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抗氟康唑白色念珠菌羊毛甾醇14-α-去甲基化酶的抗坏血酸体外和计算机模拟分析

In Vitro and In Silico Analysis of Ascorbic Acid Towards Lanosterol 14-α-Demethylase Enzyme of Fluconazole-Resistant Candida albicans.

作者信息

Ganeshkumar Arumugam, Suvaithenamudhan Suvaiyarasan, Rajaram Rajendran

机构信息

DNA Barcoding and Marine Genomics Laboratory, Department of Marine Science, Bharathidasan University, Tiruchchirappalli, Tamil Nadu, 620 024, India.

Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchchirappalli, Tamil Nadu, 620 024, India.

出版信息

Curr Microbiol. 2021 Jan;78(1):292-302. doi: 10.1007/s00284-020-02269-9. Epub 2020 Nov 10.

DOI:10.1007/s00284-020-02269-9
PMID:33170381
Abstract

Antibiotic resistance is one of the major concerns and the biggest threats to the world population. The incidents of antibiotic resistance in Candida spp. were frequently recorded. In the present investigation, antifungal potential of ascorbic acid (AA) was evaluated. According to the in vitro analysis, the zone of inhibition of AA (24.75 ± 0.35 mm) against C. albicans was greater as compared to other vitamins tested. AA significantly modulate the growth of C. albicans at 25 mg/ml. The highest percentage (94.67%) of cell viability was observed in untreated cells, and low cell viability (29.36%) was observed in cells treated with 50 mg/ml of AA (2 × MIC). Further, AO/EB (acridine orange/ethidium bromide), propidium iodide staining, and real-time qPCR confirmed the loss of membrane integrity due to membrane lesions that caused cell death. Lanosterol 14-α-demethylase (L-14α-DM) is the product of ERG11 and acted as superior drug target of C. albicans. Molecular docking analysis confirmed that active interaction of ascorbic acid with L-14α-DM. Based on the present investigation, the efficiency of AA was effectively proved through the in vitro and in silico analysis. This finding has evidenced the effectiveness of AA as a potential candidate against C. albicans.

摘要

抗生素耐药性是全球人口面临的主要问题之一,也是最大威胁之一。念珠菌属中抗生素耐药性事件屡有记录。在本研究中,评估了抗坏血酸(AA)的抗真菌潜力。根据体外分析,与其他测试的维生素相比,AA对白色念珠菌的抑菌圈(24.75±0.35毫米)更大。在25毫克/毫升时,AA能显著调节白色念珠菌的生长。未处理细胞的细胞活力百分比最高(94.67%),而用50毫克/毫升AA(2×MIC)处理的细胞细胞活力较低(29.36%)。此外,吖啶橙/溴化乙锭(AO/EB)、碘化丙啶染色和实时定量PCR证实,由于膜损伤导致细胞死亡,细胞膜完整性丧失。羊毛甾醇14-α-脱甲基酶(L-14α-DM)是ERG11的产物,是白色念珠菌的主要药物靶点。分子对接分析证实抗坏血酸与L-14α-DM存在活性相互作用。基于本研究,通过体外和计算机模拟分析有效证明了AA的有效性。这一发现证明了AA作为抗白色念珠菌潜在候选药物的有效性。

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