The adhesion of bacterial cells through extracellular matrices plays a critical role in biofilm formation. Disrupting these matrices offers a promising strategy to overcome the persistent challenge of eradicating biofilms associated with chronic infections. CsgA, a major functional amyloid within the extracellular matrix of Escherichia coli ( E. coli ), adopts a β-sheet-rich conformation that contributes to the structural integrity of biofilms. The stability of these β-sheets is maintained by an extensive hydrogen-bonding network within the protein, and their disruption can compromise biofilm viability. In this study, computational approaches were employed to identify anti-biofilm peptides capable of targeting the β-sheet structures of CsgA amyloid. Among 41 screened peptides, 10 were predicted to be toxic, and the remaining 31 were subjected to molecular docking and reactivity analyses. The HOMO–LUMO energy gap was evaluated before and after docking to assess peptide reactivity, identifying 22 peptides with high reactivity for further dynamic simulations using discrete molecular dynamics. Comparative analyses revealed that Brevinin-1BW, Kassinatuerin-3, Ranateurin-2Awa, Temporin-B, and Magainin-I-KL decreased the β-sheet content of CsgA relative to the untreated protein. Notably, Magainin-I-KL induced a 7% reduction in β-sheet content and substantial structural disruption, as evidenced by decreased hydrogen bonding, increased metastable states in the free-energy landscape, and deformation patterns in cross-correlation analysis. Steered molecular dynamics simulations further demonstrated that Magainin-I-KL exhibited greater resistance to force-induced dissociation, indicating stronger interactions with CsgA. Overall, Magainin-I-KL effectively destabilizes the CsgA amyloid structure of E. coli , suggesting its potential as a lead peptide for disrupting amyloid-based biofilm formation and enhancing antimicrobial strategies.
Vinutha et al. (Mon,) studied this question.