Comprehensive elucidation of fitness cost in drug-resistant malaria parasites through while life cycle

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Juntendo University
• Principal Investigator: Tachibana Shin-Ichiro 順天堂大学, 医学部, 助教 (90414630)
• Co-Investigator(Kenkyū-buntansha): 平井 誠 順天堂大学, 医学部, 准教授 (50326849)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: マラリア原虫 / 薬剤耐性 / 適応度 / 種内競争

Outline of Final Research Achievements

Acquisition of drug resistance with gene mutations generally raises decrease of fitness in organisms, and therefore, the drug resistance may be disadvantageous under conditions without the drug. To assess fitness costs imposed by resistant to sulfadoxine (SX) alone, we comprehensively evaluated parasite fitness within-hosts and within-vectors using a transgenic rodent malaria parasite Plasmodium berghei. Competitive experiments in which SX-resistant and wild-type parasites were co-infected into mice showed a similar growth rate. In contrast, growth rate was significantly greater in SX-resistant clones than that in wild-type clones within vectors. These observations suggest that acquisition of SX resistance did not alter the within-rodent fitness in the absence of the drug, whereas it unexpectedly provoked a fitness advantage within mosquitos.

Free Research Field

寄生虫学

Academic Significance and Societal Importance of the Research Achievements

一般的に、遺伝子変異によって薬剤耐性を獲得した病原体には、適応度の低下が見られる。しかしながら本研究によって、マラリア原虫では薬剤耐性の獲得が適応度の低下を引き起こさない事例があるという、これまでの常識を覆す知見が得られた。本研究成果は、今後も抗マラリア薬を持続的かつ効果的に利用するための方策を考える上で参照されるべきものであり、国際保健に貢献するものである。