Mechanism of the tropism switching of monkey malaria to human using Plasmodium knowlesi mutator line

• Project/Area Number: 25670203
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Nagasaki University
• Principal Investigator: KANEKO Osamu 長崎大学, 熱帯医学研究所, 教授 (50325370)
• Co-Investigator(Kenkyū-buntansha): KAWAI Satoru 獨協医科大学, 医学部, 准教授 (70275733)
• Research Collaborator: KATAKAI Yuko (社)予防衛生協会, 研究支援企画部感染実験支援室, 室長 ; YAHATA Kazuhide 長崎大学, 熱帯医学研究所, 助教 ; LUCKY Amuza Byarhanga 長崎大学, 医歯薬学総合研究科 ; TAKEDA Mika 長崎大学, 熱帯医学研究所, 特任研究員 ; KOCKEN Clemens オランダ霊長類医学研究センター, 主任研究員 ; DURAISINGH Manoj ハーバードTHチャン公衆衛生大学院, 教授
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 原虫 / マラリア / 人獣共通感染症 / 遺伝子導入 / 進化

Outline of Final Research Achievements

The infectivity to and pathogenicity of Plasmodium knowlesi, a causative agent of monkey malaria, in human is varied depending on the endemic areas, but the molecular basis to determine this difference is not clearly understood. Because in vitro culture-adapted P. knowlesi does not grow efficiently with human erythrocytes, I hypothesized that this growth phenotype may explain the observation in the endemic areas. To identify P. knowlesi factor(s) that enable parasites to grow with human erythrocytes, I initiated to make mutator parasite lines in which mutation rate is artificially increased by genetic manipulation. During the supported period, I established two culture-adapted P. knowlesi lines that were able to be maintained for long time with rhesus monkey erythrocytes, constructed plasmids to generate mutator lines, and developed transfection system to P. knowlesi in the laboratory. Thus, the infrastructure to generate P. knowlesi mutator lines were established.

Research Products

• [Presentation] In vitro protracted cultivation of Plasmodium knowlesi for blood stage parasitology (2015)
  • Author(s): Lucky AB, Takeda M, Yahata K, Katakai Y, Kawai S, Osamu Kaneko O.
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学三鷹キャンパス、三鷹市
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Current status of Plasmodium knowlesi culture in our laboratory. (2013)
  • Author(s): LUCKY Amuza
  • Organizer: The fourth International Symposium on Human and Monkey Malaria in Vietnam
  • Place of Presentation: 長崎大学坂本キャンパス、長崎市