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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.
- Source :
-
Parasitology [Parasitology] 2019 Jan; Vol. 146 (1), pp. 112-120. Date of Electronic Publication: 2018 Jun 20. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Antiprotozoal Agents administration & dosage
Cell Line
Chlorocebus aethiops
Drug Resistance
Fibroblasts
Inhibitory Concentration 50
Microscopy, Electron, Transmission
Mitochondria drug effects
Naphthoquinones administration & dosage
Sarcocystidae physiology
Sarcocystidae ultrastructure
Vero Cells
Antiprotozoal Agents pharmacology
Naphthoquinones pharmacology
Sarcocystidae drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1469-8161
- Volume :
- 146
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Parasitology
- Publication Type :
- Academic Journal
- Accession number :
- 29921336
- Full Text :
- https://doi.org/10.1017/S0031182018000975