The increase of antimicrobial resistance in microorganisms is currently one of the biggest public health challenges, with immense financial burdens for health systems and a projected 10 million deaths per year by 2050. Therefore, the world is in urgent need of alternatives to currently used antibiotic drugs. The antimicrobial enzyme lysozyme has broad-spectrum antimicrobial activity in aggregated forms and is therefore an interesting candidate. Here, amyloid-like worm-shaped aggregates (worms) of hen egg white lysozyme (HEWL) were made using a reductive pathway and compared to amyloid fibrils produced by acid hydrolysis. The strongly pH-dependent aggregation of HEWL into worms induces a transition of secondary structure from α-helices to β-sheets. The colloidal stability of the worms enabled direct comparisons of minimum inhibitory concentrations, which were lower for both HEWL worms and amyloid fibrils than that for native HEWL against the Gram-positive Staphylococcus aureus. Furthermore, the antimicrobial activity of the HEWL aggregates was broadened to the Gram-negative Escherichia coli, and the fungus Candida albicans. This non-enzymatic antimicrobial effect can be attributed to the interaction of the accumulated positive charges in the amyloid fibrils with negatively charged cell walls and membranes leading to their disruption and ultimately cell lysis. The structural and functional investigations of HEWL and its aggregates presented here are crucial for the understanding of the charge-mediated antimicrobial performance and open up new possibilities to create broad-spectrum antimicrobial materials for a wide range of applications.

Self-assembly of lysozyme aggregates with enhanced antimicrobial activity

ACS Spring 2022

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