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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
The adaptive potential of a survival artist: Characterization of the in vitro interactions of Toxoplasma gondii tachyzoites with di-cationic compounds in human fibroblast cell cultures
Parasitology, Volume 139, No. 2, Year 2012
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Description
The impact of di-cationic pentamidine-analogues against Toxoplama gondii (Rh- and Me49-background) was investigated. The 72 h-growth assays showed that the arylimidamide DB750 inhibited the proliferation of tachyzoites of T. gondii Rh and T. gondii Me49 with an IC 50 of 0.11 and 0.13 μm, respectively. Pre-incubation of fibroblast monolayers with 1 μm DB750 for 12 h and subsequent culture in the absence of the drug also resulted in a pronounced inhibiton of parasite proliferation. However, upon 5-6 days of drug exposure, T. gondii tachyzoites adapted to the compound and resumed proliferation up to a concentration of 1.2 μm. Out of a set of 32 di-cationic compounds screened for in vitro activity against T. gondii, the arylimidamide DB745, exhibiting an IC 50 of 003 μm and favourable selective toxicity was chosen for further studies. DB745 also inhibited the proliferation of DB750-adapted T. gondii (IC 50=0.07 μm). In contrast to DB750, DB745 also had a profound negative impact on extracellular non-adapted T. gondii tachyzoites, but not on DB750-adapted T. gondii. Adaptation of T. gondii to DB745 (up to a concentration of 0.46 μm) was much more difficult to achieve and feasible only over a period of 110 days. In cultures infected with DB750-adapted T. gondii seemingly intact parasites could occasionally be detected by TEM. This illustrates the astonishing capacity of T. gondii tachyzoites to adapt to environmental changes, at least under in vitro conditions, and suggests that DB745 could be an interesting drug candidate for further assessments in appropriate in vivo models. © 2011 Cambridge University Press.
Authors & Co-Authors
Kropf, Christian
Switzerland, Bern
University of Bern
Debache, Karim
Switzerland, Bern
University of Bern
Rampa, Christoph
Switzerland, Bern
University of Bern
Barna, Fabienne
Switzerland, Bern
University of Bern
Schorer, Michelle
Switzerland, Bern
University of Bern
Stephens, Chad E.
United States, Augusta
Augusta State University
Ismail, Mohamed A.
United States, Atlanta
Georgia State University
Saudi Arabia, Al-ahsa
King Faisal University
Boykin, David Withers
United States, Atlanta
Georgia State University
Hemphill, Andrew
Switzerland, Bern
University of Bern
Statistics
Citations: 30
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.1017/S0031182011001776
e-ISSN:
14698161