Visualization of the type III secretion mediated Salmonella-host cell interface using cryo-electron tomography

Elife. 2018 Oct 3:7:e39514. doi: 10.7554/eLife.39514.

Abstract

Many important gram-negative bacterial pathogens use highly sophisticated type III protein secretion systems (T3SSs) to establish complex host-pathogen interactions. Bacterial-host cell contact triggers the activation of the T3SS and the subsequent insertion of a translocon pore into the target cell membrane, which serves as a conduit for the passage of effector proteins. Therefore the initial interaction between T3SS-bearing bacteria and host cells is the critical step in the deployment of the protein secretion machine, yet this process remains poorly understood. Here, we use high-throughput cryo-electron tomography (cryo-ET) to visualize the T3SS-mediated Salmonella-host cell interface. Our analysis reveals the intact translocon at an unprecedented level of resolution, its deployment in the host cell membrane, and the establishment of an intimate association between the bacteria and the target cells, which is essential for effector translocation. Our studies provide critical data supporting the long postulated direct injection model for effector translocation.

Keywords: Macromolecular assembly; S. enterica; bacterial pathogenesis; host-pathogen interaction; infectious disease; membrane remodeling; microbiology; protein secretion; serovar typhie.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Cell Membrane / microbiology
  • Cell Membrane / ultrastructure
  • Electron Microscope Tomography / methods
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Mutation
  • Protein Transport
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / physiology
  • Type III Secretion Systems / genetics
  • Type III Secretion Systems / metabolism*

Substances

  • Bacterial Proteins
  • Type III Secretion Systems