性馏分，即。经薄层层析后得到的C带和G带对白色念珠菌具有抑制活性，其MIC值分别为80mU g/ml和130mU g/ml。GC-MS分析表明，每个活性组份中都含有大量的化合物。总体观察证明，分离株OE7作为生产抗真菌代谢物对抗人类致病真菌的有效候选者具有潜在的作用。
Fungal resistance against frequently used antifungal medicines used for invasive candidiasis and other fungal infections is directing scientist for searching and developing novel antifungal drugs. An endophytic fungal strain Alternaria tenuissima OE7 has been isolated from leaves of Ocimum tenuiflorum L. which showed antifungal activity against numbers of human pathogenic fungi including Trichophyton rubrum, Microsporum gypseum, Aspergillus parasiticus, A. flavus, A. fumigates, Candida albicans and C. tropicalis. Thermostable, non-proteinacious antifungal metabolites produced zones of inhibition against all pathogenic fungi tested. The ethyl acetate extract of the cell free supernatant was found inhibitory to the radial growth and conidial germination of T. rubrum and M. gypseum. It also showed cidal mode of action against C. albicans at a concentration of 1.0 mg/ml. Most interestingly, inhibition of biofilm formation and hyphal development of C. albicans were observed upon treatment with EA fraction at comparatively lower concentrations (100-500 mu g/ml). Release of intracellular contents from treated cells of Candida and scanning electron microscopic observation suggested cellular disruptions by antifungal metabolites. Checkerboard study revealed synergy between EA fraction of OE7 (150 mu g/ml) and fluconazole (30 mu g/ml) with Sigma FIC of 0.45. Two active fractions viz. band 'C' and band 'G' derived after thin layer chromatographic analysis showed inhibitory activity against C. albicans with MIC values of 80 mu g/ml and 130 mu g/ml respectively. GC-MS analysis suggested presence of numbers of compounds in each active fraction. Overall observations attest the prospective role of the isolate OE7 as a potent candidate for the production of antifungal metabolites against human pathogenic fungi.