Ungogo, M. A., Campagnaro, G. D., Alghamdi, A. H., Natto, M. J. and de Koning, H. P. (2022) Differences in transporters rather than drug targets are the principal determinants of the different innate sensitivities of Trypanosoma congolense and Trypanozoon subgenus trypanosomes to diamidines and melaminophenyl arsenicals. International Journal of Molecular Sciences, 23(5), 2844. (doi: 10.3390/ijms23052844) (PMID:35269985) (PMCID:PMC8911344)
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Abstract
The animal trypanosomiases are infections in a wide range of (domesticated) animals with any species of African trypanosome, such as Trypanosoma brucei, T. evansi, T. congolense, T. equiperdum and T. vivax. Symptoms differ between host and infective species and stage of infection and are treated with a small set of decades-old trypanocides. A complication is that not all trypanosome species are equally sensitive to all drugs and the reasons are at best partially understood. Here, we investigate whether drug transporters, mostly identified in T. b. brucei, determine the different drug sensitivities. We report that homologues of the aminopurine transporter TbAT1 and the aquaporin TbAQP2 are absent in T. congolense, while their introduction greatly sensitises this species to diamidine (pentamidine, diminazene) and melaminophenyl (melarsomine) drugs. Accumulation of these drugs in the transgenic lines was much more rapid. T. congolense is also inherently less sensitive to suramin than T. brucei, despite accumulating it faster. Expression of a proposed suramin transporter, located in T. brucei lysosomes, in T. congolense, did not alter its suramin sensitivity. We conclude that for several of the most important classes of trypanocides the presence of specific transporters, rather than drug targets, is the determining factor of drug efficacy.
| Item Type: | Articles |
|---|---|
| Keywords: | Trypanosoma congolense, Trypanosoma evansi, cymelarsan, pentamidine, suramin, diminazene, drug transporter, TbAT1, TbAQP2, MFST. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Ungogo, Mr Marzuq and De Koning, Professor Harry and Natto, Dr Manal |
| Creator Roles: | Ungogo, M. A.Methodology, Formal analysis, Investigation, Writing – original draft, Funding acquisition Natto, M. J.Methodology, Supervision, Funding acquisition de Koning, H. P.Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing – review and editing, Supervision, Funding acquisition |
| Authors: | Ungogo, M. A., Campagnaro, G. D., Alghamdi, A. H., Natto, M. J., and de Koning, H. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | International Journal of Molecular Sciences |
| Publisher: | MDPI |
| ISSN: | 1661-6596 |
| ISSN (Online): | 1422-0067 |
| Published Online: | 05 March 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in International Journal of Molecular Sciences 23(5): 2844 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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