The non‐enzymatic microbicidal activity of lysozymes

T4 lysozyme was thought to destroy bacteria by its muramidase activity. However, we demonstrate here that amphipathic helix stretches in the C-terminus of T4 lysozyme mediate its bactericidal and fungistatic activities. In heat-denatured T4 lysozyme, the enzymatic activity is completely abolished but unexpectedly, the antimicrobial functions remain preserved. Small synthetic peptides corresponding to amphipathic C-terminal domains of T4 lysozyme show a microbicidal activity. Its membrane disturbing activity was directly demonstrated for bacterial, fungal and plant cells but not in a hemolysis assay. Comparable results were obtained with hen egg white lysozyme. This opens up many new opportunities for optimization of lysozymes as antimicrobial agents in various applications by protein engineering.