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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
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Virulence regulation in Citrobacter rodentium: the art of timing

Ji Yang1, Marija Tauschek, Emily Hart

  • 1Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010, Australia.

Microbial Biotechnology
|January 25, 2011
PubMed

Insights

Citrobacter rodentium uses a regulatory protein, RegA, to control virulence. RegA activates colonization factors and represses housekeeping genes in response to gut bicarbonate signals.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Citrobacter rodentium is a mouse model pathogen causing attaching and effacing lesions, similar to human enteropathogenic E. coli.
  • Virulence relies on the locus for enterocyte effacement (LEE) and a regulatory network involving LEE-encoded proteins (Ler, GrlA, GrlR).
  • Non-LEE encoded transcription factors also modulate virulence gene expression in response to environmental cues.

Purpose of the Study:

  • To investigate the role of the non-LEE encoded regulatory protein RegA in C. rodentium intestinal colonization.
  • To elucidate the function of RegA in regulating virulence-associated and housekeeping genes.
  • To determine the environmental signals that regulate RegA activity.

Main Methods:

  • Identification and characterization of the AraC-like regulatory protein RegA.
  • Analysis of RegA's impact on the transcription of horizontally acquired operons and housekeeping genes.
  • Investigation of the role of bicarbonate as a gut-specific environmental signal for RegA.

Main Results:

  • RegA is crucial for C. rodentium intestinal colonization.
  • RegA activates transcription of operons encoding virulence factors (e.g., autotransporters, fimbriae, dispersin).
  • RegA represses the transcription of housekeeping genes and requires bicarbonate to function.

Conclusions:

  • RegA acts as a key regulator in C. rodentium, linking environmental signals to virulence.
  • Bicarbonate sensing by RegA orchestrates a shift from cellular functions to colonization and virulence factor production.
  • RegA represents a novel target for understanding and potentially controlling enteric bacterial infections.

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