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A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial

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
Author to whom correspondence should be addressed.
Toxins 2019, 11(7), 392;
Received: 6 June 2019 / Revised: 28 June 2019 / Accepted: 30 June 2019 / Published: 4 July 2019
(This article belongs to the Special Issue Toxin-antitoxin (TA) systems)
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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. View Full-Text
Keywords: Toxin–Antitoxin system; ZorO; antimicrobial peptide Toxin–Antitoxin system; ZorO; antimicrobial peptide

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Otsuka, Y.; Ishikawa, T.; Takahashi, C.; Masuda, M. A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial. Toxins 2019, 11, 392.

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