Role of babesiacidal proteins in the vector tick and development of therapeutic agents against bebesiosis

2012 Fiscal Year Final Research Report

• Project/Area Number: 21380190
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: National Agriculture and Food Research Organization
• Principal Investigator: TSUJI Naotoshi 独立行政法人農業・食品産業技術総合研究機構, 動物衛生研究所・細菌・寄生虫研究領域, 主任研究員 (70355171)
• Co-Investigator(Kenkyū-buntansha): FUJISAKI Kozo 国立大学法人鹿児島大学, 農学部, 教授 (00292095)
• Co-Investigator(Renkei-kenkyūsha): HATTA Takeshi 独立行政法人農業・食品産業技術総合研究機構, 動物衛生研究所・細菌・寄生虫研究領域, 研究員 (00455304)
• Project Period (FY): 2009 – 2012
• Keywords: 獣医学 / 感染症 / 吸血性節足動物 / マダニ / バベシア症

Research Abstract

Several babesiacidal proteins associated with differentiation and proliferation of Babesia parasites were identified from the piroplamosis vector tick, Haemaphysalis longicornis. Peptides based on the secondary structure possessed lethal effect on the intra-erythrocytic stage of Babesia that cause animal babesiosis. Lethal-effects of these peptides were also detected against other animal protozoan disease including toxoplasmosis.

Research Products

• [Journal Article] HlCPL-A, a cathepsin L-like cysteine protease from the ixodid tick Haemaphysalis longicornis, modulated midgut proteolytic enzymes and their inhibitors during blood meal digestion (2013)
  • Author(s): Yamaji K, Miyoshi T, Hatta T, MatsubayashiM, Alim MA, Anisuzzaman, KushibikiS, Fujisaki K, Tsuji N.
  • Journal Title: Infect Genet Evol Volume: 16C Pages: 206-11
  • DOI: DoI:10.1016/j.meegid.2013.01.018.
• [Journal Article] A hemocyte-derivedKunitz-BPTI-type chymotrypsin inhibitor, HlChI, from the ixodid tick Haemaphysalis longicornis, plays regulatory functions in tick blood-feeding processes (2012)
  • Author(s): Alim MA, Miyoshi T, Islam MK, Hatta T, Yamaji K, Matsubayashi M, Fujisaki K. Tsuji N.
  • Journal Title: Insect Biochem Mol Biol Volume: 42 Pages: 925-34
  • DOI: doi:10.1016/j.ibmb.2012.09.005.
• [Journal Article] Semi-artificial mouse skin membrane feeding technique for adult tick, Haemaphysalis longicornis (2012)
  • Author(s): Hatta T, Miyoshi T, Matsubayashi M, IslamMK, Alim MA, Uzzaman A, YamajiK, Fujisaki K, Tsuji N.
  • Journal Title: Parasit Vectors Volume: 15 Pages: 263
  • DOI: DOI:10.1186/1756-3305-5-263.
• [Journal Article] Quantitative PCR-based parasite burden estimation of Babesia gibsoni in the vector tick, Haemaphysalis longicornis (Acari: Ixodidae), fed on an experimentally pre-infected dog (2012)
  • Author(s): Hatta T, Matsubayashi M, Miyoshi T, IslamMK, Alim MA, Anisuzzaman, YamajiK, Fujisaki K, Tsuji N.
  • Journal Title: J Vet Med Sci Volume: 75 Pages: 1-6
  • URL: https://www.jstage.jst.go.jp/article/jvms/75/1/75_12-0175/_article
• [Journal Article] HlSRB, a Class B scavenger receptor,is key to the granulocyte-mediated microbial phagocytosis in ticks (2012)
  • Author(s): Aung KM, Boldbaatar D, Umemiya-Shirafuji R, Liao M, Tsuji N, Xuenan X, Suzuki H, Kume A, Galay RL, Tanaka T, Fujisaki K.
  • Journal Title: PLoS One Volume: 7 Pages: e33504
  • DOI: DOI:10.1371/journal.pone.0033504
• [Journal Article] Tick longicin implicated in the arthropod transmission of Toxoplasma gondii (2012)
  • Author(s): Tanaka T, Maeda H, Galay RL, Boldbattar D, Umemiya-Shirafuji R, Suzuki H, XuanX, Tsuji N. Fujisaki K.
