Genome-wide identification of essential genes for biofilm formation in Mycobacterium-avium intracellulare complex in order to discover novel drug targets

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Niigata University
• Principal Investigator: Tateishi Yoshitaka 新潟大学, 医歯学系, 准教授 (30433296)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: トランスポゾン / 次世代シーケンシング / 非結核性抗酸菌症

Outline of Final Research Achievements

The global incidence of the human nontuberculous mycobacteria disease is rapidly increasing. However, knowledge of gene essentiality under optimal growth conditions and conditions relevant to the natural ecology of NTM, such as hypoxia, is lacking. In this study, we utilized transposon sequencing to comprehensively identify genes essential for growth in Mycobacterium intracellulare. Of 5126 genes of M. intracellulare ATCC13950, 506 genes were identified as essential genes. The shared genes included target genes of existing antituberculous drugs. From 175 genes showing decreased fitness as conditionally essential under hypoxia, preferential carbohydrate metabolism including gluconeogenesis, glyoxylate cycle and succinate production was suggested under hypoxia. Virulence-associated genes including proteasome system and mycothiol redox system were also identified as conditionally essential under hypoxia. These findings provide critical functional genomic information for drug discovery.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

今回、主要な非結核性抗酸菌であるマイコバクテリウム・イントラセルラーエに対して、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、全ゲノム規模で生存必須遺伝子の同定を行いました。
今回同定した生存必須遺伝子群は、非結核性抗酸菌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重要な情報源となります。