Authors
M Zoltner4; S Vaughan1; C Gadelha3; K F Leung2; L S Guther4; A Burrell1; L Ali4; M A Ferguson4; M C Field4; 1 Department of Biological and Medical Sciences, Oxford Brookes University, Oxford; 2 Department of Pathology, University of Cambridge, Cambridge; 3 Queen's Medical Centre, University of Nottingham, Nottingham; 4 Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee Discussion
Suramin, a key trypanosomiasis drug developed over a century ago, remains in the clinic for treatment of early stage disease, while its mode of action is elusive. Recent studies suggest a prominent role of endocytosis for suramin uptake and we investigated the effect of suramin on Trypanosoma brucei at the ultrastructural level using transmission and serial-block-phase scanning electron microscopy. After two days of suramin treatment, cells begin to exhibit morphological abnormalities, which included enlargement of the flagellar pocket. However, the most striking alteration was a significant increase in the volume of glycosomes. Surprisingly, suramin did not lead to a corresponding increase of glycosomal proteins, but a decrease in the glycosomal UDP-glucose 4’-isomerase TbGalE and homologs of peroxisome biogenesis factors 2 and 12. The most prominent protein abundance changes were upregulation of the plasma membrane glucose transporter THT1 and a protein cohort involved in differentiation to stumpy form, including PAD isoforms and the receptor-type adenylyl cyclase GRESAG4. Analysis of sugar nucleotide pools revealed reduced levels of UDP-α-D-N-acetylglucosamine upon suramin treatment, while the four remaining sugar nucleotides were not significantly perturbed. Our data identify for the first time a specific metabolic process impacted by suramin. 
