Investigating inhibitory effect of sterol targeting compounds against B. anthracis: Membrane microdomain a probable target.

IF 3.4 4区 生物学 Q3 MICROBIOLOGY
Vikas Kumar Somani, Somya Aggarwal, V S Radhakrishnan, Tulika Prasad, Rakesh Bhatnagar
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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.

研究甾醇靶向化合物对炭疽芽胞杆菌的抑制作用:膜微结构域是可能的靶点。
目的:本研究旨在通过评估已知抗真菌化合物,即筏相关脂质生物合成抑制剂(RALBIs)对炭疽芽孢杆菌的病理生理作用,来评估膜微结构域(MMd)在炭疽芽孢杆菌毒力中的作用。材料和方法:fda批准的抗真菌化合物代表三种不同的类别-唑类(酮康唑),烯丙胺类(特比萘芬)和多烯类(制霉菌素),对炭疽杆菌进行了测试。这些化合物靶向参与烟雾病相关脂质生物合成的不同酶。研究了它们对孢子形成、毒素分泌、巨噬细胞相互作用、生物信号传导、包膜流动性和生物膜形成的影响。此外,还评估了它们与传统抗生素的协同潜力。结果:RALBIs显著减弱炭疽芽胞杆菌的致病特性,包括巨噬细胞关联减少、毒素分泌减少和孢子生成受损。处理还改变了生长动力学、形态、生物膜发育和细胞包膜流动性。重要的是,RALBIs与红霉素联合显著降低了其对炭疽芽孢杆菌的最低抑制浓度(MIC)。结论:这些发现强调了膜微结构域是炭疽杆菌毒力的重要调节因子,并确定了RALBIs是有希望的辅助剂。通过靶向MMd,甾醇抑制剂破坏多种致病途径并增强抗生素疗效,强调其作为新型抗菌策略的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Research in microbiology
Research in microbiology 生物-微生物学
CiteScore
4.10
自引率
3.80%
发文量
54
审稿时长
16 days
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.
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