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2023 Fiscal Year Final Research Report

Molecular Mechanisms of Generation of Individuality and Acquisition of Diversity in Mycobacterium tuberculosis by the Intrinsically Disordered Histone-Like Protein

Research Project

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Project/Area Number 20H03483
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionNiigata University

Principal Investigator

Matsumoto Sohkichi  新潟大学, 医歯学系, 教授 (30244073)

Co-Investigator(Kenkyū-buntansha) 白井 剛  長浜バイオ大学, バイオサイエンス学部, 教授 (00262890)
伊東 孝祐  新潟大学, 自然科学系, 准教授 (20502397)
真柳 浩太  九州大学, 薬学研究院, 講師 (50418571)
Project Period (FY) 2020-04-01 – 2024-03-31
Keywords結核 / 非結核性抗酸菌 / らい菌 / 抗酸菌 / 薬剤パーシスター / 天然変性蛋白質 / DNA凝集 / 休眠
Outline of Final Research Achievements

Mycobacterium tuberculosis, which has very low genomic plasticity, is thought to have a mechanism for obtaining diversity that is independent of DNA mutation. Since Mycobacterial DNA-binding protein 1 (MDP1), the major DNA-binding protein of mycobacteria, is an intrinsically disordered protein, we conducted a structural study of the diversity generated by its capricious behavior. We found that MDP1 has a unique activity of attaching DNA like double-sided tape. It binds and cross-links certain DNA regions at whim, independent of the base sequence, and generates a chain of DNA cross-links starting from it, randomly aggregating specific gene regions and possibly causing expression repression. This mechanism is thought to create a unique individuality in the bacterium and contribute to their acquisition of diversity as a group.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究課題は、天然変性蛋白質(IDP)による、生物の多様性の獲得機構を、初めて具体的に示したと思われる。細菌に認められる薬剤パーシスター化は、多様性による菌の生き残り戦術の好例だが、結核菌を含む抗酸菌は、特に休眠して薬剤の標的代謝を止めるためにパーシスター化しやすい。よって抗酸菌症の治療期間は半年から数年に及び、社会に大きな負担を強いている。抗酸菌の多様性の獲得や休眠誘導の重要なメカニズムを明らかにしたことは、難治性抗酸菌症の治療法開発に直結すると期待される。また癌や神経変性疾患などIDPが原因の難病も多い。IDPの機能解析が、感染症のみならず広範に、病気の制御法に結びつくことも期待される。

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Published: 2025-01-30  

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