P fimbriae of uropathogenic Escherichia coli as multifunctional adherence organelles
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B Westerlund1, I Van Die, W Hoekstra
1Department of General Microbiology, University of Helsinki, Finland.
Abstract:
P fimbriae are the major single virulence factor of uropathogenic Escherichia coli strains. Recent analyses have shown that P fimbriae possess two distinct binding specificities mediated by different fimbrial subunits. P fimbriae bind to Gal alpha (1-4)Gal-containing globoseries of glycolipids of epithelial cells; this binding is mediated by the lectin-like minor protein G of the filament. In vitro mapping of the human urinary tract for binding sites of P fimbriae has revealed that they bind in a Gal alpha (1-4)Gal-inhibitable manner to epithelia of kidney and bladder. On the other hand, P fimbriae bind to immobilized fibronectin and its amino- and carboxyterminal fragments; this binding is dependent on the E and the F minor proteins of the P-fimbrial filament and seems to be based on a protein-protein interaction. The P fimbriae-fibronectin interaction has been demonstrated also on frozen sections of kidney. P fimbriae thus possess two tissue-adherence properties: one specific for epithelial glycoconjugates and the other for fibronectin of subepithelial extracellular matrices. P-fimbrial binding to epithelial glycoconjugates seems to be important in determining the host tropism and enabling the ascent of E. coli urinary tract infections. Binding to fibronectin may be important in secondary phases of the infection, e.g. after epithelial injury.
Insights
P fimbriae, a key virulence factor in E. coli, exhibit dual binding capabilities. They adhere to epithelial cell glycolipids and subepithelial fibronectin, influencing urinary tract infection progression.
Area of Science:
- Microbiology
- Molecular Biology
- Urology
Background:
- Uropathogenic Escherichia coli (UPEC) are a significant cause of urinary tract infections.
- P fimbriae are a primary virulence factor in UPEC, mediating adherence to host tissues.
- Understanding P fimbriae's binding mechanisms is crucial for combating UPEC infections.
Purpose of the Study:
- To elucidate the dual tissue-adherence properties of P fimbriae.
- To differentiate the roles of P fimbriae binding to epithelial cells versus extracellular matrix components.
- To investigate the specific subunits involved in P fimbriae-host interactions.
Main Methods:
- In vitro binding assays using human urinary tract epithelia.
- Analysis of P fimbriae binding to immobilized fibronectin and its fragments.
- Mapping of binding sites and inhibition studies using Gal alpha (1-4)Gal.
- Examination of P fimbriae-fibronectin interactions on kidney tissue sections.
Main Results:
- P fimbriae exhibit two distinct binding specificities mediated by different fimbrial subunits.
- Binding to epithelial Gal alpha (1-4)Gal-containing glycolipids is mediated by minor protein G.
- Binding to fibronectin involves minor proteins E and F, suggesting protein-protein interaction.
- P fimbriae bind to kidney and bladder epithelia in a Gal alpha (1-4)Gal-inhibitable manner.
- P fimbriae-fibronectin interactions are observed on kidney tissue.
Conclusions:
- P fimbriae possess dual tissue-adherence mechanisms: one targeting epithelial glycoconjugates and another targeting subepithelial fibronectin.
- Glycoconjugate binding is vital for UPEC host tropism and ascending infections.
- Fibronectin binding may play a role in later stages of infection, such as post-epithelial injury.