Proteome-Wide Analysis of Trypanosoma cruzi Exponential and Stationary Growth Phases Reveals a Subcellular Compartment-Specific Regulation

Abstract

Trypanosoma cruzi, the etiologic agent of Chagas disease, cycles through different life stages characterized by defined molecular traits associated with the proliferative or differentiation state. In particular, T. cruzi epimastigotes are the replicative forms that colonize the intestine of the Triatomine insect vector before entering the stationary phase that is crucial for differentiation into metacyclic trypomastigotes, which are the infective forms of mammalian hosts. The transition from proliferative exponential phase to quiescent stationary phase represents an important step that recapitulates the early molecular events of metacyclogenesis, opening new possibilities for understanding this process. In this study, we report a quantitative shotgun proteomic analysis of the T. cruzi epimastigote in the exponential and stationary growth phases. More than 3000 proteins were detected and quantified, highlighting the regulation of proteins involved in different subcellular compartments. Ribosomal proteins were upregulated in the exponential phase, supporting the higher replication rate of this growth phase. Autophagy-related proteins were upregulated in the stationary growth phase, indicating the onset of the metacyclogenesis process. Moreover, this study reports the regulation of N-terminally acetylated proteins during growth phase transitioning, adding a new layer of regulation to this process. Taken together, this study reports a proteome-wide rewiring during T. cruzi transit from the replicative exponential phase to the stationary growth phase, which is the preparatory phase for differentiation.

Structure, Properties, and Function of Glycosomes in Trypanosoma cruzi

“…cruzi, like other dixenous trypanosomatid parasites, undergoes an elaborate life cycle involving extracellular replicative epimastigotes in the triatomine digestive tube, non-replicative extracellular metacyclic and bloodstream trypomastigotes in the insect and mammalian host, respectively, and replicative amastigotes intracellularly in the cytosol of the mammalian cells. The different developmental stages differ importantly in morphology, but also in metabolism to adapt to the large nutritional conditions encountered in the different niches (Maugeri et al, 2011;Barisón et al, 2017;Avila et al, 2018;Marchese et al, 2018;Mattos et al, 2019). Since glycosomes harbor many enzymes of intermediary metabolism as well as enzymes of other metabolic processes which are differentially expressed, glycosomal metabolism has to undergo reprogramming.…”

Role of Proteomics in the Study of Trypanosoma cruzi Biology

“…Otherwise, this paper reported the regulation of N-terminally acetylated proteins during growth phase transitioning, adding a new layer of regulation to this process. Thus, this paper reported a proteome-wide rewiring during T. cruzi differentiation from the EPIs' proliferative exponential phase to the stationary growth phase, which is the step before cell transformation into the MT stage [36].…”

Proteomic Insights into the Biology of the Most Important Foodborne Parasites in Europe

“…Next study indicated that during periods of nutritional stress, many proteins are phosphorylated, which may trigger metacyclogenesis [ 150 ]. Similarly, the proteomic comparison of the exponential phase and stationary phase of the epimastigotes quantified more than 3000 proteins [ 151 ]. The transition from trypomastigotes to amastigotes (amastigogenesis) was described by quantitative proteomics and phosphoproteomics [ 152 , 153 ].…”