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The ABL kinase inhibitor imatinib causes phenotypic changes and lethality in adult Schistosoma japonicum

  • Xuesong Li
  • Simone Haeberlein
  • Lu Zhao
  • Mudassar N. Mughal
  • Tao Zhu
  • Lu Liu
  • Rui Fang
  • Yanqin Zhou
  • Junlong Zhao
  • Christoph G. Grevelding
  • Min HuEmail author
Helminthology - Original Paper

Abstract

Schistosomiasis caused by different species of schistosome parasites is one of the most debilitating helminthic diseases of humans worldwide. For decades, chemotherapy is the main method of controlling schistosomiasis. However, the fear of drug resistance has motivated the search for alternatives. It has been demonstrated that the ABL kinase inhibitor imatinib affected the development and survival of Schistosoma mansoni in vitro; however, there is still lack of information on whether imatinib also affects other schistosome species such as Schistosoma japonicum. In the present study, the anti-schistosomal potency of imatinib on adult S. japonicum was investigated in vitro, and the results showed that imatinib had a significant impact on various physiological processes of S. japonicum adult worms. Besides its negative effects on worm motility, pairing stability, and gonad development, imatinib caused pathological changes in the gastrodermis as well as the death of the parasite. Our findings suggest that imatinib is an intriguing candidate for further development as an option to fight S. japonicum.

Keywords

Imatinib ABL kinases Schistosoma japonicum Development In vitro culture 

Abbreviations

PZQ

Praziquantel

S. japonicum

Schistosoma japonicum

S. mansoni

Schistosoma mansoni

PTKs

Protein tyrosine kinases

ABL

Abelson

CML

Chronic myelogenous leukemia

cKIT

Proto-oncogene receptor tyrosine kinase

PDGF-R

Platelet-derived growth factor receptors

Imatinib

Imatinib mesylate

CLSM

Confocal laser scanning microscopy

Notes

Authors’ contributions

Conceived and designed the experiments: SH, CGG, and MH. Performed the experiments: XS, LZ, MM, TZ, and LL. Analyzed the data: XS, SH, LZ, CGG, and MH. Contributed reagents/materials/analysis tools: RF, YQZ, and JLZ. Wrote the paper: XS, SH, LZ, CGG, and MH. All authors read and approved the final manuscript.

Funding

This work was supported by grants from the National Key Basic Research Program (973 program) of China (grant no. 2015CB150300) and the Fundamental Research Funds for the Central Universities (grant no. 2662017PY084) to MH and the Huazhong Agricultural University Scientific & Technological Self Innovation Foundation (Program no. 2015RC005) to MH, RF, YQZ, and JLZ.

Compliance with ethical standards

Ethical approval and consent to participate

The conduct and procedures involving animal experimentation in this study were approved by the Scientific Ethics Committee of Huazhong Agricultural University (HZAUMO-2017-024) according to the regulations for the Administration of Affairs Concerning Experimental Animals of Hubei Province.

Conflict of interests

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Agricultural Microbiology, College of Veterinary MedicineHuazhong Agricultural UniversityWuhanPeople’s Republic of China
  2. 2.Institute of Parasitology, BFSJustus-Liebig-University GiessenGiessenGermany

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