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

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.

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.

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.

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.