Premium
Beyond immune escape: a variant surface glycoprotein causes suramin resistance in Trypanosoma brucei
Author(s) -
Wiedemar Natalie,
Graf Fabrice E.,
Zwyer Michaela,
Ndomba Emiliana,
Kunz Renggli Christina,
Cal Monica,
Schmidt Remo S.,
Wenzler Tanja,
Mäser Pascal
Publication year - 2018
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13854
Subject(s) - suramin , trypanosoma brucei , biology , trypanosoma brucei rhodesiense , antigenic variation , trypanosomiasis , gene , trypanosoma , endocytic cycle , kinetoplastida , glycoprotein , virology , immune system , endocytosis , genetics , immunology , in vitro , receptor , protozoal disease , malaria
Summary Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense . Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T . b . brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T . brucei spp. cultures is fast, highly reproducible and linked to antigenic variation. Bloodstream‐form trypanosomes are covered by a dense coat of variant surface glycoprotein (VSG), which protects them from their mammalian hosts' immune defenses. Each T . brucei genome contains over 2000 different VSG genes, but only one is expressed at a time. An expression switch to one particular VSG, termed VSG Sur , correlated with suramin resistance. Reintroduction of the originally expressed VSG gene in resistant T . brucei restored suramin susceptibility. This is the first report of a link between antigenic variation and drug resistance in African trypanosomes.