Analysis of the host cell death induced by the infection of Mycobacterium tuberculosis bacilli
Project/Area Number |
16K08346
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Environmental and hygienic pharmacy
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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)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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 / 病原性 / トランスポーター / 感染症 / サイトカイン / 細胞傷害 / 抗菌ペプチド / 微生物 / 免疫学 |
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.
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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.
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Report
(5 results)
Research Products
(39 results)
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[Journal Article] Whole-genome sequencing-based epidemiological analysis of anti-tuberculosis drug resistance genes in Japan in 2007: Application of the Genome Research for Asian Tuberculosis (GReAT) database.2019
Author(s)
Takii T, Seki K, Wakabayashi Y, Morishige Y, Sekizuka T, Yamashita A, Kato K, Uchimura K, Ohkado A, Keicho N, Mitarai S, Kuroda M, Kato S.
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Journal Title
Scientific Reports
Volume: 9(1)
Issue: 1
Pages: 12823-12823
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 5-Hydroxy-2-methylpyridine Isolated from Cigarette Smoke Condensate Aggravates Collagen-Induced Arthritis in Mice2018
Author(s)
Masafumi Takeno, Shinya Kitagawa, Junpei Yamanaka, Mayumi Teramoto, Haruka Tomita, Naohiro Shirai, Saotomo Itoh, Shigeaki Hida, Kazuichi Hayakawa, Kikuo Onozaki, Takemasa Takii
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 41
Issue: 6
Pages: 877-884
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2018-06-01
Related Report
Peer Reviewed / Open Access
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[Presentation] Comparable study between BCG Tokyo 172 type I and type II against Oxidative Stress2018
Author(s)
Keiichi Taniguchi, Yuji Miyatake, Saki Suda, Daisuke Hayashi, Shouta Ogawa, Haruka Tomita, Miki Tokuda, Saburo Yamamoto, Kikuo Onozaki, Takemasa Takii
Organizer
Keystone Symposia, Tuberculosis: Translating Scientific Findings for Clinical and Public Health Impact
Related Report
Int'l Joint Research
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[Presentation] Contribution of arginine deiminase pathway to the acid tolerance response in Mycobacterium avium substrains avium and hominissuis2018
Author(s)
Yasuhiro Horita, Saotomo Itoh, Naoya Ohara, Tetsuya Yagi, Kenji Ogawa, Shinji Maeda, Kei Nishimori, Nagatoshi Fujiwara, Yasutaka Goto, Toshio Yamazaki, Shigeaki Hida, Kikuo Onozaki, Takemasa Takii
Organizer
ASM Microbe 2018 (General Meeting of American Society for Microbiology)
Related Report
Int'l Joint Research
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[Presentation] Comparable study between BCG Tokyo 172 type I and type II against Oxidative Stress2018
Author(s)
Keiichi Taniguchi, Yuji Miyatake, Saki Suda, Daisuke Hayashi, Shouta Ogawa, Haruka Tomita, Miki Tokuda, Saburo Yamamoto, Kikuo Onozaki, Takemasa Takii
Organizer
The 52nd US-Japan Mycobacteria Panel Meeting 2018 in Niigata, Japan.
Related Report
Int'l Joint Research
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