Mechanistic insights into the mode of action of anticandidal sesamol
Mechanistic insights into the mode of action of anticandidal sesamol
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DOI：
10.1016/j.micpath.2016.07.004
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发表时间：
2016-09-01
影响因子：
3.8
通讯作者：
Hameed, Saif
中科院分区：
文献类型：
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作者：
Ansari, Moiz A.;Fatima, Zeeshan;Hameed, Saif
以前我们已经破译了芝麻酚（Ses），一种从芝麻油中提取的酚类化合物，对人类真菌病原体白色念珠菌的抗真菌作用。为了更深入地了解可能涉及的机制，在Ses存在的情况下进行了转录分析，揭示了Ses阻碍白色念珠菌生长的各种靶点。我们观察到Ses扰乱了膜的完整性，证实了我们之前的观察结果，并显示出质膜atp酶活性的破坏。我们进一步研究了硒会导致形态学转变、生物膜形成和上皮细胞粘附受到抑制，这些都是致病所必需的重要毒力属性。有趣的是，Ses还会引起铁稳态的改变，如缺铁条件下的超敏反应、铁氧化铁酶测定和伴随的高亲和铁转运蛋白FTR2的上调。最后，我们评估了Ses导致线粒体功能缺陷和DNA修复机制。综上所述，作为一种可消耗的天然产物，有必要对其进行进一步的研究，以开发其作为有效的抗真菌剂。(C) 2016 Elsevier Ltd.版权所有。
Previously we have deciphered the antifungal effect of sesamol (Ses), a phenolic compound obtained from sesame oil, against human fungal pathogen Candida albicans. To gain deeper insights into the possible mechanisms involved, transcription profiling was done in presence of Ses which revealed various targets through which Ses was barricading the growth of C. albicans. We observed that Ses perturbs membrane integrity confirming our previous observations and displayed disrupted plasma membrane ATPase activity. We further investigated that Ses leads to inhibited morphological transition, biofilm formation and epithelial cell adhesion which are significant virulence attributes required for pathogenesis. Interestingly, Ses also causes amendment in iron homeostasis as revealed by hypersensitivity under iron deprivation, ferroxidase assay to estimate iron levels and concomitant upregulation of FTR2, a high affinity iron transporter. Finally we assessed that Ses causes defect in mitochondrial functioning and DNA repair mechanism. Together, being source of consumable natural product, further studies on Ses are warranted so that it can be exploited as effective antifungal agent. (C) 2016 Elsevier Ltd. All rights reserved.