Related Experiment Video
Updated: May 16, 2026
Isolation of Salmonella typhimurium-containing Phagosomes from Macrophages
Published on: October 25, 2017
Attenuated Salmonella Typhimurium lacking the pathogenicity island-2 type 3 secretion system grow to high bacterial
Andrew J Grant1, Fiona J E Morgan, Trevelyan J McKinley
1Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom. ajg60@cam.ac.uk
Abstract:
Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonella enterica. By observing infection dynamics at the single-cell level in vivo, we have discovered that the Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is dispensable for growth to high intracellular densities. This challenges the concept that intracellular replication absolutely requires proteins delivered by SPI-2 T3SS, which has been derived largely by inference from in vitro cell experiments and from unrefined measurement of net growth in mouse organs. Furthermore, we infer from our data that the SPI-2 T3SS mediates exit from infected cells, with consequent formation of new infection foci resulting in bacterial spread in the tissues. This suggests a new role for SPI-2 in vivo as a mediator of bacterial spread in the body. In addition, we demonstrate that very similar net growth rates of attenuated salmonellae in organs can be derived from very different underlying intracellular growth dynamics.
Insights
Salmonella enterica virulence relies on intracellular growth and spread. The Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is not essential for high-density intracellular growth but mediates bacterial spread in tissues.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Salmonella enterica virulence depends on intracellular replication and cell-to-cell spread.
- The Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is traditionally considered crucial for intracellular growth.
Purpose of the Study:
- To investigate the role of SPI-2 T3SS in Salmonella enterica intracellular replication and spread in vivo.
- To challenge existing paradigms regarding SPI-2 T3SS function in bacterial pathogenesis.
Main Methods:
- In vivo single-cell imaging of infection dynamics.
- Analysis of bacterial growth and spread within host tissues.
Main Results:
- SPI-2 T3SS is dispensable for Salmonella enterica achieving high intracellular densities.
- SPI-2 T3SS mediates bacterial exit from infected cells, facilitating tissue spread.
- Net growth rates can mask diverse underlying intracellular dynamics.
Conclusions:
- The SPI-2 T3SS's primary role in vivo may be mediating bacterial spread rather than intracellular replication.
- Re-evaluation of SPI-2 T3SS function in Salmonella pathogenesis is warranted.
- In vivo single-cell dynamics provide a more nuanced understanding of bacterial virulence.
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:18Bacterial Gastroenteritis