  • Journal Title: J Veterinar Sci Technolo Volume: 3 Pages: e112
  • URL: http://dx.doi.org/10.4172/2157-7579.1000112
• [Journal Article] Anti-babesial activity of a potent peptide fragment derived from longicin of Haemaphysalis longicornis (2012)
  • Author(s): Galay RL, Maeda H, Aung KM, Umemiya-Shirafuji R, Xuan X, IgarashiI, Tsuji N, Tanaka T, Fujisaki K.
  • Journal Title: Trop Anim Health Prod Volume: 44 Pages: 343-348
  • DOI: DOI:10.1007/s11250-011-0027-7
• [Journal Article] Parasiticidal activity of Haemaphysalis longicornis longicin P4 peptide against Toxoplasma gondii (2012)
  • Author(s): Tanaka T, Maeda H, Matsuo T, Boldbattar D, Umemiya-Shirafuji R, Kume A, Suzuki H, Xuan X, Tsuji N, Fujisaki K.
  • Journal Title: Peptides Volume: 34 Pages: 242-250
  • DOI: DOI:10.1016/j.peptides.2011.07.027.
• [Journal Article] Longistatin is an unconventional serine protease and induces protective immunity against tick infestation (2011)
  • Author(s): Anisuzzaman, Islam MK, Alim MA. Alim, Miyoshi T, Hatta T, Yamaji K, Matsumoto Y, Fujisaki K, Tsuji N.
  • Journal Title: Mol Biochem Parasitol Volume: 182 Pages: 45-53
  • DOI: DOI:10.1016/j.molbiopara.2011.12.002
• [Journal Article] Longistatin, a novel plasminogen activator from vector ticks, is resistant to plasminogen activator inhibitor-1 (2011)
  • Author(s): Anisuzzaman, Islam MK, Alim MA, MiyoshiT, Hatta T, Yamaji K, MatsumotoY, Fujisaki K, Tsuji N.
  • Journal Title: Biochem Biophys Res Commun Volume: 413 Pages: 599-604
  • DOI: DOI:10.1016/j.bbrc.2011.09.009
• [Journal Article] Longistatin, a plasminogen activator, is key to the availability of blood-meals for ixodid ticks (2011)
  • Author(s): Anisuzzaman, Islam MK, Alim MA, MiyoshiT, Hatta T, Yamaji K, Matsumoto Y, Fujisaki K, Tsuji N.
  • Journal Title: PLoS Pathog Volume: 7 Pages: e1001312
  • DOI: DOI:10.1371/journal.ppat.1001312
• [Journal Article] Hlcyst-1 and Hlcyst-2 are potential inhibitors ofHlCPL-A in the midgut of the ixodid tickHaemaphysalis longicornis (2010)
  • Author(s): Yamaji K, Tsuji N, Miyoshi T, IslamMK, Hatta T, Alim MA, Anisuzzaman, Kushibiki S, Fujisaki K.
  • Journal Title: J Vet Med Sci Volume: 72 Pages: 599-604
  • URL: https://www.jstage.jst.go.jp/article/jvms/72/5/72_09-0561/_article
• [Journal Article] Leucine aminopeptidase, HlLAP, from the ixodid tick Haemaphysalis longicornis, plays vital roles in the development of oocytes (2010)
  • Author(s): Hatta T, Tsuji N, Miyoshi T, Islam MK, Alim MA, Yamaji K, Anisuzzaman, Fujisaki K.
  • Journal Title: Parasitol Int Volume: 59 Pages: 286-289
  • DOI: DOI:10.1016/j.parint.2010.03.001.
• [Journal Article] Longistatin, anovel EF-hand protein from the ixodid tick Haemaphysalis longicornis, is a potent plasminogen activator and is required for anticoagulation of host blood-meals (2010)
  • Author(s): Anisuzzaman, M. Islam MK, Miyoshi T, AlimMA, Hatta T, Yamaji K, MatsumotoY, Fujisaki K, Tsuji N.
