BACTERICIDAL ACTIVITY OF HUMAN LYSOZYMES CARRYING VARIOUS LENGTHS OF POLYPROLINE CHAIN AT THE C-TERMINUS

The amphiphilic polypeptide polyproline having different chain lengths was connected to the C-terminus of human lysozyme by the recombinant DNA technique. The hydrophobicity of human lysozyme increased with inc reasing length of the polyproline chain. Although the bactericidal act ivity of wild-type lysozyme is limited to Gram-positive bacteria and t he hydrolytic activity of the mutant lysozyme decreased with increasin g chain length of polyproline, the mutant lysozymes showed bactericida l activity to Gram-negative bacteria and the activity increased with i ncreasing hydrophobicity of the mutant enzyme. Experiments with Escher ichia coli phospholipid liposomes revealed that the mutant human lysoz ymes dissipated the valinomycin-induced transmembrane electrochemical potential, and the dissipation increased with increasing hydrophobicit y. The increased hydrophobicity of the mutant enzyme may induce intera ction of lysozyme with the outer membrane and subsequent penetration i nto the inner membrane of E. coli, resulting in an increase of bacteri cidal activity. (C) 1997 Federation of European Biochemical Societies.