biostudies-literatureWiedemar NSwiss National Science FoundationWellcome Trust595-608https://www.ebi.ac.uk/biostudies/studies/S-EPMC6996322biostudies-literatureUnknown1(10)Suramin was introduced into the clinic a century ago and is still used to treat the first stage of acute human sleeping sickness. Due to its size and sixfold negative charge, uptake is mediated through endocytosis and the suramin receptor in trypanosomes is thought to be the invariant surface glycoprotein 75 (ISG75). Nevertheless, we recently identified a variant surface glycoprotein (VSG^Sur) that confers strong in vitro resistance to suramin in a <i>Trypanosoma brucei rhodesiense</i> line. In this study, we introduced <i>VSG^Sur</i> into the active bloodstream expression site of a <i>T. b. brucei</i> line. This caused suramin resistance and cross resistance to trypan blue. We quantified the endocytosis of different substrates by flow cytometry and showed that the exprFASEB bioAdvancesExpression of a specific variant surface glycoprotein has a major impact on suramin sensitivity and endocytosis in <i>Trypanosoma brucei</i>.PMC6996322204697/Z/16/Z310030WTI 204697/Z/16/Z156264310030_156264Field MCCal MMaser PZoltner MWiedemar NZwyer MfalseExpression of a specific variant surface glycoprotein has a major impact on suramin sensitivity and endocytosis in <i>Trypanosoma brucei</i>.Suramin was introduced into the clinic a century ago and is still used to treat the first stage of acute human sleeping sickness. Due to its size and sixfold negative charge, uptake is mediated through endocytosis and the suramin receptor in trypanosomes is thought to be the invariant surface glycoprotein 75 (ISG75). Nevertheless, we recently identified a variant surface glycoprotein (VSG^Sur) that confers strong in vitro resistance to suramin in a <i>Trypanosoma brucei rhodesiense</i> line. In this study, we introduced <i>VSG^Sur</i> into the active bloodstream expression site of a <i>T. b. brucei</i> line. This caused suramin resistance and cross resistance to trypan blue. We quantified the endocytosis of different substrates by flow cytometry and showed that the expr2019-01-01T00:00:00Z2019 Oct2025-04-04T03:33:59.783Z2020-05-22T12:00:33ZS-EPMC69963223212381110.1096/fba.2019-00033