白色念珠菌
麦角甾醇
甲壳素
细胞壁
化学
微生物学
肉汤微量稀释
白色体
生物化学
生物
细胞生物学
生物物理学
抗菌剂
最小抑制浓度
壳聚糖
作者
Venkata Saibabu,Zeeshan Fatima,Luqman Ahmad Khan,Saif Hameed
出处
期刊:Infectious disorders drug targets
[Bentham Science]
日期:2021-05-01
卷期号:21 (3): 405-415
被引量:4
标识
DOI:10.2174/1871526520666200702134110
摘要
Background: Considering the emergence of multidrug resistance (MDR) in prevalent human fungal pathogen, Candida albicans, there is parallel spurt in development of novel strategies aimed to disrupt MDR. Compounds from natural resources could be exploited as efficient antifungal drugs owing to their structural diversity, cost effectiveness and negligible side effects. Objective: The present study elucidates the antifungal mechanisms of Vanillin (Van), a natural food flavoring agent against Candida albicans. Methods: Antifungal activities were assessed by broth microdilution and spot assays. Membrane and cell wall perturbations were studied by PI uptake, electron microscopy, plasma membrane H+ extrusion activity and estimation of ergosterol and chitin contents. Mitochondrial functioning was studied by growth on non-fermentable carbon sources, rhodamine B labeling and using retrograde signaling mutants. Gene expressions were validated by semi-quantitative RT-PCR. Results: We observed that the antifungal activity of Van was not only limited to clinical isolates of C. albicans but also against non-albicans species of Candida. Mechanistic insights revealed effect of Van on cell surface integrity as evident from hypersensitivity against membrane perturbing agent SDS, depleted ergosterol levels, transmission electron micrographs and diminished plasma membrane H+ extrusion activity. In addition, spot assays with cell wall perturbing agents, scanning electron micrographs, delayed sedimentation rate and lower chitin content further substantiate cell wall damage by Van. Furthermore, Van treated cells underwent mitochondrial dysfunctioning via impaired retrograde signaling leading to abrogated iron homeostasis and DNA damage. All the perturbed phenotypes were also validated by RT-PCR depicting differential regulation of genes (NPC2, KRE62, FTR2 and CSM3) in response to Van. Conclusion: Together, our results suggested that Van is promising antifungal agent that may be advocated for further investigation in therapeutic strategies to treat Candida infections.
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