Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance

Bernhard, Sonja; Nerima, Barbara; Mäser, Pascal; Brun, Reto (2007). Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance. International journal for parasitology, 37(13), pp. 1443-8. Kidlington, UK: Elsevier 10.1016/j.ijpara.2007.05.007

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Resistance to melarsoprol and pentamidine was induced in bloodstream-form Trypanosoma brucei rhodesiense STIB 900 in vitro, and drug sensitivity was determined for melarsoprol, pentamidine and furamidine. The resistant populations were also inoculated into immunosuppressed mice to verify infectivity and to monitor whether rodent passage selects for clones with altered drug sensitivity. After proliferation in the mouse, trypanosomes were isolated and their IC(50) values to the three drugs were determined. To assess the stability of drug-induced resistance, drug pressure was ceased for 2 months and the drug sensitivity was determined again. Resistance was stable, with a few exceptions that are discussed. Drug IC(50)s indicated cross-resistance among all drugs, but to varying extents: resistance of the melarsoprol-selected and pentamidine-selected trypanosomes to pentamidine was the same, but the pentamidine-selected trypanosome population showed lower resistance to melarsoprol than the melarsoprol-selected trypanosomes. Interestingly, both resistant populations revealed the same intermediate cross-resistance to furamidine. Resistant trypanosome populations were characterised by molecular means, referring to the status of the TbAT1 gene. The melarsoprol-selected population apparently had lost TbAT1, whereas in the pentamidine-selected trypanosome population it was still present.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Mäser, Pascal

ISSN:

0020-7519

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:57

Last Modified:

17 Mar 2015 22:06

Publisher DOI:

10.1016/j.ijpara.2007.05.007

Web of Science ID:

000250182800003

URI:

https://boris.unibe.ch/id/eprint/24693 (FactScience: 52831)

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