Functional analysis and characterization of KatG mutations associated with isoniazid-resistant Mycobacterium tuberculosis and their crystal structures

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15695
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KIM HYUN 国立感染症研究所, 細菌第二部, 主任研究官 (90648817)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: M.tuberculosis KatG / Isoniazid-resistance

Outline of Final Research Achievements

As isoniazid (INH) is an integral first-line anti-tuberculosis drug, INH-resistant Mycobacterium tuberculosis has become an urgent global health problem. Mutations of several genes, such as katG, inhA, and ahpC in M. tuberculosis have been reported to be associated with INH-resistance. However, all specific mutation points involved in the resistance have not yet been determined.
In this study, we sequenced the whole genomes of 11 INH-resistant M. tuberculosis clinical isolates collected from Taiwan and found five novel mutants in the katG. KatG exhibits catalase and peroxidase activities and also activates INH. Therefore, it seems that these novel mutations in the katG are involved in INH-resistance. This study aimed to elucidate the interaction between novel mutants in the katG and INH-resistance.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究課題は積極的に国内外の学術研究会において発表するとともに、論文著書として広く公開する。ホームページや報道機関の発表、市民公開講座等を通じて、研究成果を一般国民に向けて分かりやすく発信することも予定している。また、研究成果のうち必要なものについては特許の申請を行い、他の研究者や研究機関において利用可能な状態にする。