摘要

       抗菌肽是开发新型抗菌药物的潜在分子。大肠杆菌O157:H7中Ⅰ型毒素抗毒素系统的ZorO毒素由29个氨基酸组成，其内源性表达抑制大肠杆菌生长。然而，对其抑制机制知之甚少。在这项研究中，我们证明，当ZorO在大肠杆菌细胞中表达时，位于内膜的ZorO会影响质膜的完整性和电位，从而触发细胞毒性羟基自由基的产生。我们进一步证明佐罗的五种内部氨基酸（Ala-Leu-Leu-Arg-Leu；ALLRL）对其毒性是必需的。这一结果促使我们探讨合成的ALLRL肽作为抗菌剂的潜力。在革兰氏阳性菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念珠菌中外源性添加ALLRL肽，可引起细胞膜损伤，出现生长缺陷，对革兰氏阴性菌E.coli无影响。与天然抗菌肽相比，ALLRL肽在生理盐浓度下仍保持其活性。重要的是，这种肽对哺乳动物细胞没有毒性。总之，一种有效的短肽ALLRL对革兰氏阳性菌和白色念珠菌是一种有吸引力的抗菌剂。

       Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin-antitoxin system in Escherichia coli O157:H7 is composed of 29 amino acids and its endogenous expression inhibits E. coli growth. However, little is known about its inhibitory mechanism. In this study, we demonstrate that the ZorO localized in the inner membrane affects the plasma membrane integrity and potential when expressed in E. coli cells, which triggers the production of cytotoxic hydroxyl radicals. We further show that five internal amino acids (Ala-Leu-Leu-Arg-Leu; ALLRL) of ZorO are necessary for its toxicity. This result prompted us to address the potential of the synthetic ALLRL peptide as an antimicrobial. Exogenously-added ALLRL peptide to Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a fungus, Candida albicans, trigger cell membrane damage and exhibit growth defect, while having no effect on Gram-negative bacterium, E. coli. The ALLRL peptide retains its activity under the physiological salt concentrations, which is in contrast to natural antimicrobial peptides. Importantly, this peptide has no toxicity against mammalian cells. Taken together, an effective and short peptide, ALLRL, would be an attractive antimicrobial to Gram-positive bacteria and C. albicans.

         https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669753/