Opisthorchis felineus genes differentially expressed under praziquantel shed light on the nature of tegument disruption and indicate the adaptive role of cGMP-dependent protein kinase

Abstract

Opisthorchis felineus is a trematode flatworm that parasitises mammals, including humans, and is mainly spread throughout Eastern Europe and Western Siberia. The main drug used in treatment of opisthorchiasis and other trematode and cestode infestations is praziquantel (PZQ). We provide a possible explanation of PZQ-mediated tegument disruption. The idea is that the nature of tegument disruption is related to failure of surface renovation due to insufficiency of microtubule transport of vesicles. This insufficiency arises from microtubule destabilisation, which in the medium term leads to the decrease in tubulins alpha, beta and dynein mRNA amounts and deficiency of the corresponding proteins. We also found the upregulation of cGMP-dependent protein kinase gene, and we concluded that its protein product helped to overcome the effect of praziquantel and might be a promising target for combined anthelmintic therapy with PZQ. We concluded that function of saposin-like protein 2 (SAP2) is unlikely associated with membrane fusion, and SAP2 is probably able to bind some type of hydrophobic compounds including praziquantel.

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Funding

This work was supported by RF Budget project number 0324-2019-0041-C-01.

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Correspondence to Daria Pirozhkova.

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Pirozhkova, D., Katokhin, A. Opisthorchis felineus genes differentially expressed under praziquantel shed light on the nature of tegument disruption and indicate the adaptive role of cGMP-dependent protein kinase. Parasitol Res (2020). https://doi.org/10.1007/s00436-020-06764-7

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Keywords

  • Opisthorchis felineus
  • Praziquantel
  • Gene expression
  • Microtubule-based transport
  • Tegument disruption
  • Drug target