Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria
Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria
复制标题
人中性粒细胞α-防御素4片段化以对抗多重耐药菌
DOI：
10.3389/fmicb.2020.01147
复制
发表时间：
2020-06-03
影响因子：
5.2
通讯作者：
Jensen, Benjamin A. H.
中科院分区：
文献类型：
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作者：
Ehmann, Dirk;Koeninger, Louis;Jensen, Benjamin A. H.
多重耐药细菌的发生和传播是一个突出的健康问题。为了遏制这一紧迫的威胁，寻求新型抗菌剂的新的创新战略至关重要。在这里，我们通过胰蛋白酶消化释放了人中性粒细胞肽-4（HNP-4）的抗微生物活性。我们鉴定了具有显著抗微生物潜力的单个11个氨基酸长的片段（HNP-4（1-11）），在质量和摩尔水平上均超过全长肽。重要的是，HNP-4（1-11）对多重耐药和非耐药菌株具有同样的杀菌作用;通过N-和C-末端修饰（分别为乙酰化和酰胺化）进一步增强了这种效力。这些观察结果与不超过全长肽的细胞毒性的可忽略的细胞毒性相结合，提出了先天宿主防御肽的蛋白水解消化作为克服与耐药细菌相关的当前健康危机的新策略。
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(1-11)) with remarkable antimicrobial potential, exceeding that of the full length peptide on both mass and molar levels. Importantly, HNP-4(1-11)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.