Analysis of the host cell death induced by the infection of Mycobacterium tuberculosis bacilli

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08346
• 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: 公益財団法人結核予防会 結核研究所
• Principal Investigator: Takii Takemasa 公益財団法人結核予防会 結核研究所, 抗酸菌部, 主任研究員 (80244573)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 結核菌 / 細胞傷害活性 / Ⅶ型分泌装置 / カスパーゼ / パイロトーシス / 炎症性サイトカイン

Outline of Final Research Achievements

In this study the partial purification of cytotoxic factors was conducted from the culture filtrate of M. tuberculosis bacilli (MTB) infected human lung fibroblasts. From the mascot research using the data of LC/MS/MS analysis the several factors secreted from ESX-1, type VII secretion system encoded in RD1 region on the genome of MTB, were predicted. BCG vaccine strains, which were known to lose RD1 region, and ΔRD1 MTB showed partial cytotoxicity to human fibroblasts. These results suggested that RD1 region would be responsible to the toxicity. Next, the mechanism of the host cell death caused by MTB infection was investigated. The cytotoxicity was inhibited by caspase-1 specific inhibitor and the amount of inflammatorical cytokines in the supernatants of MTB infected cells suggested that the mechanism of the host cell death induced by MTB could be pyroptosis.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

結核菌は他の病原体のような毒素や宿主細胞に侵入するための酵素類や運動性を持たず，その病原性についての詳細は未だ不明な点が多い．本研究では研究者が見出した結核菌感染による細胞死は生菌特異的に起こること，および，病原性のない結核ワクチン(BCG)では細胞死が誘導されないことから，結核菌の病原性の解明に繋がることが期待出来る．
得られた成果は，新たなワクチンの抗原や抗結核薬の薬剤標的として医薬品開発への貢献が期待できる．