دورية أكاديمية
ASLdC3: A Derivative of Acidic Sophorolipid Disrupts Mitochondrial Function, Induces ROS Generation, and Inhibits Biofilm Formation in Candida albicans .
| العنوان: | ASLdC3: A Derivative of Acidic Sophorolipid Disrupts Mitochondrial Function, Induces ROS Generation, and Inhibits Biofilm Formation in Candida albicans . |
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| المؤلفون: | Basotra SD; Biochemical Engineering Research and Process Development Centre (BERPDC), CSIR-Institute of Microbial Technology (IMTECH), Sector-39A, Chandigarh 160036, India., Kumari Y; Biochemical Engineering Research and Process Development Centre (BERPDC), CSIR-Institute of Microbial Technology (IMTECH), Sector-39A, Chandigarh 160036, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Vij M; Biochemical Engineering Research and Process Development Centre (BERPDC), CSIR-Institute of Microbial Technology (IMTECH), Sector-39A, Chandigarh 160036, India., Tyagi A; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.; GN Ramachandran Protein Centre, CSIR-Institute of Microbial Technology (IMTECH), Sector-39A, Chandigarh 160036, India., Sharma D; GN Ramachandran Protein Centre, CSIR-Institute of Microbial Technology (IMTECH), Sector-39A, Chandigarh 160036, India., Bhattacharyya MS; Biochemical Engineering Research and Process Development Centre (BERPDC), CSIR-Institute of Microbial Technology (IMTECH), Sector-39A, Chandigarh 160036, India. |
| المصدر: | ACS infectious diseases [ACS Infect Dis] 2024 Sep 13; Vol. 10 (9), pp. 3185-3201. Date of Electronic Publication: 2024 Aug 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: ACS Publications Country of Publication: United States NLM ID: 101654580 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-8227 (Electronic) Linking ISSN: 23738227 NLM ISO Abbreviation: ACS Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ACS Publications, [2015]- |
| مواضيع طبية MeSH: | Biofilms*/drug effects , Candida albicans*/drug effects , Candida albicans*/physiology , Antifungal Agents*/pharmacology , Antifungal Agents*/chemistry , Antifungal Agents*/chemical synthesis , Reactive Oxygen Species*/metabolism , Mitochondria*/drug effects , Microbial Sensitivity Tests*, Animals ; Humans ; Oleic Acids |
| مستخلص: | Fungal infections account for more than 140 million cases of severe and life-threatening conditions each year, causing approximately 1.7 million deaths annually. Candida albicans and related species are the most common human fungal pathogens, causing both superficial (mucosal and cutaneous) and life-threatening invasive infections (candidemia) with a 40-75% mortality rate. Among many virulence factors of Candida albicans , morphological transition from yeast to hyphae, secretion of hydrolytic enzymes, and formation of biofilms are considered to be crucial for pathogenicity. However, the arsenals for the treatment against these pathogens are restricted to only a few classes of approved drugs, the efficacy of which is being compromised by host toxicity, fungistatic activity, and the emergence of drug resistance. In this study, we have described the development of a molecule, exhibiting excellent antifungal activity (MIC 8 μg/mL), by tailoring acidic sophorolipids with aryl alcohols via enzyme catalysis. This novel derivative, ASLdC3, is a surface-active compound that lowers the surface tension of the air-water interface up to 2-fold before reaching the critical micelle concentration of 25 μg/mL. ASLdC3 exhibits excellent antibiofilm properties against Candida albicans and other nonalbicans Candida species. The molecule primarily exhibits its antifungal activity by perturbing mitochondrial function through the alteration of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS). The ROS damages fungal cell membrane function and cell wall integrity, eventually leading to cell death. ASLdC3 was found to be nontoxic in in vitro assay and nonhemolytic. Besides, it does not cause toxicity in the C. elegans model. Our study provides a valuable foundation for the potential of acidic sophorolipid as a nontoxic, biodegradable precursor for the design and synthesis of novel molecules for use as antimicrobial drugs as well as for other clinical applications. |
| فهرسة مساهمة: | Keywords: Candida albicans; fungal biofilm; novel antifungal agent; sophorolipid derivative |
| المشرفين على المادة: | 0 (Antifungal Agents) 0 (Reactive Oxygen Species) 0 (sophorolipid) 0 (Oleic Acids) |
| تواريخ الأحداث: | Date Created: 20240802 Date Completed: 20240913 Latest Revision: 20240913 |
| رمز التحديث: | 20240913 |
| DOI: | 10.1021/acsinfecdis.4c00155 |
| PMID: | 39093050 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 2373-8227 |
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| DOI: | 10.1021/acsinfecdis.4c00155 |