A cell surface transporter mediates phenanthridine resistance in African trypanosomes.

Authors

Pieter C Steketee, Marzuq A Ungogo, Edith Paxton, Ella Maria Rogerson, Furaha Mramba, Michael C Pearce, Harriet K Auty, Jan Van Den Abbeele, Harry P de Koning, Catarina Gadelha, Michael P Barrett, Liam J Morrison

Published in

npj antimicrobials and resistance. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

African animal trypanosomosis poses a significant threat to livestock health and agricultural productivity across sub-Saharan Africa. Isometamidium chloride is the only available drug that is both prophylactic and curative. Despite sustained reports of resistance since the 1970s, a definitive molecular mechanism of resistance remains unresolved in the clinically relevant pathogen species Trypanosoma congolense. In this study, the role of a putative drug/metabolite transporter protein, TcoDMT, was validated via the analysis of in vitro-derived mutants, showing that expression levels of this protein correlated strongly with isometamidium sensitivity. Functional analyses revealed that the protein is a cell surface phenanthridine transporter and, notably, copy number variation correlates with isometamidium sensitivity in T. congolense field isolates. This study validates, for the first time, a plasma membrane transporter with a defined role in phenanthridine action and resistance, advancing our understanding of drug resistance mechanisms in parasitic protists, and informing strategies to combat animal trypanosomosis.

PMID:
42401745
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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