Comparative Proteomic Analysis of Lysine Acetylation in Trypanosomes

Abstract

Protein acetylation is a post-translational modification regulating diverse cellular processes. By using proteomic approaches, we identified N-terminal and ε-lysine acetylated proteins in Trypanosoma cruzi and Trypanosoma brucei, which are protozoan parasites that cause significant human and animal diseases. We detected 288 lysine acetylation sites in 210 proteins of procyclic form, an insect stage of T. brucei, and 380 acetylation sites in 285 proteins in the form of the parasite that replicates in mammalian bloodstream. In T. cruzi insect proliferative form we found 389 ε-lysine-acetylated sites in 235 proteins. Notably, we found distinct acetylation profiles according to the developmental stage and species, with only 44 common proteins between T. brucei stages and 18 in common between the two species. While K-ac proteins from T. cruzi are enriched in enzymes involved in oxidation/reduction balance, required for the parasite survival in the host, in T. brucei, most K-ac proteins are enriched in metabolic processes, essential for its adaptation in its hosts. We also identified in both parasites a quite variable N-terminal acetylation sites. Our results suggest that protein acetylation is involved in differential regulation of multiple cellular processes in Trypanosomes, contributing to our understanding of the essential mechanisms for parasite infection and survival.

Role of Proteomics in the Study of Trypanosoma cruzi Biology

“…Lysine-acetylated protein sites were enriched in enzymes involved in oxidation/reduction balance, which is required for parasite survival in the host. These observations provide evidence that in T. cruzi, protein acetylation participates in the differential regulation of several cellular pathways and helps elucidate the mechanisms involved in parasite infection and survival [44].…”

The endoplasmic reticulum-associated mRNA-binding proteins ERBP1 and ERBP2 interact in bloodstream-formTrypanosoma brucei

“…Cells containing only a single tetracycline-inducible copy of ERBP1-myc (inducible on a knock-out background, cKO) grew at similar rates to wild-type with or without tetracycline, but the protein was clearly detectable in the absence of induction. The double band from ERBP1 was not always seen but might be caused by acetylation (Moretti et al, 2018) or phosphorylation (Urbaniak, Martin & Ferguson, 2013). Despite these initial results, upon prolonged cultivation, the cells lacking ERBP1 gradually increased their growth rate to wild-type.…”

Peer Review #2 of "The endoplasmic reticulum-associated mRNA-binding proteins ERBP1 and ERBP2 interact in bloodstream-form Trypanosoma brucei (v0.1)"

“…Cells containing only a single tetracycline-inducible copy of ERBP1-myc (inducible on a knockout background, cKO) grew at similar rates to wild-type with or without tetracycline, but the protein was clearly detectable in the absence of induction. The double band from ERBP1 was not always seen but might be caused by acetylation (Moretti et al 2018) or phosphorylation (Urbaniak et al 2013). Despite these initial results, upon prolonged cultivation, the cells lacking ERBP1 gradually increased their growth rate to wild-type.…”