AUTHOR=Ehmann Dirk , Koeninger Louis , Wendler Judith , Malek Nisar P. , Stange Eduard F. , Wehkamp Jan , Jensen Benjamin A. H. 

TITLE=Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01147

DOI=10.3389/fmicb.2020.01147

ISSN=1664-302X

ABSTRACT=<p>The occurrence and spread of multidrug-resistant bacteria is a prominent health concern. To curb this urgent threat, new innovative strategies pursuing novel antimicrobial agents are of the utmost importance. Here, we unleashed the antimicrobial activity of human neutrophil peptide-4 (HNP-4) by tryptic digestion. We identified a single 11 amino acid long fragment (HNP-4<sub>1</sub><sub>–</sub><sub>11</sub>) with remarkable antimicrobial potential, exceeding that of the full length peptide on both mass and molar levels. Importantly, HNP-4<sub>1</sub><sub>–</sub><sub>11</sub> was equally bactericidal against multidrug-resistant and non-resistant strains; a potency that was further enhanced by N- and C-terminus modifications (acetylation and amidation, respectively). These observations, combined with negligible cytotoxicity not exceeding that of the full length peptide, presents proteolytic digestion of innate host-defense-peptides as a novel strategy to overcome the current health crisis related to antibiotic-resistant bacteria.</p>