Reactivation mechanism of the viable but non-culturbale (VBNC) Mycobacterium tuberculosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15442
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: 公益財団法人結核予防会 結核研究所
• Principal Investigator: Morishige Yuta 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): 2021-04-01 – 2024-03-31
• Keywords: VBNC / 結核菌 / 休眠 / LTBI

Outline of Final Research Achievements

To elucidate the molecular mechanisms of progression from latent tuberculosis infection (LTBI) to active tuberculosis, we focused on the VBNC (viable but non-culturable) state of Mycobacterium tuberculosis (Mtb), which is considered to be closely related to LTBI, and attempted to elucidate its reactivation mechanism.
In this study, we succeeded in visualizing the “on/off” of proliferation in Mtb complex by fluorescent labeling of the proteins that contribute to cell division and fluorescent amino acid incorporation, but were unable to separate and comprehensively analyze the "reactivating" and "non-reactivating" subpopulations.
However, the contribution of mycobacterial Ser/Thr kinase Pkn to the reactivation of VBNC Mtb was suggested. In addition, we demonstrated the bactericidal effect of mitoxantrone on VBNC Mtb, an anti-tumor drug which was also reported to have Pkn inhibitory activity.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

世界的に見れば、結核の脅威は今も尚続いている。潜在性結核感染症(LTBI)は、生体内で休眠(VBNC)化した結核菌の潜在感染状態と考えられる病態である。この時、菌はいわば「鳴りを潜めている」状態であり、適切な再活性化刺激によって増殖を再開するが、VBNC結核菌の詳細な再活性化機構は明らかではない。本研究において、VBNC結核菌の再活性化は結核菌Ser/Thrキナーゼの活性阻害によって抑制された。また、既存薬にVBNC結核菌を殺菌し得るものを見出した。これらの成果は、結核の発病予測や結核の再燃抑制を狙った創薬へ繋がることが期待される。