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Transcriptome of Proteus mirabilis in the murine urinary tract: virulence and nitrogen assimilation gene expression

Melanie M Pearson1, Alejandra Yep, Sara N Smith

  • 1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

Infection and Immunity
|April 21, 2011
PubMed

Insights

Proteus mirabilis upregulates key virulence genes like urease and fimbriae during urinary tract infections in mice. Glutamate dehydrogenase (gdhA) plays a crucial role in its pathogenesis and nutrient utilization.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Proteus mirabilis is a significant cause of complicated urinary tract infections (cUTIs).
  • Understanding P. mirabilis gene expression during infection is crucial for developing targeted therapies.

Purpose of the Study:

  • To analyze the in vivo gene expression profile of P. mirabilis during a mouse model of urinary tract infection.
  • To investigate the role of ammonia assimilation pathways, specifically glutamate dehydrogenase (gdhA), in P. mirabilis pathogenesis.

Main Methods:

  • Transcriptional analysis using microarrays on P. mirabilis RNA isolated from infected mouse urine at multiple time points.
  • Construction and characterization of a gdhA mutant in P. mirabilis.
  • Growth assays in minimal media and fitness studies in a mouse UTI model.

Main Results:

  • In vivo, P. mirabilis upregulated genes for mannose-resistant Proteus-like (MR/P) fimbriae, urease, iron uptake, and central metabolism (TCA cycle).
  • Flagellar genes were downregulated in vivo.
  • Ammonia assimilation gene glnA was repressed, while glutamate dehydrogenase gene gdhA was upregulated in vivo.
  • A gdhA mutant exhibited growth defects in minimal media with citrate and a significant fitness defect in the mouse UTI model.

Conclusions:

  • P. mirabilis employs distinct gene expression strategies in vivo compared to in vitro conditions.
  • Glutamate dehydrogenase (gdhA) is essential for P. mirabilis's ability to utilize citrate and contributes significantly to its pathogenic potential in the urinary tract.
  • Unlike E. coli, P. mirabilis appears to utilize gdhA for monitoring carbon-nitrogen balance during infection.

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