A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial
A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial
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DOI：
10.3390/toxins11070392
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发表时间：
2019-07-01
期刊：
影响因子：
4.2
通讯作者：
Masuda, Michiaki
中科院分区：
文献类型：
--
作者：
Otsuka, Yuichi;Ishikawa, Tomohiro;Masuda, Michiaki
抗菌肽是一种具有潜在开发潜力的新型抗菌剂分子。大肠杆菌O 157：H7中的I型毒素-抗毒素系统的ZorO毒素由29个氨基酸组成，其内源表达抑制E.大肠杆菌生长。然而，很少有人知道它的抑制机制。在这项研究中，我们证明了定位于内膜的ZorO在E.大肠杆菌细胞，从而触发细胞毒性羟基自由基的产生。我们进一步表明，五个内部氨基酸（Ala-Leu-Leu-Arg-Leu; ALLRL）的ZorO是必要的，其毒性。这一结果促使我们解决了合成ALLRL肽作为抗菌剂的潜力。外源性ALLRL肽对革兰氏阳性菌金黄色葡萄球菌和枯草芽孢杆菌以及真菌白色念珠菌引起细胞膜损伤并表现出生长缺陷，而对革兰氏阴性菌E.杆菌ALLRL肽在生理盐浓度下保持其活性，这与天然抗菌肽相反。重要的是，这种肽对哺乳动物细胞没有毒性。总之，一个有效的短肽，ALLRL，将是一个有吸引力的抗菌革兰氏阳性菌和C。白色念珠菌
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.