Trypanosoma brucei: inhibition of cathepsin L is sufficient to kill bloodstream forms

Publication date: Available online 16 November 2019Source: Molecular and Biochemical ParasitologyAuthor(s): Dietmar Steverding, Stuart A. Rushworth, Bogdan I. Florea, Herman S. OverkleeftAbstractThe lysosomal cysteine protease activity of Trypanosoma brucei comprises a cathepsin B enzyme (TbCATB) and a cathepsin L enzyme (TbCATL). Inhibition of the cysteine protease activity is lethal to bloodstream-form trypanosomes but it was not entirely clear which of the two enzymes are essential for survival of the parasites. Here we show that the vinyl sulfone compound LU-102 selectively inhibits TbCATL without affecting TbCATB and the proteasomal trypsin-like activity within trypanosomes. Therefore, the trypanocidal activity displayed by LU-102 can be attributed solely to the inhibition of TbCATL demonstrating that this enzyme is essential to the survival of T. brucei.Graphical abstract
Source: Molecular and Biochemical Parasitology - Category: Parasitology Source Type: research