Establishment of an experimental model system for a highly accelerated evolution using mutator malaria parasites generated by the disparity mutagenesis

2011 Fiscal Year Final Research Report

• Project/Area Number: 23659211
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Osaka University
• Principal Investigator: TANABE Kazuyuki 大阪大学, 微生物病研究所, 招へい教授 (40047410)
• Co-Investigator(Kenkyū-buntansha): HIRAI Makoto 群馬大学, 大学院・医学系, 講師 (50326849) ; HONMA Hajime 大阪大学, 微生物病研究所, 特任研究員 (10617468)
• Research Collaborator: HORII Toshihiro 大阪大学, 微生物病研究所, 教授 (80142305) ; MITA Toshihiro 東京女子医科大学, 医学部, 講師 (80318013) ; NAKAMURA Shota 大阪大学, 微生物病研究所, 助教 (90432434)
• Project Period (FY): 2011
• Keywords: マラリア / ミューテーター / Plasmodium / ゲノム / 進化 / 突然変異

Research Abstract

The present study was aimed to establish an experimental model system for predicting evolution of malaria parasites using a highly mutagenic Plasmodium berghei(mutator malaria parasite), which has defective proof reading activity of the parasite DNA polymeraseδ. Genome-wide sequence analysis of spontaneous mutations in the mutator parasite, after passages in mice over two years, revealed that mutation rate in the mutator was 75 to 100 times higher than that of control. Further, results of sulfadoxine-resistance tests suggest that the mutator system can be a novel innovative research tool, which enables us to predict drug resistance of malaria parasites.

