{"title":"Hydroxychloroquine an Antimalarial Drug, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Multitargeting","authors":"Sargun Tushar Basrani, Tanjila Chandsaheb Gavandi, Shivani Balasaheb Patil, Nandkumar Subhash Kadam, Dhairyasheel Vasantrao Yadav, Sayali Ashok Chougule, Sankunny Mohan Karuppayil, Ashwini Khanderao Jadhav","doi":"10.1007/s12275-024-00111-6","DOIUrl":null,"url":null,"abstract":"<p><i>Candida albicans</i> is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of <i>C. albicans</i> can progress to systemic infections in the worst situation<i>.</i> This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against <i>C. albicans</i>. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of <i>C. albicans</i> significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC<sub>50</sub>) of HCQ for <i>C. albicans</i> adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of <i>C. albicans</i> in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the <i>C. albicans</i> cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of <i>SOD2</i>, <i>SOD1</i>, and <i>CAT1</i> genes after HCQ treatment, while genes like <i>HWP1</i>, <i>RAS1</i>, <i>TEC1</i>, and <i>CDC 35</i> were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of <i>C. albicans</i> after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.</p>","PeriodicalId":16546,"journal":{"name":"Journal of Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12275-024-00111-6","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Candida albicans is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of C. albicans can progress to systemic infections in the worst situation. This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against C. albicans. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of C. albicans significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC50) of HCQ for C. albicans adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of C. albicans in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the C. albicans cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of SOD2, SOD1, and CAT1 genes after HCQ treatment, while genes like HWP1, RAS1, TEC1, and CDC 35 were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of C. albicans after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.
期刊介绍:
Publishes papers that deal with research on microorganisms, including archaea, bacteria, yeasts, fungi, microalgae, protozoa, and simple eukaryotic microorganisms. Topics considered for publication include Microbial Systematics, Evolutionary Microbiology, Microbial Ecology, Environmental Microbiology, Microbial Genetics, Genomics, Molecular Biology, Microbial Physiology, Biochemistry, Microbial Pathogenesis, Host-Microbe Interaction, Systems Microbiology, Synthetic Microbiology, Bioinformatics and Virology. Manuscripts dealing with simple identification of microorganism(s), cloning of a known gene and its expression in a microbial host, and clinical statistics will not be considered for publication by JM.