Sodium lignosulfonate inhibits multiple virulent proteins of human fungal pathogen Candida albicans

IF 2.3 3区 生物学 Q3 MICROBIOLOGY
Anubhuti Jha, Awanish Kumar
{"title":"Sodium lignosulfonate inhibits multiple virulent proteins of human fungal pathogen Candida albicans","authors":"Anubhuti Jha,&nbsp;Awanish Kumar","doi":"10.1007/s00203-024-04201-2","DOIUrl":null,"url":null,"abstract":"<div><p>Systemic mycoses, particularly those caused by Candida albicans, represent a serious global health concern due to rising multidrug resistance and limited treatment options. This study explores the antifungal potential of sodium lignosulfonate (LIG), a natural phenolic compound, as a multitarget therapeutic agent against various virulence proteins of C. albicans and other pathogenic <i>Candida</i> species. The objective of this study was to further evaluate its multiple-targeting/polypharmacological potential with plausible mode of action against <i>C. albicans</i>. At first, LIG was subjected to in-silico analysis to acquire preliminary knowledge about its multiple targeting potential. Subsequently, some biochemical analyses were performed to demonstrate its fungicidal activity. In-vitro analysis (plasma membrane permeation, ROS production, chitin depletion study) was performed to further validate its promising multiple-targeting/polypharmacological potential and revealed its mechanism of action. Homology modeling and docking studies revealed that LIG effectively binds to critical <i>C. albicans</i> proteins, including ERG1, ERG11, FKS1, CHS3, CLB2, and CEK1. The docking scores indicated strong interactions, supporting LIG’s potential to inhibit multiple virulence factors With ROS production we could confirm the involvement of apoptosis. Time-kill assays confirmed the antifungal effect of LIG against <i>C. albicans</i>, <i>C. glabrata</i>, <i>C. tropicalis</i>, and <i>C. parapsilosis</i>. LIG demonstrated a &gt; 3-log10 reduction in CFU/mL, and in combination with fluconazole, it showed synergistic activity, particularly reducing CFU in <i>C. dubliniensis</i> by 2.5-fold compared to fluconazole alone. The chitin depletion assay has reported a decrease in levels of chitin which indicates another aspect of LIG’s mode of action. This study reveals LIG as a potent and persuasive natural antifungal agent that targets multiple proteins of <i>Candida</i>. This revelation might impact the direction of potent antifungal agent development by aiming multiple targets of fungal pathogens simultaneously.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"207 1","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00203-024-04201-2.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Microbiology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s00203-024-04201-2","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Systemic mycoses, particularly those caused by Candida albicans, represent a serious global health concern due to rising multidrug resistance and limited treatment options. This study explores the antifungal potential of sodium lignosulfonate (LIG), a natural phenolic compound, as a multitarget therapeutic agent against various virulence proteins of C. albicans and other pathogenic Candida species. The objective of this study was to further evaluate its multiple-targeting/polypharmacological potential with plausible mode of action against C. albicans. At first, LIG was subjected to in-silico analysis to acquire preliminary knowledge about its multiple targeting potential. Subsequently, some biochemical analyses were performed to demonstrate its fungicidal activity. In-vitro analysis (plasma membrane permeation, ROS production, chitin depletion study) was performed to further validate its promising multiple-targeting/polypharmacological potential and revealed its mechanism of action. Homology modeling and docking studies revealed that LIG effectively binds to critical C. albicans proteins, including ERG1, ERG11, FKS1, CHS3, CLB2, and CEK1. The docking scores indicated strong interactions, supporting LIG’s potential to inhibit multiple virulence factors With ROS production we could confirm the involvement of apoptosis. Time-kill assays confirmed the antifungal effect of LIG against C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. LIG demonstrated a > 3-log10 reduction in CFU/mL, and in combination with fluconazole, it showed synergistic activity, particularly reducing CFU in C. dubliniensis by 2.5-fold compared to fluconazole alone. The chitin depletion assay has reported a decrease in levels of chitin which indicates another aspect of LIG’s mode of action. This study reveals LIG as a potent and persuasive natural antifungal agent that targets multiple proteins of Candida. This revelation might impact the direction of potent antifungal agent development by aiming multiple targets of fungal pathogens simultaneously.

木质素磺酸钠抑制人类真菌病原体白色念珠菌的多种毒力蛋白
系统性真菌病,特别是由白色念珠菌引起的真菌病,由于多药耐药性上升和治疗选择有限,是一个严重的全球卫生问题。本研究探讨了木质素磺酸钠(LIG)作为一种天然酚类化合物,对白色念珠菌和其他致病性念珠菌多种毒力蛋白的多靶点治疗剂的抗真菌潜力。本研究的目的是进一步评估其对白色念珠菌的多靶点/多药理学潜力和合理的作用方式。首先,对LIG进行了计算机分析,以获得其多重靶向潜力的初步知识。随后,进行了一些生化分析,以证明其杀真菌活性。体外分析(质膜渗透、ROS生成、几丁质消耗研究)进一步验证了其具有多靶点/多药理潜力,并揭示了其作用机制。同源性建模和对接研究表明,LIG可有效结合关键的白色念珠菌蛋白,包括ERG1、ERG11、FKS1、CHS3、CLB2和CEK1。对接评分显示出强烈的相互作用,支持LIG抑制多种毒力因子的潜力。我们可以证实ROS的产生与细胞凋亡有关。时间杀伤试验证实了LIG对白色念珠菌、光秃念珠菌、热带念珠菌和副枯枝念珠菌的抗真菌作用。LIG演示了一个>;CFU/mL降低3-log10,且与氟康唑联用时表现出协同作用,尤其与氟康唑单用相比,可使dubliniensis CFU降低2.5倍。几丁质消耗测定报告了几丁质水平的下降,这表明了LIG作用模式的另一个方面。本研究揭示了LIG是一种有效的、有说服力的天然抗真菌剂,可靶向念珠菌的多种蛋白质。这一发现可能会影响同时针对真菌病原体的多靶点开发有效的抗真菌药物的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Archives of Microbiology
Archives of Microbiology 生物-微生物学
CiteScore
4.90
自引率
3.60%
发文量
601
审稿时长
3 months
期刊介绍: Research papers must make a significant and original contribution to microbiology and be of interest to a broad readership. The results of any experimental approach that meets these objectives are welcome, particularly biochemical, molecular genetic, physiological, and/or physical investigations into microbial cells and their interactions with their environments, including their eukaryotic hosts. Mini-reviews in areas of special topical interest and papers on medical microbiology, ecology and systematics, including description of novel taxa, are also published. Theoretical papers and those that report on the analysis or ''mining'' of data are acceptable in principle if new information, interpretations, or hypotheses emerge.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信