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

被引:13
作者
Ganeshkumar, Arumugam [1 ]
Suvaithenamudhan, Suvaiyarasan [2 ]
Rajaram, Rajendran [1 ]
机构
[1] Bharathidasan Univ, Dept Marine Sci, DNA Barcoding & Marine Genom Lab, Tiruchirappalli 620024, Tamil Nadu, India
[2] Bharathidasan Univ, Sch Life Sci, Dept Bioinformat, Tiruchirappalli 620024, Tamil Nadu, India
关键词
VITAMIN-C; MECHANISMS; INHIBITORS; VIRULENCE; SEPSIS;
D O I
10.1007/s00284-020-02269-9
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 x 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-alpha-demethylase (L-14 alpha-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-14 alpha-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.
引用
收藏
页码:292 / 302
页数:11
相关论文
共 47 条
[1]   Amino Acid Substitutions at the Major Insertion Loop of Candida albicans Sterol 14alpha-Demethylase Are Involved in Fluconazole Resistance [J].
Alvarez-Rueda, Nidia ;
Fleury, Audrey ;
Morio, Florent ;
Pagniez, Fabrice ;
Gastinel, Louis ;
Le Pape, Patrice .
PLOS ONE, 2011, 6 (06)
[2]   Overexpression of CDR1 and CDR2 Genes Plays an Important Role in Fluconazole Resistance in Candida albicans with G487T and T916C Mutations [J].
Chen, L. M. ;
Xu, Y. H. ;
Zhou, C. L. ;
Zhao, J. ;
Li, C. Y. ;
Wang, R. .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2010, 38 (02) :536-545
[3]   How to bolster the antifungal pipeline [J].
Denning, David W. ;
Bromley, Michael J. .
SCIENCE, 2015, 347 (6229) :1414-1416
[4]   Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans [J].
Douglas, Lois M. ;
Konopka, James B. .
JOURNAL OF MICROBIOLOGY, 2016, 54 (03) :178-191
[5]   Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes [J].
Friesner, Richard A. ;
Murphy, Robert B. ;
Repasky, Matthew P. ;
Frye, Leah L. ;
Greenwood, Jeremy R. ;
Halgren, Thomas A. ;
Sanschagrin, Paul C. ;
Mainz, Daniel T. .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (21) :6177-6196
[6]   New insight of red seaweed derived Callophycin A as an alternative strategy to treat drug resistance vaginal candidiasis [J].
Ganeshkumar, Arumugam ;
Suvaithenamudhan, Suvaiyarasan ;
Elanthamilan, Elaiyappillai ;
Arun, Ganesan ;
Dileepan, Gowrisivam Anbusivam Bharathi ;
Prabhusaran, Nagarajan ;
Rajaram, Rajendran .
BIOORGANIC CHEMISTRY, 2020, 104
[7]   In Vitro Antifungal Activity of a Medicinal Plant Extract Mixture Against Candida Species Isolated from Patients with Oral Stomatitis [J].
Genc, Gonca Erkose ;
Erdogan, Ozcan ;
Demir, Candan ;
Kisa, Ozgul ;
Satana, Dilek .
IRANIAN RED CRESCENT MEDICAL JOURNAL, 2019, 21 (04)
[8]   Antifungal Activity and Potential Mechanism of N-Butylphthalide Alone and in Combination With Fluconazole Against Candida albicans [J].
Gong, Ying ;
Liu, Weiguo ;
Huang, Xin ;
Hao, Lina ;
Li, Yiman ;
Sun, Shujuan .
FRONTIERS IN MICROBIOLOGY, 2019, 10
[9]   Identifying and Characterizing Binding Sites and Assessing Druggability [J].
Halgren, Thomas A. .
JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2009, 49 (02) :377-389
[10]   New method for fast and accurate binding-site identification and analysis [J].
Halgren, Tom .
CHEMICAL BIOLOGY & DRUG DESIGN, 2007, 69 (02) :146-148