%A Ehmann,Dirk %A Koeninger,Louis %A Wendler,Judith %A Malek,Nisar P. %A Stange,Eduard F. %A Wehkamp,Jan %A Jensen,Benjamin A. H. %D 2020 %J Frontiers in Microbiology %C %F %G English %K Host defense peptides (HDPs),α-defensins,HNP-4,Proteolytic digestion,multidrug resistant bacteria %Q %R 10.3389/fmicb.2020.01147 %W %L %M %P %7 %8 2020-June-03 %9 Original Research %# %! Peptide fragment combats MDR bacteria %* %< %T Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria %U https://www.frontiersin.org/articles/10.3389/fmicb.2020.01147 %V 11 %0 JOURNAL ARTICLE %@ 1664-302X %X 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-4111) with remarkable antimicrobial potential, exceeding that of the full length peptide on both mass and molar levels. Importantly, HNP-4111 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.