2021 Fiscal Year Final Research Report
Analysis of mycobacterial non-coding RNA promotes the fundamental understanding for newly developing antimycobacterial therapies and strategies.
| Project/Area Number |
19K08938
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2020-2021)
Tokyo Women's Medical University (2019) |
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Principal Investigator |
Yoshida Atsushi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (40364541)
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| Co-Investigator(Kenkyū-buntansha) |
菊池 賢 東京女子医科大学, 医学部, 教授 (60214748)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 迅速発育抗酸菌 / 同定 / 薬剤感受性 / 誘導耐性 / ゲノム解析 / non-coding RNA |
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| Outline of Final Research Achievements |
More than 500 strains of rapidly growing mycobacteria (RGM) were collected from all over Japan, and the results of gene identification, drug susceptibility, and macrolide resistance mechanism were obtained. We were able to report the differences in bacterial species between specimens and isolated areas, and proposed new treatment options for M. abscessus infection.
Whole-genome analysis of isolates revealed genetic features of RGM including mobile elements, and accumulation of SNP mutations over time in 5 strains of M. abscessus subsp. abscessus, which were derived from the same patient and acquired inducible resistance to multiple drugs. By comparing these five strains, we have found RNA whose expression is increased under the administration of clarithromycin, and we are conducting a detailed analysis.
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| Free Research Field |
臨床微生物学
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| Academic Significance and Societal Importance of the Research Achievements |
多数の迅速発育抗酸菌の臨床分離株を用いた解析により、アルベカシン、シタフロキサシン、リファブチンが治療選択のオプションとなりうることを示した。さらに下気道検体では有意にM. abscessusの割合が高いこと、北日本では有意にM. abscessusの分離割合が高いことを見出した。一方ゲノム解析では、臨床分離株はしばしば外来性の因子を有すること、さらに複数の薬剤に誘導耐性を有しても、SNPの変異数はそれほど多くは増加しないことが明らかになった。転写レベルでの変化が主体であると推測されたが、関与するRNA、non-coding RNAの同定には、条件検討を含む詳細な解析が必要であった。
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