TY - JOUR
T1 - Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria
AU - Ehmann, Dirk
AU - Koeninger, Louis
AU - Wendler, Judith
AU - Malek, Nisar P.
AU - Stange, Eduard F.
AU - Wehkamp, Jan
AU - Jensen, Benjamin A.H.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - HNP-4
KW - host defense peptides
KW - multidrug resistance
KW - proteolytic digestion
KW - α-defensins
U2 - 10.3389/fmicb.2020.01147
DO - 10.3389/fmicb.2020.01147
M3 - Journal article
C2 - 32582092
AN - SCOPUS:85086587633
SN - 1664-302X
VL - 11
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 1147
ER -