  • Journal Title: Int J Parasitol Volume: 40 Pages: 721-729
  • DOI: DOI:10.1016/j.ijpara.2009.11.004.
• [Journal Article] AKunitz-type trypsin inhibitor from the midgut of the ixodid tick and its endogenous target serine proteinase (2010)
  • Author(s): Miyoshi T, Tsuji N, Islam MK, Alim MA, Hatta T, Yamaji K, Anisuzzaman, Fujisaki K.
  • Journal Title: Mol Biochem Parasitol Volume: 170 Pages: 112-115
  • DOI: DOI:10.1016/j.molbiopara.2009.12.005.
• [Journal Article] Structural characterization and cytolytic activity of a potent antimicrobial motif in longicin, a defensin-like peptide in the tick Haemaphysalis longicornis (2010)
  • Author(s): Rahman M, Tsuji N, Boldbaatar D, Battur B, Liao M, Umemiya-Shirafuji R, You M, Tanaka T, Fujisaki K.
  • Journal Title: J Vet Med Sci Volume: 72 Pages: 149-156
  • URL: https://www.jstage.jst.go.jp/article/jvms/72/2/72_09-0167/_article
• [Journal Article] A salivary cystatin, HlSC-1, from the ixodid tick Haemaphysalis longicornis play roles in the blood feeding processes (2009)
  • Author(s): Yamaji K, Tsuji N, Miyoshi T, Islam MK, Hatta T, Alim MA, Anisuzzaman, Kushibiki S, Fujisaki K.
  • Journal Title: Parasitol Res Volume: 106 Pages: 61-68
  • DOI: DOI:10.1007/s00436-009-1626-3.
• [Journal Article] The Kunitz-like modulatory protein, Haemangin, is vital for hard tick blood feeding success (2009)
  • Author(s): Islam MK, Tsuji N, Miyoshi T, Alim MA, Huang X, Hatta T, Fujisaki K.
  • Journal Title: PLoS Pathog Volume: 5 Pages: e1000497
  • DOI: DOI:doi:10.1371/journal.ppat.1000497.
• [Journal Article] Hemoglobinase activity of a cysteine protease from the ixodid tick Haemaphysalis longicornis (2009)
  • Author(s): Yamaji K, Tsuji N, Miyoshi T, Islam MK, Hatta T, Alim MA, Anisuzzaman, Takenaka A, Fujisaki K.
  • Journal Title: Parasitol Int Volume: 58 Pages: 232-237
  • DOI: DOI:10.1016/j.parint.2009.05.003.
• [Journal Article] Leucine aminopeptidase in the ixodid tick Haemaphysalis longicornis: endogenous expression profiles in midgut (2009)
  • Author(s): Hatta T, Tsuji N, Miyoshi T, Alim MA, Islam MK, Fujisaki K.
  • Journal Title: J Vet Med Sci Volume: 71 Pages: 589-594
  • URL: https://www.jstage.jst.go.jp/article/jvms/71/5/71_5_589/_article
• [Presentation] マダニロンギスタチンのRAGE吸着を介した宿主炎症反応の抑制 (2013)
  • Author(s): アニスザマン,三好猛晴,八田岳士,松林誠,イスラムカイルル,アリムアブドゥル,藤崎幸蔵,辻尚利
  • Organizer: 東京医科歯科大学湯島キャンパス
  • Place of Presentation: 文京区
  • Year and Date: 2013-03-29
• [Presentation] フタトゲチマダニロンギシンにおける抗バベシア活性を持つペプチド部位の検索 (2013)
  • Author(s): 田仲哲也,Remil Linggatong Galay,前田大輝,Aung Kyaw Min,白藤(梅宮)梨可,玄学南,五十嵐郁男,望月雅美,辻尚利,藤崎幸蔵
  • Organizer: 東京大学駒場キャンパス
