Fragment of Human Lysozyme Conjugated on the N-terminus and Displaying Antibacterial Properties

Abstract

Introduction Resistance in bacteria is becoming a dramatic problem both in community and in hospital environment and there is a great need for new antibiotics with a new mode of action. Antimicrobial peptides belong to such a class, acting by disrupting the bacterial membrane, and are promising candidates. Lysozyme is a small sized enzyme (14.4 KDa, 129 amino acids) widely distributed in living organisms and implicated in many biological processes amongst which antimicrobial activity. This activity is due to two different mechanisms: an enzymatic antimicrobial activity targeting gram positive bacteria, and an antimicrobial activity against gram positive and negative bacteria due to a domain located in the loop structure at the upper lip of the enzymatic site. This active helixloop-helix motif has been obtained by clostripain digestion of lysozyme [1]. The resulting C-terminus nonamer 1 RAWVAWRNR-NH2 is more active than the Nterminus fragment and displays a higher activity on gram positive bacteria than on gram negative bacteria [2]. Continuing previous studies using this sequence 1 and its reverse sequence 2 RNRWAVWAR-NH2 as lead structure [3], we have conjugated fatty acids on the Nterminus of these peptides. Their antibacterial activity on gram positive (S. aureus ATCC 25923) and gram negative bacteria (E. coli ATCC 25922) has been studied.