Expanding functional genomics of nontuberculous mycobacteria for establishing strategies for prevention, predictive diagnosis and drug development

2022 Fiscal Year Final Research Report

• Project/Area Number: 20KK0216
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Niigata University
• Principal Investigator: Yoshitaka Tateishi 新潟大学, 医歯学系, 准教授 (30433296)
• Co-Investigator(Kenkyū-buntansha): 港 雄介 藤田医科大学, 医学部, 講師 (10836620) ; 森重 雄太 公益財団法人結核予防会 結核研究所, 抗酸菌部 結核菌情報科, 研究員 (40765608)
• Project Period (FY): 2020-10-27 – 2023-03-31
• Keywords: 非結核性抗酸菌 / 肺MAC症 / 病原因子 / 代謝パスウェイ解析

Outline of Final Research Achievements

In this study, we have performed TnSeq of 8 Mycobacterium itracellulare clinical strains and compared the gene essentiality between clinical strains and the type strain ATCC13950. Gene essentiality was increased in the genes of gluconeogenesis, type VII secretion system and cysteine desulfrase. The bacterial growth was inhibited by suppressing the expression of these genes. The genes required for mouse infection in clinical strains partially shared the genes required for hypoxic pellicle formation in ATCC13950. These findings provide functional genomic information for drug discovery and novel insight into the favorable adaptation to hypoxia in clinical strains.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

今回、非結核性抗酸菌マイコバクテリウム・イントラセルラーエについて、ゲノム型の異なる患者由来臨床菌株に対して、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、複数の臨床菌株に共通した薬剤標的となる遺伝子群の同定を行いました。今回同定した遺伝子群は、非結核性抗酸菌臨床菌株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貴重な情報源となります。