The spread of multidrug resistant bacteria owing to the intensive use of antibiotics is challenging current antibiotic therapies, and making the discovery and evaluation of new antimicrobial agents a high priority. The evaluation of novel peptide sequences of predicted antimicrobial peptides from different sources is valuable approach to identify alternative antibiotic leads. Two strategies were pursued in this study to evaluate novel antimicrobial peptides from the human β-defensin family (hBD). In the first, a 32-residue peptide was designed based on the alignment of all available hBD primary structures, while in the second a putative 35-residue peptide, hBD10, was mined from the gene DEFB110. Both hBDconsensus and hBD10 were chemically synthesized, folded and purified. They showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis, but were not hemolytic on human red blood cells. The NMR-based solution structure of hBDconsensus revealed that it adopts a classical β-defensin fold and disulfide connectivities. Even though the mass spectrum of hBD10 confirmed the formation of three disulfide bonds, it showed limited dispersion in 1 H NMR spectra and structural studies were not pursued. The evaluation of different β-defensin structures may identify new antimicrobial agents effective against multidrug-resistant bacterial strains.

中文翻译：

---

共有人β-防御素的抗菌活性和结构及其与新型推定hBD10的比较。

由于大量使用抗生素而引起的多药耐药细菌的传播对当前的抗生素疗法提出了挑战，并使发现和评估新的抗菌剂成为当务之急。评价来自不同来源的预测的抗菌肽的新肽序列是鉴定替代抗生素前导的有价值的方法。在这项研究中，采用了两种策略来评估人β-防御素家族（hBD）的新型抗菌肽。在第一个中，基于所有可用的hBD一级结构的比对设计了32个残基的肽，而在第二个中，从基因DEFB110中提取了一个推定的35个残基的肽hBD10。hBDconsensus和hBD10都是化学合成，折叠和纯化的。他们表现出对大肠杆菌的抗菌活性，金黄色葡萄球菌和结核分枝杆菌，但不能在人的红细胞上溶血。hBDconsensus的基于NMR的溶液结构表明，它具有经典的β-防御素折叠和二硫键连接性。尽管hBD10的质谱证实了三个二硫键的形成，但它在1 H NMR谱中显示出有限的分散性，因此未进行结构研究。对不同的β-防御素结构的评估可能会确定出对多药耐药细菌菌株有效的新型抗菌剂。尽管hBD10的质谱证实了三个二硫键的形成，但它在1 H NMR谱中显示出有限的分散性，因此未进行结构研究。对不同β-防御素结构的评估可能会确定出对多药耐药细菌菌株有效的新型抗菌剂。尽管hBD10的质谱证实了三个二硫键的形成，但它在1 H NMR谱中显示出有限的分散性，因此未进行结构研究。对不同β-防御素结构的评估可能会确定出对多药耐药细菌菌株有效的新型抗菌剂。