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In vitro treatment of Besnoitia besnoiti with the naphto-quinone buparvaquone results in marked inhibition of tachyzoite proliferation, mitochondrial alterations and rapid adaptation of tachyzoites to increased drug concentrations

Published online by Cambridge University Press:  20 June 2018

Joachim Müller ,
Vera Manser  and
Andrew Hemphill Open the ORCID record for Andrew Hemphill [Opens in a new window]
Joachim Müller
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
Vera Manser
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
Andrew Hemphill
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
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Abstract

We here assessed the in vitro efficacy of the naptho-quinone buparvaquone (BPQ) against Besnoitia besnoiti tachyzoites in vitro. BPQ is currently licensed for the treatment of theileriosis in cattle in many countries, but not in the EU. In 4-day treatment assays, BPQ massively impaired tachyzoite proliferation with an IC50 of 10 ± 3 nm, and virtually complete inhibition was obtained in the presence of nm BPQ. Exposure to 1 µm BPQ leads to ultrastructural changes affecting initially the mitochondrial matrix and the cristae. After 96 h, most parasites were largely distorted, filled with cytoplasmic amylopectin granules and vacuoles containing components of unknown composition. Host cell mitochondria did not appear to be notably affected by the drug. However, upon prolonged exposure (14–16 days) to increased BPQ concentrations, B. besnoiti tachyzoites exhibited the capacity to adapt, and they resumed proliferation at dosages of up to 10 µm BPQ, albeit at a lower rate. These BPQ-adapted parasites maintained this lower susceptibility to BPQ treatment after freeze–thawing, and inspection by the transmission electron microscopy revealed that they underwent proliferation in the absence of structurally intact mitochondria.

Keywords

Bovine besnoitiosisbuparvaquonedrug adaptationelectron microscopyin vitro treatmentmitochondrion
Type
Research Article
Information
Parasitology , Volume 146 , Issue 1 , January 2019 , pp. 112 - 120
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

Both the authors contributed equally to this work.

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