Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo

PLoS Pathog. 2018 Mar 9;14(3):e1006925. doi: 10.1371/journal.ppat.1006925. eCollection 2018 Mar.


Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to the pathogenesis of human Salmonella infection. They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site for infection. Their function in vivo has remained ill-defined due to the lack of a suitable animal model that allows visualization of intraepithelial Salmonella. Here, we took advantage of our novel neonatal mouse model and analyzed various bacterial mutants and reporter strains as well as gene deficient mice. Our results demonstrate the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo. In contrast, the generation of a replicative intraepithelial endosomal compartment required the cooperative action of SipA and SopE2 or SipA and SopB but was independent of SopA or host MyD88 signaling. Intraepithelial growth had no critical influence on systemic spread. Our results define the role of SPI1-T3SS effector molecules during enterocyte invasion and intraepithelial proliferation in vivo providing novel insight in the early course of Salmonella infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Proliferation
  • Enterocytes / metabolism
  • Enterocytes / microbiology*
  • Enterocytes / pathology
  • Genetic Complementation Test
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / physiology*
  • Salmonella Infections / metabolism
  • Salmonella Infections / microbiology*
  • Salmonella typhimurium / pathogenicity*
  • Signal Transduction
  • Type III Secretion Systems / genetics
  • Type III Secretion Systems / metabolism*


  • Bacterial Proteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Spi1 protein, Salmonella
  • Type III Secretion Systems

Grant support

This work was supported by: German Research Foundation ( Priority Program 1580 “Intracellular Compartments as Places of Pathogen - Host Interaction” to MWH and MH, the German Research Foundation Individual Grant Ho-2236/12-1, Ho-2236/8-1 and Ho-2236/14-1 to MHo. the German Research Foundation Individual Grant HE1964/18-2 and the Collaborative Research Center SFB 944 (P4) to MHe, and the German Research Foundation Individual Grant To-1052/1-1 to NT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.