Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
Department of Biochemistry, Tzu Chi University, Hualien, Taiwan.
Sci Rep. 2017 Sep 13;7(1):11477. doi: 10.1038/s41598-017-11832-7.
The increase in the prevalence of multidrug-resistant Acinetobacter baumannii (MDRAB) strains is a serious public health concern. Antimicrobial peptides (AMPs) are a possible solution to this problem. In this study, we examined whether AMPs could be derived from phage endolysins. We synthesized four AMPs based on an amphipathic helical region in the C-terminus of endolysin LysAB2 encoded by the A. baumannii phage ΦAB2. These peptides showed potent antibacterial activity against A. baumannii (minimum inhibitory concentration, 4-64 μM), including some MDR and colistin-resistant A. baumannii. Of the four peptides, LysAB2 P3, with modifications that increased its net positive charge and decreased its hydrophobicity, showed high antibacterial activity against A. baumannii but little haemolytic and no cytotoxic activity against normal eukaryotic cells. The results of electron microscopy experiments and a fluorescein isothiocyanate staining assay indicated that this peptide killed A. baumannii through membrane permeabilization. Moreover, in a mouse intraperitoneal infection model, at 4 h after the bacterial injection, LysAB2 P3 decreased the bacterial load by 13-fold in ascites and 27-fold in blood. Additionally, LysAB2 P3 rescued sixty percent of mice heavily infected with A. baumannii from lethal bacteremia. Our results confirmed that bacteriophage endolysins are a promising resource for developing effective AMPs.
多药耐药鲍曼不动杆菌（MDRAB）菌株的流行率增加是一个严重的公共卫生问题。抗菌肽（AMPs）是解决这一问题的一种可能的方法。在这项研究中，我们研究了 AMP 是否可以从噬菌体内溶素衍生而来。我们基于编码于 A. baumannii 噬菌体 ΦAB2 的内溶素 LysAB2 的 C 末端的一个两亲性螺旋区域，合成了四个 AMP。这些肽对 A. baumannii 具有很强的抗菌活性（最小抑菌浓度，4-64 μM），包括一些 MDR 和多粘菌素耐药的 A. baumannii。在这四个肽中，LysAB2 P3 经过修饰，增加了净正电荷，降低了疏水性，对 A. baumannii 具有很高的抗菌活性，但对正常真核细胞的溶血和细胞毒性作用很小。电子显微镜实验和荧光素异硫氰酸酯染色试验的结果表明，这种肽通过破坏细胞膜来杀死 A. baumannii。此外，在小鼠腹腔感染模型中，在细菌注射后 4 小时，LysAB2 P3 使腹水和血液中的细菌负荷分别减少了 13 倍和 27 倍。此外，LysAB2 P3 使 60%感染严重的 A. baumannii 的小鼠免于致命性菌血症。我们的结果证实了噬菌体内溶素是开发有效 AMP 的有前途的资源。
