Quantitative chemical proteomics of Leishmania mexicana

We report the first systematic study of the effect of Hsp90 inhibition on the global protein synthesis in Leishmania parasites using an integrated chemical biology approach. Heat shock protein 90 (Hsp90) is a conserved molecular chaperone responsible for the folding of newly synthesised proteins. It is regarded as a master regulator of protein homeostasis of the cell, and its inhibition has been proposed to affect functions of a large array of its client proteins. We showed that the Hsp90 inhibition affects synthesis of many Leishmania proteins, with important chaperones and virulence factors showing an overall increased relative expression whilst many ribosomal proteins showing a down-regulation. This study defines the Leishmania parasite’s response to Hsp90 inhibition at its nascent global protein synthesis and provides a rich resource for future studies on Leishmania biology and antileishmanial drug development.