Hypoxia adaptation of Mycobacterium tuberculosis based on respiratory enzymes.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16646
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Kumamoto University
• Principal Investigator: MATSUO YUICHI 熊本大学, 大学院生命科学研究部(保), 助教 (60802824)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 結核菌 / エネルギー代謝

Outline of Final Research Achievements

Dihydroorotate dehydrogenase (DHODHO) is an essential gene in Mycobacterium tuberculosis. In this study, the purification system of recombinant DHODH was edtablished. Recombinant DHODH demonstrated that dihydroorotate and quinone were utilized a substrate and an electron acceptor. On the other hand, fumarate and NADH were not used as and electro acceptor.Therefore, Mycobacterium tyberculosis DHODH was cllasified into type II DHODH. Furthoremore, Brequinar, human DHODH inhibitor, didn't inhibit mycobacterium DHODH.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

結核菌は世界3大感染症の一つであり、世界中で多くの人々が感染している。近年、既存の抗結核薬に効果が見られない、薬剤耐性菌の流行が懸念されており、新たな治療薬の開発が望まれている。本研究で得られた成果は、結核菌のジヒドロオロト酸脱水素酵素 (DHODH) の阻害剤を探索し、原子レベルでDHODHの反応機構を明らかとすることにつながる。薬剤耐性菌は公衆衛生所の危機であり、本研究は新たな薬剤開発の基盤へとつながる。