Suramin is a fascinating molecule. It is probably the first drug developed in a medicinal chemistry program (Bayer, 1916) and still the treatment of choice for the haemo-lymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Somewhat surprisingly, suramin-resistant T. brucei bloodstream forms are quickly and reproducibly selected for in culture. More surprisingly, all the suramin-resistant trypanosomes have switched to express the same variant surface glycoprotein, termed VSGSur, although each cell has more than 1000 VSG genes. This is the first described link between antigenic variation and drug resistance in African trypanosomes. The most obvious explanation is that one of the VSG expression site-associated genes is responsible for the suramin resistance phenotype. However, we think that VSGSur itself causes suramin resistance – evidence shall be presented.
Pascal Mäser is associate professor for parasitology and protozoology at the University of Basel and head of the parasite chemotherapy unit of the Swiss TPH. His research focuses on drug discovery for trypanosomatid parasites and malaria.