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Functional characterization of Babesia bovis proteins expressed on the surface of infected erythrocytes- Toward identification of novel vaccine and therapeutic candidates

Research Project

Project/Area Number 19K15983
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionObihiro University of Agriculture and Veterinary Medicine (2020-2021)
Nagasaki University (2019)

Principal Investigator

Hakimi Hassan  帯広畜産大学, 原虫病研究センター, 特任研究員 (80745183)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsBabesia bovis / バベシア / ウシ / 赤血球 / Surface proteins / Protein export / Vaccine / Therapeutic target / Cattle
Outline of Research at the Start

The surface expressed proteins are target for immune system and considered as potential vaccine candidates.We identified 100 putative Babesia bovis surface proteins which we are planning to characterize and evaluate their feasibility to be used as novel vaccine or drug targets.

Outline of Final Research Achievements

Babesiosis has great economic impact on livestock industry in tropical and subtropical regions in the world. Combination of novel drug and vaccine intervention are required to better control the disease. Using proteomics we identified 3 novel exported proteins: The first two protein (Bb60 and Bb11920) with 10 transmembrane regions that were expressed in spherical bodies and on the surface of infected red blood cells (iRBCs). Development of Blasticidin S (BS) resistance resulted in downregulation of one major expressing gene of mtm, suggesting an association with BS uptake. Induced knockdown of the third exported protein, Bb4280, resulted in decreased growth rate, reduced ridge numbers on the erythrocyte surface, mislocalized VESA1 that is a ligand for cytoadhesion, and abrogated cytoadhesion to endothelial cells, suggesting that this protein is a novel virulence factor for B. bovis. We named this protein VESA1-export associated protein (BbVEAP).

Academic Significance and Societal Importance of the Research Achievements

本研究によりバベシア・ボビスにおいて3つの新規赤血球修飾分子を発見した。これらの分子は原虫の栄養取り込みに関わると推定されるものや、脳性バベシア症と呼ばれる致死的な症状に関与するものであることが明らかとなった。今後研究を進めることで、これらの分子は薬剤やワクチンの標的分子となる可能性がある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Distinct effects on the secretion of MTRAP and AMA1 in Plasmodium yoelii following deletion of acylated pleckstrin homology domain-containing protein2022

    • Author(s)
      Nattawat Chaiyawong, Takahiro Ishizaki, Hassan Hakimi, Masahito Asada, Kazuhide Yahata, Osamu Kaneko
    • Journal Title

      Parasitology international

      Volume: 86 Pages: 102479-102479

    • DOI

      10.1016/j.parint.2021.102479

    • NAID

      120007180593

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach2022

    • Author(s)
      Alireza Mansouri, Rasoul Kowsar, Mostafa Zakariazadeh, Hassan Hakimi, Akio Miyamoto
    • Journal Title

      Scientific reports

      Volume: 12 Issue: 1 Pages: 717-717

    • DOI

      10.1038/s41598-022-04778-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent Advances in Molecular Genetic Tools for Babesia2021

    • Author(s)
      Hassan Hakimi, H, Masahito Asada, Shinichiro Kawazu
    • Journal Title

      Veterinary Sciences

      Volume: 8 Issue: 10 Pages: 222-222

    • DOI

      10.3390/vetsci8100222

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isolation of viable Babesia bovis merozoites to study parasite invasion2021

    • Author(s)
      Hassan Hakimi, H, Masahito Asada, Takahiro Ishizaki, Shinichiro Kawazu
    • Journal Title

      Scientific reports

      Volume: 11 Issue: 1 Pages: 16959-16959

    • DOI

      10.1038/s41598-021-96365-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glycosphingolipid GM3 is localized in both exoplasmic and cytoplasmic leaflets of Plasmodium falciparum malaria parasite plasma membrane2021

    • Author(s)
      Shiomi Koudatsu, Tatsunori Masatani, Rikako Konishi, Masahito Asada, Hassan Hakimi, Yuna Kurokawa, Kanna Tomioku, Osamu Kaneko & Akikazu Fujita
    • Journal Title

      Scientific reports

      Volume: 11 Issue: 1 Pages: 14890-14890

    • DOI

      10.1038/s41598-021-94037-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] cAMP-dependent protein kinase regulates secretion of apical membrane antigen 1 (AMA1) in Plasmodium yoelii2021

    • Author(s)
      Takahiro Ishizaki, Masahito Asada, Hassan Hakimi, Nattawat Chaiyawong, Yuto Kegawa, Kazuhide Yahatab, Osamu Kaneko
    • Journal Title

