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Updated: Oct 1, 2026

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
11:10

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages

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Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella from reactive nitrogen

Dipshikha Chakravortty1, Imke Hansen-Wester, Michael Hensel

  • 1Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.

The Journal of Experimental Medicine
|May 8, 2002
PubMed

Insights

Salmonella typhimurium uses its SPI2 system to avoid nitric oxide synthase (iNOS) and reactive nitrogen intermediates (RNI). This mechanism is crucial for bacterial survival within macrophages and systemic infection.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Salmonella typhimurium infection in mice mimics human typhoid fever.
  • The Salmonella Pathogenicity Island 2 (SPI2) type III secretion system is vital for virulence and intracellular survival.
  • Inducible nitric oxide synthase (iNOS) produces reactive nitrogen intermediates (RNI) that combat intracellular pathogens like S. typhimurium.

Purpose of the Study:

  • To investigate how Salmonella infection impacts iNOS activity in macrophages.
  • To determine the role of the SPI2 system in Salmonella's interaction with iNOS and RNI.

Main Methods:

  • Immunofluorescence microscopy to visualize iNOS and bacterial colocalization.
  • Analysis of nitrotyrosine residue localization as an indicator of peroxynitrite presence.
  • Genetic manipulation of Salmonella, including SPI2 mutants and iNOS-deficient mice.

Main Results:

  • SPI2-deficient Salmonella efficiently colocalized with iNOS, unlike wild-type bacteria.
  • The SPI2 system prevents peroxynitrite from entering Salmonella-containing vacuoles.
  • Inhibition of iNOS enhanced the intracellular proliferation of both SPI2 mutants and wild-type Salmonella.
  • Absence of iNOS partially restored systemic infection in SPI2 mutant-infected mice.

Conclusions:

  • The SPI2 type III secretion system actively excludes iNOS and RNI from Salmonella-containing vacuoles.
  • Avoiding RNI colocalization is a key adaptation strategy for intracellular bacterial survival.
  • SPI2's interference with iNOS is essential for Salmonella virulence and pathogenesis.

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