Department of Biochemistry and Molecular Biology, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-Ku, Saitama City, Saitama 388-8570, Japan.
Department of Microbiology, School of Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan.
Toxins (Basel). 2019 Jul 4;11(7):392. doi: 10.3390/toxins11070392.
Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin-antitoxin system in O157:H7 is composed of 29 amino acids and its endogenous expression inhibits 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 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, and , and a fungus, , trigger cell membrane damage and exhibit growth defect, while having no effect on Gram-negative bacterium, . 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 .
抗菌肽是开发新型抗生素药物的潜在分子。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 生长。然而，其抑制机制知之甚少。在本研究中，我们证明了在 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自由基的产生。我们进一步表明，ZorO 的五个内部氨基酸（Ala-Leu-Leu-Arg-Leu；ALLRL）对于其毒性是必需的。这一结果促使我们研究合成 ALLRL 肽作为抗菌剂的潜力。外源性添加 ALLRL 肽到革兰氏阳性菌 和 以及真菌 中，会引发细胞膜损伤并表现出生长缺陷，而对革兰氏阴性菌 没有影响。在生理盐浓度下，该肽保留其活性，与天然抗菌肽形成对比。重要的是，这种肽对哺乳动物细胞没有毒性。总之，有效的短肽 ALLRL 可能成为革兰氏阳性菌和 的有吸引力的抗菌剂。