  • Place of Presentation: 渋谷区
  • Year and Date: 2013-03-28
• [Presentation] 人工吸血法により作出したバベシア原虫感染マダニの中腸mRNA-seq解析 (2012)
  • Author(s): 八田岳士,三好猛晴,松林誠,アニスザマン,アリムアブドゥル,山地佳代子,五十嵐郁男,藤崎幸蔵,辻尚利
  • Organizer: 第10回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 群馬大学(前橋市)
  • Year and Date: 2012-10-12
• [Presentation] フタトゲチマダニ人工吸血系の確立とBabesia ovata感染マダニ作出への応用 (2012)
  • Author(s): 八田岳士,三好猛晴,松林誠,アニスザマン,アリムアブドゥル,山地佳代子,五十嵐郁男,藤崎幸蔵,辻尚利
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
  • Year and Date: 2012-09-14
• [Presentation] Longistatin, a plasminogen activator from the tick Haemaphysalis longicornis, binds with RAGE and induces protective immunity (2012)
  • Author(s): アニスザマン,アリムアブドゥル,イスラムカイルル,三好猛晴,八田岳士,松林 誠,藤崎幸 蔵,辻尚利
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
  • Year and Date: 2012-09-14
• [Presentation] ワクチンの科学:課題と試み.寄生虫ワクチン分子の探索-マダニの吸血・病原体伝搬調節物質 (2011)
  • Author(s): 辻尚利
  • Organizer: 第32回東京大学獣医学・応用動物科学セミナー
  • Place of Presentation: 東京大学(文京区)
  • Year and Date: 2011-11-21
• [Presentation] HlChI, a blood induced Kunitz-like protein from the hemocytes of the ixodid tick Haemaphysalis longicornis, is a potent chymotrypsin inhibitor (2011)
  • Author(s): アニスザマン,Khyrul Islam,Abdul Alim,三好猛晴,八田岳士,山地佳代子,松林 誠, 松本安喜,藤崎幸蔵,辻尚利
  • Organizer: 第152日本獣医学会学術集会
  • Place of Presentation: 大阪府立大学(堺市)
  • Year and Date: 2011-09-21
• [Presentation] Longistatin, a plasminogen activator from the salivary-gland of ixodid tick with two EF-hand domains, functions like a serine protease (2011)
  • Author(s): Anisuzzaman, Islam Mkhyrul, Miyoshi Takeharu, Abdul M Alim, Hatta Takeshi, Yamaji Kayoko, MatsumotoYasunobu, Fujisaki Kozo, Tsuji Naotoshi
  • Organizer: 第80日本寄生虫学会大会
  • Place of Presentation: 慈恵医科大学(港区)
  • Year and Date: 2011-07-17
• [Presentation] マダニ中腸由来セリンプロテアーゼインヒビターのバベシア原虫増殖抑制効果 (2011)
  • Author(s): 三好猛晴,八田岳士,M.Abdul Alim,Anisuzzaman,山地佳代子,佐藤真澄,藤崎幸蔵,辻尚利
  • Organizer: 第80日本寄生虫学会大会
  • Place of Presentation: 慈恵医科大学(港区)
  • Year and Date: 2011-07-17
• [Presentation] A novel chymotripsin inhibitor from the hard tick Haemaphysalis longicornis is involved in blood-feeding process (2011)
  • Author(s): M. Abdul Alim, Naotoshi Tsuji, Takeharu Miyoshi, M. Khyrul Islam, Takeshi Hatta, Kayoko Yamaji, Anisuzzaman, Kozo Fujisaki
  • Organizer: 第80日本寄生虫学会大会
  • Place of Presentation: 慈恵医科大学(港区)
  • Year and Date: 2011-07-17
• [Presentation] わが国の寄生虫病の現状と研究展開-マダニから学ぶマダニ媒介感染症の手がかり (2011)
  • Author(s): 辻尚利
  • Organizer: 平成22年度日本獣医師会獣医学術集会年次大会
  • Place of Presentation: 長良川国際会議場(岐阜市)
  • Year and Date: 2011-02-11
