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Resistance towards monensin is proposed to be acquired in a Toxoplasma gondii model by reduced invasion and egress activities, in addition to increased intracellular replication

Published online by Cambridge University Press:  05 September 2017

AHMED THABET ,
JOHANNES SCHMIDT ,
SVEN BAUMANN ,
WALTHER HONSCHA ,
MARTIN VON BERGEN ,
ARWID DAUGSCHIES  and
BERIT BANGOURA
AHMED THABET
Affiliation:
Institute of Parasitology, Faculty of Veterinary Medicine, Centre for Infectious Diseases, University of Leipzig, Leipzig, Germany
JOHANNES SCHMIDT
Affiliation:
Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ, Leipzig, Germany
SVEN BAUMANN
Affiliation:
Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ, Leipzig, Germany Institute of Pharmacy, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany
WALTHER HONSCHA
Affiliation:
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
MARTIN VON BERGEN
Affiliation:
Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research – UFZ, Leipzig, Germany Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany Department of Chemistry and Bioscience, Center for Microbial Communities, University of Aalborg, Aalborg East, Denmark
ARWID DAUGSCHIES
Affiliation:
Institute of Parasitology, Faculty of Veterinary Medicine, Centre for Infectious Diseases, University of Leipzig, Leipzig, Germany Albrecht-Daniel-Thaer-Institute, Leipzig, Germany
BERIT BANGOURA*
Affiliation:
Institute of Parasitology, Faculty of Veterinary Medicine, Centre for Infectious Diseases, University of Leipzig, Leipzig, Germany University of Wyoming, Department of Veterinary Sciences, Laramie, WY, USA
*
*Corresponding author: Department of Veterinary Sciences, WSVL, 1174 Snowy Range Rd, 82070 Laramie, WY, USA. E-mail: [email protected]
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Summary

Monensin (Mon) is an anticoccidial polyether ionophore widely used to control coccidiosis. The extensive use of polyether ionophores on poultry farms resulted in widespread resistance, but the underlying resistance mechanisms are unknown in detail. For analysing the mode of action by which resistance against polyether ionophores is obtained, we induced in vitro Mon resistance in Toxoplasma gondii-RH strain (MonR-RH) and compared it with the sensitive parental strain (Sen-RH). The proteome assessment of MonR-RH and Sen-RH strains was obtained after isotopic labelling using stable isotope labelling by amino acid in cell culture. Relative proteomic quantification between resistant and sensitive strains was performed using liquid chromatography-mass spectrometry/mass spectrometry. Overall, 1024 proteins were quantified and 52 proteins of them were regulated. The bioinformatic analysis revealed regulation of cytoskeletal and transmembrane proteins being involved in transport mechanisms, metal ion-binding and invasion. During invasion, actin and microneme protein 8 (MIC8) are seem to be important for conoid extrusion and forming moving junction with host cells, respectively. Actin was significantly upregulated, while MIC8 was downregulated, which indicate an invasion reduction in the resistant strain. Resistance against Mon is not a simple process but it involves reduced invasion and egress activity of T. gondii tachyzoites while intracellular replication is enhanced.

Keywords

Toxoplasma gondiistable isotope labelling by amino acid in cell culturemonensinresistance mechanismSILAC
Type
Research Article
Information
Parasitology , Volume 145 , Issue 3 , March 2018 , pp. 313 - 325
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Copyright
Copyright © Cambridge University Press 2017 

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