Single-domian antibody against the virulence associated with the type III secretion system of gram-negative bacteria

2017 Fiscal Year Final Research Report

• Project/Area Number: 26670791
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Sawa Teiji 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10206013)
• Co-Investigator(Kenkyū-buntansha): 天谷 文昌 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60347466) ; 中嶋 康文 関西医科大学, 医学部, 教授 (70326239)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 緑膿菌 / 細菌性肺炎 / 抗体医療 / 酸型分泌システム / PcrV / 単鎖抗体 / 遺伝子組換え

Outline of Final Research Achievements

Pseudomonas aeruginosa, a gram-negative pathogen, causes life-threatening infections. The Pseudomonal type III secretion system functions as a molecular syringe to deliver type III secretory toxins directly into the cytosol of eukaryotic cells, and also acts to inhibit innate immune mechanisms, thereby preventing bacterial clearance. Antibodies against PcrV, the cap structure in the translocational needle of the type III secretory apparatus of P. aeruginosa, block TTS toxin translocation. We investigated the therapeutic use of a recombinant anti-PcrV single-chain antibody. We synthesized a recombinant single-chain antibody, in which the heavy (VH) and light chain (VL) variable regions of the anti-PcrV monoclonal IgG are joined by a flexible peptide linker. The functions of this synthetic antibody were tested, and future potentialityl for clinical use was evaluated. Promising preliminary data about inhalational antidy therapy against bacterial pneumonia was obtained in this study.

Free Research Field

集中治療医学