Trypanosoma cruzi LC-MSMS - 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

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

克氏锥虫（Trypanosoma cruzi）是恰加斯病（Chagas disease）的致病因子，其生命周期历经不同发育阶段，各阶段以与增殖或分化状态相关的明确分子特征为标识。具体而言，克氏锥虫上鞭毛体（epimastigotes）为增殖型虫体，可定植于锥蝽（Triatomine）媒介昆虫的肠道内，随后进入静止期；该静止期是分化为循环传播型锥鞭毛体（metacyclic trypomastigotes）的关键阶段，而后者是感染哺乳动物宿主的感染型虫体。从增殖指数期到静息静止期的转变是一项重要进程，该过程重现了循环分化（metacyclogenesis）的早期分子事件，为解析这一过程开辟了新的研究可能。本研究针对指数生长期与静止生长期的克氏锥虫上鞭毛体开展了定量鸟枪法蛋白质组学（shotgun proteomic）分析，共检测并定量到3000余种蛋白质，揭示了不同亚细胞区室相关蛋白质的调控模式。核糖体蛋白质在指数生长期显著上调，印证了该阶段更高的复制速率；自噬相关蛋白质在静止生长期上调，提示循环分化过程已然启动。此外，本研究还报道了生长阶段转换过程中N末端乙酰化蛋白质（N-terminally acetylated proteins）的调控情况，为该过程新增了一层调控维度。综上，本研究揭示了克氏锥虫从增殖型指数生长期到作为分化准备阶段的静止生长期过程中，全蛋白质组的重编程现象。