Reorganization of the endosomal system in Salmonella-infected cells: the ultrastructure of Salmonella-induced tubular compartments

PLoS Pathog. 2014 Sep 25;10(9):e1004374. doi: 10.1371/journal.ppat.1004374. eCollection 2014 Sep.

Abstract

During the intracellular life of Salmonella enterica, a unique membrane-bound compartment termed Salmonella-containing vacuole, or SCV, is formed. By means of translocated effector proteins, intracellular Salmonella also induce the formation of extensive, highly dynamic membrane tubules termed Salmonella-induced filaments or SIF. Here we report the first detailed ultrastructural analyses of the SCV and SIF by electron microscopy (EM), EM tomography and live cell correlative light and electron microscopy (CLEM). We found that a subset of SIF is composed of double membranes that enclose portions of host cell cytosol and cytoskeletal filaments within its inner lumen. Despite some morphological similarities, we found that the formation of SIF double membranes is independent from autophagy and requires the function of the effector proteins SseF and SseG. The lumen of SIF network is accessible to various types of endocytosed material and our CLEM analysis of double membrane SIF demonstrated that fluid phase markers accumulate only between the inner and outer membrane of these structures, a space continual with endosomal lumen. Our work reveals how manipulation of the endosomal membrane system by an intracellular pathogen results in a unique tubular membrane compartmentalization of the host cell, generating a shielded niche permissive for intracellular proliferation of Salmonella.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Bacterial Proteins / metabolism
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / ultrastructure
  • Macrophages / microbiology
  • Macrophages / pathology*
  • Mice
  • Microscopy, Electron, Transmission
  • Phagocytosis / physiology
  • Protein Transport
  • Salmonella / physiology*
  • Salmonella Infections / metabolism*
  • Salmonella Infections / microbiology
  • Salmonella Infections / pathology
  • Vacuoles / metabolism*
  • Vacuoles / ultrastructure

Substances

  • Bacterial Proteins

Grant support

This work was funded by the DFG by grant HE1964/18-1 and SFB944 project Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.