      Parasitology international

      Volume: 85 Pages: 102435-102435

    • DOI

      10.1016/j.parint.2021.102435

    • NAID

      120007172255

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Babesia bovis exported proteins that modify properties of infected red blood cells2020

    • Author(s)
      Hakimi H, Templeton TJ, Sakaguchi M, Yamagishi J, Miyazaki S, Yahata K, Uchihashi T, Kawazu SI, Kaneko O, Asada M
    • Journal Title

      PLoS Pathogens

      Volume: 16(10) Issue: 10 Pages: e1008917-e1008917

    • DOI

      10.1371/journal.ppat.1008917

    • NAID

      120006988490

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation2020

    • Author(s)
      Ishizaki Takahiro、Chaiyawong Nattawat、Hakimi Hassan、Asada Masahito、Tachibana Mayumi、Ishino Tomoko、Yahata Kazuhide、Kaneko Osamu
    • Journal Title

      Parasitology International

      Volume: 76 Pages: 102056-102056

    • DOI

      10.1016/j.parint.2020.102056

    • NAID

      120006988309

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome editing of Babesia bovis using the CRISPR/Cas9 system.2019

    • Author(s)
      Hakimi, H., Ishizaki, T., Kegawa, Y., Kaneko, O., Kawazu, S., and Asada, M.
    • Journal Title

      mSphere

      Volume: 4(3) Issue: 3

    • DOI

      10.1128/msphere.00109-19

    • NAID

      120006988459

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epidemiology, risk factors, and co-infection of vector-borne pathogens in goats from Sistan and Baluchestan province, Iran2019

    • Author(s)
      Hakimi H, Sarani A, Takeda M, Kaneko O, Asada M
    • Journal Title

      PLoS One

      Volume: 14(6) Issue: 6 Pages: e0218609-e0218609

    • DOI

      10.1371/journal.pone.0218609

    • NAID

      120006987685

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Initiated Babesia ovata Sexual Stages under In Vitro Conditions Were Recognized by Anti-CCp2 Antibodies, Showing Changes in the DNA Content by Imaging Flow Cytometry2019

    • Author(s)
      Nguyen TT, Dang-Trinh MA, Higuchi L, Mosqueda J, Hakimi H, Asada M, Yamagishi J, Umemiya-Shirafuji R, Kawazu SI
    • Journal Title

      Pathogens

      Volume: 8(3) Issue: 3 Pages: 104-104

    • DOI

      10.3390/pathogens8030104

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transient transfection of Babesia ovis using heterologous promoters2019

    • Author(s)
      Rosa C, Asada M, Hakimi H, Domingos A, Pimentel M, Antunes S
    • Journal Title

      Ticks Tick Borne Dis

      Volume: 10(6) Issue: 6 Pages: 101279-101279

    • DOI

      10.1016/j.ttbdis.2019.101279

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Cyclic GMP-dependent protein kinase plays a central role for egress of Babesia bovis2021

    • Author(s)
      Hassan Hakimi, Masahito Asada, Shinichiro Kawazu
    • Organizer
      The 164th Meeting of the Japanese Society of Veterinary Sciences
    • Related Report
      2021 Annual Research Report
  • [Presentation] A novel Babesia bovis secreted protein responsible for binding of infected erythrocyte to endothelial cells2021

    • Author(s)
      Hassan Hakimi, Miako Sakaguchi, Junya Yamagishi, Shinichiro Kawazu, Osamu Kaneko, Masahito Asada
    • Organizer
      The 90th Annual Meeting of the Japanese Society of Parasitology
    • Related Report
      2020 Research-status Report
  • [Presentation] The expression of a novel multigene family is correlated with channel activity in Babesia bovis-infected erythrocytes2020

    • Author(s)
      Hassan Hakimi, Thomas J Templeton, Miako Sakaguchi, Junya Yamagishi, Kazuhide Yahata, Shinichiro Kawazu, Osamu Kaneko, Masahito Asada
    • Organizer
      The 89th Annual Meeting of the Japanese Society of Parasitology
    • Related Report
      2019 Research-status Report
  • [Presentation] A novel Babesia bovis secreted protein responsible for binding of infected erythrocyte to endothelial cells2019

    • Author(s)
      Hassan Hakimi, Miako Sakaguchi, Junya Yamagishi, Kazuhide Yahata, Osamu Kaneko, Masahito Asada
    • Organizer
      The 30th Annual Molecular Parasitology Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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