Amyloid unravelled: computational modelling of the TasA enzyme in stabilizing biofilms in <i>Bacillus cereus</i> and its inhibitory profiles using a drug repurposing approach

Amyloid-like proteins (ALPs) are key components of bacterial biofilms, reinforcing the extracellular matrix and supporting cell adhesion. Biofilms contribute significantly to chronic infections, antimicrobial resistance (AMR), and persistent diseases, posing major clinical and environmental challenges. TasA, a primary amyloid protein in biofilms, is well-studied in <i>Bacillus subtilis</i>, but its role in <i>Bacillus cereus</i> remains poorly understood. This study aimed to explore TasA as a target for anti-biofilm intervention. Due to the lack of an experimentally resolved structure, the 3D conformation of <i>B. cereus</i> TasA was predicted using computational modelling and validated through biophysical analyses. A structure-based virtual screening of FDA-approved compounds was conducted to identify potential inhibitors of TasA. Top candidates were further evaluated through molecular docking and triplicate molecular dynamics simulations to assess binding interactions and structural effects. Deferoxamine mesylate emerged as a strong inhibitor, demonstrating high binding affinity and destabilizing the amyloid fibril structure of TasA. This ligand-induced disruption may impair biofilm integrity and reduce AMR. Overall, the study presents TasA as a novel target for biofilm disruption in <i>B. cereus</i> and supports drug repurposing strategies for managing biofilm-associated infections.