School of Life Science & Technology, Xi'an Jiaotong University, Xi'an, China.
J Pept Sci. 2012 Feb;18(2):97-104. doi: 10.1002/psc.1421. Epub 2011 Nov 14.
Emerging multidrug-resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero-immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin-resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42-60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero-immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide.
新兴的多药耐药(MDR)细菌对人类生命构成了巨大威胁,因为它们对目前可用的抗生素具有耐药性。抗菌肽的编码基因已经得到了广泛的研究,它们是对抗 MDR 细菌的新一代抗生素药物的优秀候选者。与传统抗生素不同,抗菌肽不会引起耐药性,具有无与伦比的优势。然而,由于大多数抗菌肽起源于人类以外的物种,抗菌肽的异源免疫排斥是限制其临床应用的关键劣势。在这项研究中,我们鉴定出 hGlyrichin 是一种有潜力的人类抗菌多肽。hGlyrichin 多肽可以杀死多种细菌,包括耐甲氧西林金黄色葡萄球菌、耐多药铜绿假单胞菌和耐多药结核分枝杆菌等 MDR 细菌。hGlyrichin 多肽在 42-60 位的 19 个氨基酸肽(pCM19)对于其抗菌活性至关重要。hGlyrichin 多肽通过破坏细菌膜杀死细菌。此外,与 hGlyrichin 同源的所有肽都具有抗菌活性,可以穿透细菌膜。重要的是,hGlyrichin 在体外和体内均不会引起溶血副作用。因此,基于 hGlyrichin 的优点,即不存在异源免疫排斥和溶血副作用,以及明确有效的杀灭致病 MDR 细菌,我们提出 hGlyrichin 作为一种有潜力的人类抗菌多肽。