- Which are the molecular players of active host cell exit?
During decades, T. cruzi exit has been attributed to the extensive parasite motility, thought to be sufficient to induce mechanical rupture of the host cell membrane. However, recent work has revealed that T. cruzi egress is an event driven by the parasite. As for many intracellular pathogens, the timing and mechanisms underlying T. cruzi egress are temporally controlled and very much parasite specific. By combining genetic manipulation and cutting-edge mass spectrometry technologies, we aim to identify and functionally characterized the molecular players driving the sudden host cell lysis and parasite release in T. cruzi.
THEME: “CELLULAR TRANSFORMATION”
During its life cycle in a mammalian host, T. cruzi alternates between its infective form, the trypomastigote, and its replicative form, the amastigote. Upon host cell invasion, trypomastigotes undergo drastic morphological and molecular changes to transform into amastigotes, initiating replication within their intracellular niche. At the end of the lytic cycle, intracellular amastigotes transition back to the infective trypomastigote form, in a semi-concerted manner. This process leaves the host cell filled with motile, infectious trypomastigotes, which are then released upon egress, to initiate a new lytic cycle.
This transformation, known as trypomastigogenesis, is a pivotal step in the parasite's life cycle, enabling it to spread within the host and sustain infection. It involves profound changes in the parasite's structure and function to adapt to its role as an infectious agent.
Leveraging Ultra-Expansion Microscopy (U-ExM), transgenic reporter strains, and genetic tools, we investigate the cellular structural reorganizations and molecular pathways driving the transition from replicative to infective forms. This work aims to uncover pathways that govern changes in cell shape, structure, and function. Such stage transitions are widely observed in other eukaryotic cells, and understanding these processes can illuminate the evolutionary and molecular mechanisms behind stage-specific adaptations.