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

• Published in: eLife Vol. 7
• Main Authors: Park, Donghyun, Lara-Tejero, Maria, Waxham, M Neal, Li, Wenwei, Hu, Bo, Galán, Jorge E, Liu, Jun
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 03.10.2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Bacteria; bacterial pathogenesis; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cell activation; Cell Membrane - metabolism; Cell Membrane - microbiology; Cell Membrane - ultrastructure; Cell membranes; Electron Microscope Tomography - methods; Gram-negative bacteria; HeLa Cells; host-pathogen interaction; Host-Pathogen Interactions; Humans; Macromolecular assembly; membrane remodeling; Microbiology and Infectious Disease; Mutation; Neurosciences; Pathogenic microorganisms; Pathogens; protein secretion; Protein Transport; Proteins; Salmonella; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Salmonella typhimurium - physiology; Secretion; Statistical analysis; Tomography; Type III Secretion Systems - genetics; Type III Secretion Systems - metabolism; Visualization; United States > US; Houston Texas; host-pathogen interaction; membrane remodeling; S. enterica; infectious disease; microbiology; bacterial pathogenesis; serovar typhie; Macromolecular assembly; protein secretion
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.39514

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 -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.