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New aspects of RpoE in uropathogenic Proteus mirabilis

Ming-Che Liu1, Kuan-Ting Kuo2, Hsiung-Fei Chien3

  • 1Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.

Infection and Immunity
|December 31, 2014
PubMed

Insights

Sigma factor E (RpoE) in Proteus mirabilis is crucial for urinary tract infection (UTI) pathogenesis. Loss of RpoE impairs virulence but enhances swarming motility, suggesting RpoE regulates host-pathogen interactions and environmental sensing during UTIs.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Proteus mirabilis frequently causes complicated urinary tract infections (UTIs).
  • Mechanisms of P. mirabilis virulence in UTIs remain incompletely understood.
  • The role of extracytoplasmic stress response regulators in P. mirabilis pathogenesis is largely unknown.

Purpose of the Study:

  • To investigate the role of sigma factor E (RpoE) in P. mirabilis virulence and host-pathogen interactions during UTIs.
  • To elucidate the regulatory mechanisms by which RpoE influences P. mirabilis fitness in the urinary tract environment.

Main Methods:

  • Generating a rpoE mutant of P. mirabilis.
  • Assessing bacterial virulence factors including fimbria expression, macrophage survival, and cell invasion.
  • Evaluating P. mirabilis colonization and host immune responses in a murine UTI model.
  • Utilizing real-time reverse transcription-PCR to quantify gene expression.
  • Employing reporter assays to study RpoE activation by urine components.

Main Results:

  • Loss of RpoE significantly decreased P. mirabilis virulence, including fimbria expression, macrophage survival, invasion, and colonization.
  • RpoE deficiency led to increased swarming motility and elevated interleukin-8 (IL-8) expression in urothelial cells.
  • RpoE regulates MR/P fimbriae expression via the recombinase gene mrpI.
  • Urothelial cells exposed to lipopolysaccharides from the rpoE mutant showed significantly induced IL-8 mRNA.
  • Infection with the rpoE mutant resulted in increased immune cell infiltration and impaired colonization in mice.
  • Urea and polymyxin B were found to induce rpoE expression, indicating RpoE activation in the urinary tract.

Conclusions:

  • RpoE is essential for P. mirabilis virulence and fitness in the urinary tract.
  • RpoE mediates the expression of key virulence factors, including MR/P fimbriae, contributing to host immune evasion.
  • RpoE acts as a critical sensor of the urinary tract environment, enabling P. mirabilis adaptation and UTI establishment.

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