%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-41–11) with remarkable antimicrobial potential, exceeding that of the full length peptide on both mass and molar levels. Importantly, HNP-41–11 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.