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Virulence determinants of uropathogenic Escherichia coli and Proteus mirabilis
H L Mobley1, M D Island, G Massad
1Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore.
Abstract:
The urinary tract is among the most common sites of bacterial infection and E. coli is by far the most common infecting agent. In patients with urinary catheters in place or structural abnormalities of the urinary tract, Proteus mirabilis is also a frequent isolate. To study virulence of these bacterial species, we have isolated the genes that encode putative virulence factors, constructed specific mutations within these genes, introduced the mutation back into the wild type strain by allelic exchange, and analyzed these mutants for virulence in appropriate in vitro and in vivo models. Specific virulence markers have been identified for strains that cause urinary tract infection. For E. coli, these include P fimbriae, S fimbriae, hemolysin, aerobactin, serum resistance, and a small group of O-serotypes. Redundant virulence factors must be present in these organisms as mutation of the most clearly identified epidemiological marker, P fimbriae, does not result in attenuation of a virulent strain. For P. mirabilis, urease appears to contribute most significantly to virulence. Fimbriae play a significant but more subtle role in colonization. Hemolysin, although potently cytotoxic to renal cells in vitro, does not appear to contribute significantly to the pathogenesis of ascending urinary tract infection. We can conclude that the pathogenesis of urinary tract infection and acute pyelonephritis caused by uropathogenic E. coli and P. mirabilis are multifactorial, as mutation of single genes rarely causes significant attenuation of virulence.
Insights
Urinary tract infections are common, often caused by E. coli and Proteus mirabilis. Virulence factors are multifactorial, meaning single gene mutations rarely reduce bacterial infection severity.
Area of Science:
- Microbiology
- Infectious Diseases
- Urology
Background:
- Urinary tract infections (UTIs) are highly prevalent, with Escherichia coli (E. coli) as the primary causative agent.
- Proteus mirabilis is also a significant pathogen, particularly in patients with urinary catheters or structural abnormalities.
Purpose of the Study:
- To identify and analyze bacterial virulence factors contributing to UTIs.
- To understand the multifactorial nature of pathogenesis in E. coli and P. mirabilis UTIs.
Main Methods:
- Isolation of genes encoding putative virulence factors.
- Construction of specific gene mutations via allelic exchange.
- Analysis of mutant strains' virulence in vitro and in vivo models.
Main Results:
- For E. coli, virulence markers include P fimbriae, S fimbriae, hemolysin, aerobactin, serum resistance, and specific O-serotypes.
- P fimbriae mutation did not attenuate E. coli virulence, suggesting redundant factors.
- For P. mirabilis, urease is a major virulence factor, while fimbriae play a role in colonization.
- Hemolysin showed in vitro cytotoxicity but minimal in vivo UTI pathogenesis contribution.
Conclusions:
- UTI and pyelonephritis pathogenesis by E. coli and P. mirabilis is multifactorial.
- Single gene mutations typically do not significantly attenuate virulence, highlighting the complexity of these infections.