Parasite-mediated remodeling of the host microfilament cytoskeleton enables rapid egress of Trypanosoma cruzi following membrane rupture

Eden R. Ferreira, Alexis Bonfim-Melo, Barbara A. Burleigh, Jaime A. Costales, Kevin M. Tyler, Renato A. Mortara

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Abstract

Chagas’ disease arises as a direct consequence of the lytic cycle of Trypanosoma cruzi in the mammalian host. While invasion is well studied for this patho-gen, study of egress has been largely neglected. Here, we provide the first description of T. cruzi egress documenting a coordinated mechanism by which T. cruzi engineers its escape from host cells in which it has proliferated and which is essential for mainte-nance of infection and pathogenesis. Our results indicate that this parasite egress is a sudden event involving coordinated remodeling of host cell cytoskeleton and subsequent rupture of host cell plasma membrane. We document that host cells maintain plasma membrane integrity until immediately prior to parasite release and report the sequential transformation of the host cell’s actin cytoskeleton from normal meshwork in noninfected cells to spheroidal cages—a process initiated shortly after amastigogenesis. Quantification revealed gradual reduction in F-actin over the course of infection, and using cytoskeletal preparations and electron microscopy, we were able to observe disruption of the F-actin proximal to intracellular trypomastigotes. Finally, Western blotting experiments suggest actin degradation driven by parasite proteases, suggesting that degradation of cytoskeleton is a principal component controlling the initiation of egress. Our results provide the first description of the cellular mechanism that regulates the lytic component of the T. cruzi lytic cycle. We show graphically how it is possible to pre-serve the envelope of host cell plasma membrane during intracellular proliferation of the parasite and how, in cells packed with amastigotes, differentiation into trypomasti-gotes may trigger sudden egress.

Original languageEnglish
Article numbere00988-21
JournalmBIO
Volume12
Issue number3
Early online date22 Jun 2021
DOIs
Publication statusPublished - 7 Jul 2021

Keywords

  • Chagas’ disease
  • Trypanosoma cruzi
  • amastigote
  • cell invasion
  • egress
  • host-parasite relationship
  • lytic cycle
  • microfilament
  • protozoan
  • stage-regulated
  • trypomastigote
  • Microfilament
  • Protozoan
  • Egress
  • Lytic cycle
  • Stage-regulated
  • Cell invasion
  • Host-parasite relationship
  • Trypomastigote
  • Amastigote

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