Vikas Kumar Somani, Somya Aggarwal, V S Radhakrishnan, Tulika Prasad, Rakesh Bhatnagar
{"title":"Investigating inhibitory effect of sterol targeting compounds against B. anthracis: Membrane microdomain a probable target.","authors":"Vikas Kumar Somani, Somya Aggarwal, V S Radhakrishnan, Tulika Prasad, Rakesh Bhatnagar","doi":"10.1016/j.resmic.2025.104351","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the role of membrane microdomains (MMd) in virulence of Bacillus anthracis by assessing the effects of known antifungal compounds, referred to as raft-associated lipid biosynthesis inhibitors (RALBIs), on its pathophysiology.</p><p><strong>Materials and methods: </strong>FDA-approved antifungal compounds representing three distinct classes-azoles (ketoconazole), allylamines (terbinafine), and polyenes (nystatin), were tested against B. anthracis. These compounds target different enzymes involved in MMd-associated lipid biosynthesis. Their impact on sporulation, toxin secretion, macrophage interaction, bio-signaling, cell envelope fluidity, and biofilm formation was examined. Additionally, their synergistic potential with conventional antibiotics was evaluated.</p><p><strong>Results: </strong>RALBIs markedly attenuated the pathogenic traits of B. anthracis, including reduced macrophage association, diminished toxin secretion, and impaired sporulation. Treatment also altered growth kinetics, morphology, biofilm development and cell envelope fluidity. Importantly, the combination of RALBIs with erythromycin significantly reduced its minimum inhibitory concentration (MIC) against B. anthracis.</p><p><strong>Conclusion: </strong>These findings highlight membrane microdomains as crucial regulators of virulence in B. anthracis and identify RALBIs as promising adjunctive agents. By targeting MMd, sterol inhibitors disrupt multiple pathogenic pathways and enhance antibiotic efficacy, underscoring their potential as novel antibacterial strategies.</p>","PeriodicalId":21098,"journal":{"name":"Research in microbiology","volume":" ","pages":"104351"},"PeriodicalIF":3.4000,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research in microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.resmic.2025.104351","RegionNum":4,"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
Purpose: This study aimed to evaluate the role of membrane microdomains (MMd) in virulence of Bacillus anthracis by assessing the effects of known antifungal compounds, referred to as raft-associated lipid biosynthesis inhibitors (RALBIs), on its pathophysiology.
Materials and methods: FDA-approved antifungal compounds representing three distinct classes-azoles (ketoconazole), allylamines (terbinafine), and polyenes (nystatin), were tested against B. anthracis. These compounds target different enzymes involved in MMd-associated lipid biosynthesis. Their impact on sporulation, toxin secretion, macrophage interaction, bio-signaling, cell envelope fluidity, and biofilm formation was examined. Additionally, their synergistic potential with conventional antibiotics was evaluated.
Results: RALBIs markedly attenuated the pathogenic traits of B. anthracis, including reduced macrophage association, diminished toxin secretion, and impaired sporulation. Treatment also altered growth kinetics, morphology, biofilm development and cell envelope fluidity. Importantly, the combination of RALBIs with erythromycin significantly reduced its minimum inhibitory concentration (MIC) against B. anthracis.
Conclusion: These findings highlight membrane microdomains as crucial regulators of virulence in B. anthracis and identify RALBIs as promising adjunctive agents. By targeting MMd, sterol inhibitors disrupt multiple pathogenic pathways and enhance antibiotic efficacy, underscoring their potential as novel antibacterial strategies.
期刊介绍:
Research in Microbiology is the direct descendant of the original Pasteur periodical entitled Annales de l''Institut Pasteur, created in 1887 by Emile Duclaux under the patronage of Louis Pasteur. The Editorial Committee included Chamberland, Grancher, Nocard, Roux and Straus, and the first issue began with Louis Pasteur''s "Lettre sur la Rage" which clearly defines the spirit of the journal:"You have informed me, my dear Duclaux, that you intend to start a monthly collection of articles entitled "Annales de l''Institut Pasteur". You will be rendering a service that will be appreciated by the ever increasing number of young scientists who are attracted to microbiological studies. In your Annales, our laboratory research will of course occupy a central position, but the work from outside groups that you intend to publish will be a source of competitive stimulation for all of us."That first volume included 53 articles as well as critical reviews and book reviews. From that time on, the Annales appeared regularly every month, without interruption, even during the two world wars. Although the journal has undergone many changes over the past 100 years (in the title, the format, the language) reflecting the evolution in scientific publishing, it has consistently maintained the Pasteur tradition by publishing original reports on all aspects of microbiology.