Adjuvant heavy-chain antibody drug for antibiotics

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Teikyo Heisei University
• Principal Investigator: ISHIDA Isao 帝京平成大学, 薬学部, 教授 (00415556)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 耐性菌 / ポンプ / 抗菌薬

Outline of Final Research Achievements

Heavy chain antibodies (4P94 and 4P41) which bind with the Loop1 and Loop2 of the OprM (consisting a multi-drug resistant pump) existing outside of the outer membrane, have been isolated by using the M13-phage display method, respectively. The mono, di and trimers of the Heavy chain antibodies were designed and produced in E. coli. Those antibodies were purified with Protein A, His-Trap and Endotoxin-Trap columns. When pseudomonas aeruginosa (drug sensitive PAO-1, multi-drug resistant nalB and NCGM2.S1) were treated with colistin together with those antibodies, MIC (minimum growth-inhibition concentration) of the colistin decreased to a half to one fourth of the MIC with colistin alone. The side effects for the colistin-treatment in the clinical setting were known to be kidney and neurological failures. Co-treatment of colistin with those antibodies is anticipated to reduce the side effects.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、多剤耐性菌の薬剤排出システムを抑制する一本鎖VHH抗体を補助薬に使って、病原細菌の耐性化によって使用できなくなっている抗生物質医薬品を有効な抗菌薬としてリバイバルさせようというもので、実現できれば我が国の保健医療政策に大きな経済効果を及ぼすと期待される。