Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria
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 tryp...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.01147/full |
| _version_ | 1811224079933374464 |
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| author | Dirk Ehmann Louis Koeninger Judith Wendler Nisar P. Malek Eduard F. Stange Jan Wehkamp Benjamin A. H. Jensen |
| author_facet | Dirk Ehmann Louis Koeninger Judith Wendler Nisar P. Malek Eduard F. Stange Jan Wehkamp Benjamin A. H. Jensen |
| author_sort | Dirk Ehmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T08:43:59Z |
| format | Article |
| id | doaj.art-7a6f5f49675a44fbbdb7d10d61f27efd |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T08:43:59Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7a6f5f49675a44fbbdb7d10d61f27efd2022-12-22T03:39:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-06-011110.3389/fmicb.2020.01147534950Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant BacteriaDirk Ehmann0Louis Koeninger1Judith Wendler2Nisar P. Malek3Eduard F. Stange4Jan Wehkamp5Benjamin A. H. Jensen6Department of Internal Medicine I, University Hospital Tübingen, Tübingen, GermanyDepartment of Internal Medicine I, University Hospital Tübingen, Tübingen, GermanyDepartment of Internal Medicine I, University Hospital Tübingen, Tübingen, GermanyDepartment of Internal Medicine I, University Hospital Tübingen, Tübingen, GermanyDepartment of Internal Medicine I, University Hospital Tübingen, Tübingen, GermanyDepartment of Internal Medicine I, University Hospital Tübingen, Tübingen, GermanyFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, Human Genomics and Metagenomics in Metabolism, University of Copenhagen, Copenhagen, DenmarkThe 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.https://www.frontiersin.org/article/10.3389/fmicb.2020.01147/fullhost defense peptidesα-defensinsproteolytic digestionmultidrug resistanceHNP-4 |
| spellingShingle | Dirk Ehmann Louis Koeninger Judith Wendler Nisar P. Malek Eduard F. Stange Jan Wehkamp Benjamin A. H. Jensen Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria Frontiers in Microbiology host defense peptides α-defensins proteolytic digestion multidrug resistance HNP-4 |
| title | Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria |
| title_full | Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria |
| title_fullStr | Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria |
| title_full_unstemmed | Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria |
| title_short | Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria |
| title_sort | fragmentation of human neutrophil α defensin 4 to combat multidrug resistant bacteria |
| topic | host defense peptides α-defensins proteolytic digestion multidrug resistance HNP-4 |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.01147/full |
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