Clarification of host adaptation mechanisms by using mutator malaria parasite

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K07095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Juntendo University
• Principal Investigator: Hirai Makoto 順天堂大学, 医学部, 准教授 (50326849)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: マラリア

Outline of Final Research Achievements

This study addressed this issue by utilizing a mutator strain of rodent malaria parasite.Initially, we attempted to identify the genetic factors that determine fitness in vertebrates (mice), particularly those under drug selection pressure. As a result, we identified novel mutations in drug resistance-conferring genes, and notably, successfully identified novel mutations in genes associated with resistance stabilization (resistance stabilization gene mutations). When drug resistance-conferring gene mutations were introduced into wild-type parasites, they exhibited weak resistance. However, upon further introduction of resistance stabilization gene mutations, resistance levels increased. Conversely, when only resistance stabilization gene mutations were introduced into wild-type parasites, no resistance was observed.

Free Research Field

マラリア学

Academic Significance and Societal Importance of the Research Achievements

本研究により、マラリア原虫に薬剤耐性を付与する突然変異遺伝子変異を同定し、さらに耐性の安定化にかかわる新規遺伝子変異（耐性安定化遺伝子変異）の特定に成功した。本研究成果は、耐性安定化遺伝子変異が耐性付与遺伝子変異に作用することで、耐性の上昇と安定化にかかわるものと結論した。これらの結果は、現在問題となるマラリア薬剤耐性を解決するための重要な基礎データであり、耐性原虫の撲滅に寄与する大変重要な知見である。