• [Presentation] Longistatin plays vital roles in blood pool formation and successful feeding by ixodid tick (2010)
  • Author(s): Anisuzzaman, Islam M Khyrul, Miyoshi Takeharu, Abdul M Alim, Hatta Takeshi, Yamaji Kayoko, MatsumotoYasunobu, Fujisaki Kozo, Tsuji Naotoshi
  • Organizer: Haemaphysalis longicornis The XIIth International Congress of Parasitology
  • Place of Presentation: 日旭川市大雪クリスタルホール(旭川市)
  • Year and Date: 2010-05-21
• [Presentation] フタトゲチマダニ中腸由来 Kunitz type プロテアーゼインヒビターによ るマダニ内在性セリンプロテアーゼ活性の 制御 (2010)
  • Author(s): 三好猛晴,辻尚利,八田岳士, M. Khyrul Islam, M.Abdul Alim, Anisuzzaman、山地佳 代子,藤崎幸蔵
  • Organizer: 第79日本寄生虫学会大会
  • Place of Presentation: 川市大雪クリスタルホール(旭川 市)
  • Year and Date: 2010-05-21
• [Presentation] バベシア原虫のマダニ介卵伝播におけるマダニアミノペプチダーゼの役割 (2009)
  • Author(s): 八田岳士,辻尚利,三好猛晴,山地佳代子,Anisuzzaman,藤崎幸藏
  • Organizer: 第8回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 千里ライフサイエンスセンターサイエンスホール(大阪市)
  • Year and Date: 2009-10-09
• [Presentation] マダニ中腸由来Kunitz typeセリ ンプロテアーゼインヒビターによる内在性プ ロテアーゼ活性の制御 (2009)
  • Author(s): 三好猛晴,辻尚利,Khyrul Islam,八田岳 士,Abdul Alim,山地佳代子,Anisuzzaman, 藤崎幸藏
  • Organizer: 第148回日本獣 医学会学術集会
  • Place of Presentation: と りぎん文化会館(鳥取市)
  • Year and Date: 2009-09-26
• [Presentation] マ ダニカテプシンL様システインプロテアーゼ の性状解析 (2009)
  • Author(s): 山地佳代子,辻尚利,三好猛晴,八田岳士,Abdul Alim,Anisuzzaman,藤崎幸藏
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: とりぎん文化 会館(鳥取市)
  • Year and Date: 2009-09-26
• [Presentation] Longistatin, anEF-hand protein, plays vital roles in the acquisition of blood-meals by ticks (2009)
  • Author(s): Anisuzzaman,三好猛晴,Khyrul Islam,八田 岳士,Abdul Alim,山地佳代子,松本安喜,藤崎幸藏,辻尚利
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: とりぎん文化会館(鳥取市)
  • Year and Date: 2009-09-26
• [Presentation] アミノペプチダーゼHlLAP遺伝子発現抑制マダニにおける産卵数減少メカニズムの解析 (2009)
  • Author(s): 八田岳士,辻尚利,三好猛晴,Abdul Alim,山地佳代子,Anisuzzaman,藤崎幸藏
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: とりぎん文化会館(鳥取市)
  • Year and Date: 2009-09-26
• [Presentation] マダニの病原体伝搬ネットワーク:バベシア原虫伝搬におけるヘモグロビン分解経路の役割 (2009)
  • Author(s): 辻尚利
  • Organizer: 第20回日本生体防御学会学術集会
  • Place of Presentation: 東京医科歯科大学(文京区)
  • Year and Date: 2009-07-26
• [Presentation] バベシア原虫感染フタトゲチマダニ栃木県総合文化センター.栃木県における卵巣内移行原虫の定量的検出 (2009)
  • Author(s): 八田岳士,辻尚利,三好猛晴,Abdul Alim,山地佳代子,Anisuzzaman,藤崎幸藏
  • Organizer: 第147回日本獣医学会学術集
  • Place of Presentation: 栃木県総合文化センター(宇都宮市)
  • Year and Date: 2009-04-03
• [Book] マダニの生存戦略と病原体伝播 (2012)
  • Author(s): 辻尚利,藤崎幸蔵
  • Total Pages: 50,119-126
  • Publisher: 化学と生物
• [Book] マダニの吸血調節物質 (2011)
  • Author(s): 辻尚利
  • Total Pages: 4,263-267
  • Publisher: 日本獣医師会雑誌
• [Remarks]
  • URL: http://www.niah.affrc.go.jp/collab/person/tsuji/index.html