Repression of the spread of antimicrobial resistant bacteria and pathogenic bacteria using the bacterial toxin-antitoxin system

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08837
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Saitama University (2018-2020); Dokkyo Medical University (2017)
• Principal Investigator: Otsuka Yuichi 埼玉大学, 理工学研究科, 准教授 (10548861)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: トキシン－アンチトキシン系 / 細菌 / ファージ / 抗菌ペプチド / 形質導入

Outline of Final Research Achievements

The toxin-antitoxin (TA) system is a genetic module composed of a toxin and its cognate antitoxin. The ZorO toxin in Escherichia coli O157 is composed of 29 amino acids and its endogenous expression inhibits E. coli growth. Here, we demonstrated that the ZorO localized in the inner membrane affects the plasma membrane integrity. We further showed that five internal amino acids (Ala-Leu-Leu-Arg-Leu; ALLRL) of ZorO are necessary for its toxicity. Exogenously-added ALLRL peptide to Gram-positive bacteria, S. aureus and B. subtilis, and a fungus, C. albicans, trigger cell membrane damage and exhibit growth defect. 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. Furthermore, we demonstrated that the TA system suppresses the transduction which is one of the mechanisms that lead to the horizontal gene transfer.

Free Research Field

微生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

現代社会の問題である薬剤耐性菌や病原菌の蔓延は、菌の増殖に加えて、薬剤耐性遺伝子や病原遺伝子の水平伝播が要因になっている。その対策には、新規の抗菌物質や水平伝播を抑えるしくみの探索が求められる。本研究において、様々な菌に対して抗菌作用が明らかになったALLRLペプチドは新規抗菌薬の有用なシーズとして期待される。また、本研究ではTAが水平伝播の一因となる形質導入を抑えることを明確にできたので、今後TAを活性化する物質を発見できれば、薬剤耐性菌や病原菌の蔓延を抑える対策に応用できる可能性がある。