Genome-wide identification of essential genes for biofilm formation in Mycobacterium-avium intracellulare complex in order to discover novel drug targets
| Project/Area Number |
18K08172
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53030:Respiratory medicine-related
|
|---|
| Research Institution | Niigata University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | トランスポゾン / 次世代シーケンシング / 非結核性抗酸菌症 / 非結核性抗酸菌 / バイオフィルム / オミクッス解析 |
|---|
| Outline of Final Research Achievements |
The global incidence of the human nontuberculous mycobacteria disease is rapidly increasing. However, knowledge of gene essentiality under optimal growth conditions and conditions relevant to the natural ecology of NTM, such as hypoxia, is lacking. In this study, we utilized transposon sequencing to comprehensively identify genes essential for growth in Mycobacterium intracellulare. Of 5126 genes of M. intracellulare ATCC13950, 506 genes were identified as essential genes. The shared genes included target genes of existing antituberculous drugs. From 175 genes showing decreased fitness as conditionally essential under hypoxia, preferential carbohydrate metabolism including gluconeogenesis, glyoxylate cycle and succinate production was suggested under hypoxia. Virulence-associated genes including proteasome system and mycothiol redox system were also identified as conditionally essential under hypoxia. These findings provide critical functional genomic information for drug discovery.
|
| Academic Significance and Societal Importance of the Research Achievements |
今回、主要な非結核性抗酸菌であるマイコバクテリウム・イントラセルラーエに対して、トランスポゾン（動く遺伝子）による変異株ライブラリーの作成と次世代シーケンサーによる全ゲノムシーケンシングを組み合わせたトランスポゾンシーケンシングを行い、全ゲノム規模で生存必須遺伝子の同定を行いました。
今回同定した生存必須遺伝子群は、非結核性抗酸菌の薬剤標的となるため、肺MAC症に対する新しい治療薬の開発において重要な情報源となります。
|
Report
(4 results)
Research Products
(16 results)
-
-
-
[Journal Article] Structure-Activity Relationships of Pyrazolo[1,5-a]pyrimidin-7(4H)-ones as Antitubercular Agents.2021
Author(s)
Oh S, Libardo MDJ, Azeeza S, Pauly GT, Roma JSO, Sajid A, Tateishi Y, Duncombe C, Goodwin M, Ioerger TR, Wyatt PG, Ray PC, Gray DW, Boshoff HIM, Barry CE 3rd.
-
Journal Title
ACS Infect Dis.
Volume: 7
Issue: 2
Pages: 479-492
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Higher genome mutation rates of Beijing lineage of Mycobacterium tuberculosis during human infection2020
Author(s)
Hakamata M, Takihara H, Iwamoto T, Tamaru A, Hashimoto A, Tanaka T, Kaboso SA, Gebretsadik G, Ilinov A, Yokoyama A, Ozeki Y, Nishiyama A, Tateishi Y, Moro H, Kikuchi T, Okuda S, Matsumoto S.
-
Journal Title
Sci Rep
Volume: 10
Issue: 1
Pages: 17997-17997
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Characteristic profile of antibody responses to PPD, ESAT-6, and CFP-10 of Mycobacterium tuberculosis in pulmonary tuberculosis suspected cases in Surabaya, Indonesia.2019
Author(s)
Dewi DNSS, Mertaniasih NM, Soedarsono, Ozeki Y, Artama WT, Fihiruddin, Niki M, Tateishi Y, Ato M, Matsumoto S.
-
Journal Title
Braz J Infect Dis
Volume: 23
Issue: 4
Pages: 246-253
DOI
Related Report
-
-
-
-
-
-
-
-
-
-
