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.

Müller, Joachim; Manser, Vera; Hemphill, Andrew (2019). 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. Parasitology, 146(1), pp. 112-120. Cambridge University Press 10.1017/S0031182018000975

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Müller, Joachim; Manser, Vera and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

0031-1820

Publisher:

Cambridge University Press

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Andrew Hemphill

Date Deposited:

25 Apr 2019 07:58

Last Modified:

24 Oct 2019 07:43

Publisher DOI:

10.1017/S0031182018000975

PubMed ID:

29921336

Additional Information:

HOPA RPF

Uncontrolled Keywords:

Bovine besnoitiosis buparvaquone drug adaptation electron microscopy in vitro treatment mitochondrion

BORIS DOI:

10.7892/boris.127310

URI:

https://boris.unibe.ch/id/eprint/127310

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