2022 Fiscal Year Final Research Report
Development of rapid diagnosis of drug sensitivity and optimal choice of chemotherapeutic regimen in MAC pulmonary disease by making use of TnSeq
Project/Area Number |
21K19637
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 58:Society medicine, nursing, and related fields
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Research Institution | Niigata University |
Principal Investigator |
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Project Period (FY) |
2021-07-09 – 2023-03-31
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Keywords | 非結核性抗酸菌症 / トランスポゾン / 次世代シーケンシング |
Outline of Final Research Achievements |
For the purpose of developing the rapid diagnosis of drug sensitivity and optimal choice of chemotherapeutic regimen in MAC pulmonary disease, we have performed transposon sequencing of 7 clinical MAC strains and identified the common essential genes among the clinical strains. We identified genes of malate synthase (glcB) and type VII secretion system (eccC, eccB, eccB) as common essential genes, as well as genes of constitutive drug targets such as gyrA-gyrB, topA, embB, atpA-atpG-atpD, inhA, alr and rpoC. We have analyzed the effect of monotherapy and combination therapy for mice infected with the high virulence strain. Clarithromycin-containing chemotherapy showed the highest efficacy. We could establish the mouse model of MAC pulmonary disease for evaluating in vivo drug sensitivity.
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Free Research Field |
細菌学
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Academic Significance and Societal Importance of the Research Achievements |
肺MAC症患者由来の臨床菌株を使ったトランスポゾンシーケンシング(TnSeq)により、現行治療薬の標的以外にも肺MAC病原体の治療標的が存在することが分かりました。今回の結果は、肺MAC症の新規治療法を開拓するための薬剤標的データベースとなります。 また、感染マウスモデルを使った生体内での治療効果判定手法を確立しました。これにより、将来開発される薬剤に対する生体内治療効果判定が可能となります。
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