In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts.

Müller, Joachim; Balmer, Vreni; Winzer, Pablo Arnold; Rahman, Mahbubur; Manser, Vera; Haynes, Richard K; Hemphill, Andrew (2015). In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts. International journal of antimicrobial agents, 46(1), pp. 88-93. Elsevier 10.1016/j.ijantimicag.2015.02.020

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From a panel of 34 artemisinin derivatives tested in vitro, artemisone, GC007 and GC012 were most efficacious at inhibiting Neospora caninum replication (IC50 values of 3-54nM), did not notably impair the invasiveness of tachyzoites and were non-toxic for human foreskin fibroblasts (HFFs). Transmission electron microscopy of drug-treated N. caninum-infected HFFs demonstrated severe alterations in the parasite cytoplasm, changes in the composition of the matrix of the parasitophorous vacuole (PV) and diminished integrity of the PV membrane. To exert parasiticidal activity, parasites had to be cultured continuously in the presence of 5μM artemisone or GC007 for 3 weeks. N. caninum tachyzoites readily adapted to a stepwise increase in concentrations (0.5-10μM) of GC012, but not to artemisone or GC007. Drugs induced the expression of elevated levels of NcBAG1 and NcSAG4 mRNA, but only NcBAG1 could be detected by immunofluorescence. Thus, artemisinin derivatives represent interesting leads that should be investigated further.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
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; Balmer, Vreni; Winzer, Pablo Arnold; Rahman, Mahbubur; Manser, Vera and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture

ISSN:

0924-8579

Publisher:

Elsevier

Language:

English

Submitter:

Andrew Hemphill

Date Deposited:

17 Jun 2016 09:47

Last Modified:

31 Oct 2018 10:39

Publisher DOI:

10.1016/j.ijantimicag.2015.02.020

PubMed ID:

25934265

Uncontrolled Keywords:

Artemisinin, Artemisone, Chemotherapy, Neospora caninum, Resistance, Trioxolane

BORIS DOI:

10.7892/boris.82047

URI:

https://boris.unibe.ch/id/eprint/82047

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