Beyond immune escape: a variant surface glycoprotein causes suramin resistance in  Trypanosoma brucei | Zendy

Wiedemar Natalie | Zendy; Graf Fabrice E. | Zendy; Zwyer Michaela | Zendy; Ndomba Emiliana | Zendy; Kunz Renggli Christina | Zendy; Cal Monica | Zendy; Schmidt Remo S. | Zendy; Wenzler Tanja | Zendy; Mäser Pascal | Zendy

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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) - biology , suramin , trypanosoma brucei , glycoprotein , immune system , virology , trypanosomiasis , trypanosoma , immune recognition , p glycoprotein , microbiology and biotechnology , immunology , drug resistance , multiple drug resistance , genetics , gene , in vitro

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.

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