Research Products

• [Journal Article] Age of the last common ancestor of extant Plasmodium parasite lineages (2012)
  • Author(s): Toshiyuki Hayakawa, Shin-Ichiro Tachibana, Kenji Hikosaka, Nobuko Arisue, Atsushi Matsui, Toshihiro Horii, Kazuyuki Tanabe.(7人中7番目)
  • Journal Title: Gene Volume: 502 Pages: 36-39
  • DOI: DOI:10.1016/j.gene.2012.04.037
  • Peer Reviewed
• [Journal Article] Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine-resistance gene pfcrt (2012)
  • Author(s): Nobuyuki Takahashi, Kazuyuki Tanabe, Takahiro Tsukahara, Mawuli Dzodzomenyo, Lek Dysoley, Boualam Khamlome, Jetsumon Sattabongkot, Masatoshi Nakamura, Miki Sakurai, Jun Kobayashi, Akira Kaneko, Hiroyoshi Endo, Francis Hombhanje, Takafumi Tsuboi, Toshihiro Mita.(15人中2番目)
  • Journal Title: Malar. J Volume: (in press)
  • DOI: DOI:10.1186/1475-2875-11-92
  • Peer Reviewed
• [Journal Article] The Plasmodium apicoplast genome : conserved structure and close relationship of P. ovale to rodent malaria parasites (2012)
  • Author(s): Nobuko Arisue, Tetsuo Hashimoto, Hideya Mitsui, Nirianne M. Q. Palacpac, Akira Kaneko, Satoru Kawai, Masami Hasegawa, Kazuyuki Tanabe and Toshihiro Horii(9人中8番目)
  • Journal Title: Mol. Biol. Evol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5 (2012)
  • Author(s): Kazuyuki Tanabe, Nobuko Arisue, Nirianne M. Q. Palacpac, Masanori Yagi, Takahiro Tougan, Hajime Honma, Marcelo U. Ferreira, Anna Farnert, Anders Bjorkman, Akira Kaneko, Masatoshi Nakamura, Kenji Hirayama, Toshihiro Mita, Toshihiro Horii.(14人中1, 6番目)
  • Journal Title: Vaccine Volume: 30 Pages: 1583-1593
  • DOI: 10.1016/j.vaccine.2011.12.124
  • Peer Reviewed
• [Journal Article] The origins of African Plasmodium vivax ; insights from mitochondrial genome sequencing (2011)
  • Author(s): Richard Culleton, Cevayir Coban, Fadile Yildiz Zeyrek, Pedro Cravo, Akira Kaneko, Milijaona Randrianarivelojosia, Voahangy Andrianaranjaka, Shigeyuki Kano, Anna Farnert, Ana Paula Arez, Paul M. Sharp, Richard Carter, Kazuyuki Tanabe.(13人中13番目)
  • Journal Title: PLoS One Volume: 6 Pages: e29137
  • DOI: DOI:10.1371/journal.pone.0029137
  • Peer Reviewed
• [Journal Article] Recent increase of genetic diversity in Plasmodium vivax population in the Republic of Korea (2011)
  • Author(s): Hajime Honma, Jung-Yeon Kim, Nirianne MQ Palacpac, Toshihiro Mita, Wonja Lee, Toshihiro Horii, Kazuyuki Tanabe.(7人中1, 7番目)
  • Journal Title: Malar. J Volume: 10 Pages: 257
  • DOI: DOI:10.1186/1475-2875-10-257
  • Peer Reviewed
• [Journal Article] Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations (2011)
  • Author(s): Toshihiro Mita, Meera Venkatesan, Jun Ohashi, Richard Culleton, Nobuyuki Takahashi, Takahiro Tsukahara, Mathieu Ndounga, Lek Dysoley, Hiroyoshi Endo, Francis Hombhanje, Marcelo U. Ferreira, Christopher V. Plowe, and Kazuyuki Tanabe.(13人中13番目)
  • Journal Title: J. Infect. Dis Volume: 204 Pages: 1980-1988
  • DOI: DOI:10.1093/infdis/jir664
  • Peer Reviewed
• [Journal Article] Identification of pyrimethamine-and chloroquine-resistant Plasmodium falciparum in Africa between 1984 and 1998 : genotyping of archive blood samples
  • Author(s): Yumiko Saito-Nakano, Kazuyuki Tanabe, Toshihiro Mita.(3人中2番目)
  • Journal Title: Malar. J Volume: 10
  • Peer Reviewed
• [Presentation] 高頻度突然変異発生マラリア原虫(マラリアミューテーター)のゲノムワイド変異解析と薬剤耐性研究への応用 (2012)
  • Author(s): 本間一、平井誠、中村昇太、後藤直久, 彦坂健児、美田敏宏、安永照雄、堀井俊宏、古澤満、田邉和裄(10人中1, 2, 10番目)
  • Organizer: 第81回日本寄生虫学会大会
  • Place of Presentation: 西宮
  • Year and Date: 2012-03-23
• [Presentation] Sulfadoxine/ Pyrimethamine耐性をもたらす熱帯熱マラリア原虫dhfr/ dhps遺伝子型はどのように進化していくのか (2012)
  • Author(s): 美田敏宏、大橋順、塚原高広、遠藤弘良、田邉和裄(5人中5番目)
  • Organizer: 第81回日本寄生虫学会大会
  • Place of Presentation: 西宮(兵庫県)
  • Year and Date: 2012-03-23
• [Presentation] 超加速変異型ネズミマラリア原虫の創出とその順遺伝学への応用 (2012)
  • Author(s): 平井誠、本間一、中村昇太、後藤直久、美田敏宏、鈴江和友、今井孝、松岡裕之、安永照雄、古澤満、堀井俊宏、久枝一、田邉和裄(13人中1, 2, 13番目)
  • Organizer: 第81回日本寄生虫学会大会
  • Place of Presentation: 西宮(兵庫県)
  • Year and Date: 2012-03-23
• [Presentation] The origins of African Plasmodium vivax ; Insights from mitochondrial genome sequencing (2012)
  • Author(s): Richard Cellleton, Richard Carter, 田邉和裄(3人中3番目)
  • Organizer: 第81回日本寄生虫学会大会
  • Place of Presentation: 西宮(兵庫県)
  • Year and Date: 2012-03-23
• [Presentation] パプアニューギニアにおける抗マラリア薬併用療法による熱帯熱マラリア原虫薬剤耐性遺伝子の頻度の上昇 (2011)
  • Author(s): 美田敏宏、田邉和裄(2人中2番目)
  • Organizer: 日本熱帯医学会総会
  • Place of Presentation: 東京大学
  • Year and Date: 2011-11-04
• [Presentation] Phylogenetic analysis of apicoplast genome-encoded genes reveals close affinity of the human malaria parasite, Plasmodium ovale, with rodent parasites (2011)
  • Author(s): Nobuko Arisue, Tetsuo Hashimoto, Hideya Mitsui, Akira Kaneko, Nirianne M Q, Palacpac, Masami Hasegawa, Kazuyuki Tanabe, Toshihiro Horii.(8人中7番目)
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-09
• [Presentation] 日本におけるマラリア原虫学の展開 (2011)
  • Author(s): 田邉和裄(1人中1番目)
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-17
• [Presentation] サルマラリア原虫のゲノム解読及び比較ゲノム解析による三日熱マラリア原虫特異的なゲノム変化の網羅的同定 (2011)
  • Author(s): 橘真一郎、川合覚、後藤直久、中村昇太、有末伸子、片貝祐子、本間一、パラクパックニリアン、八木正典、澤井裕美、東岸任弘、北潔、保富康宏、堀井俊宏、安永照雄、田邉和裄(16人中7, 16番目)
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-17
• [Presentation] 霊長類マラリア原虫sera遺伝子の多型解析 (2011)
  • Author(s): 有末伸子、田邉和裄、Nirianne M. Q. Palacpac、堀井俊宏(4人中2番目)
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-17
• [Presentation] Sulfadoxine耐性熱帯熱マラリア原虫の進化 (2011)
  • Author(s): 美田敏宏、大橋順、高橋延之、塚原高広、遠藤弘良、田邉和裄(6人中6番目)
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-17
• [Book] Clues to evolution of the SERA multigene family in the genus Plasmodium. In"Gene Duplicaiton" (2011)
  • Author(s): Nobuko Arisue, Nirianne M. Q. Palacpac, Kazuyuki Tanabe, Toshihiro Horii
  • Total Pages: 397
  • Publisher: InTech