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Tissue-binding affinity of Proteus mirabilis fimbriae in the human urinary tract
T Sareneva1, H Holthöfer, T K Korhonen
1Department of General Microbiology, University of Helsinki, Finland.
Abstract:
Binding characteristics of the two major fimbrial hemagglutinin types of uropathogenic Proteus mirabilis were determined in frozen sections of human kidney and in exfoliated uroepithelial cells. P. mirabilis 3087, which expresses the MR/P fimbriae, adhered avidly to the tubular epithelial cells of the kidney and also to the epithelial cells of urinary sediment. No adhesion to glomerular or peritubular elements of the kidney was detected. Indirect immunogold silver staining also showed that the purified MR/P fimbriae recognized the same kidney domains. Adhesion of strain 3087 to uroepithelial cells was completely inhibited by Fab fragments of antibodies against the purified MR/P fimbriae. A completely different tissue-binding pattern was exhibited by the MR/K fimbriae of P. mirabilis 2456. In the kidney, the MR/K fimbriae bound strongly to the Bowman's capsule of the glomeruli and to the tubular basement membranes. A weak binding to glomerular mesangium and tubular epithelial cells was also seen. Strain 2456 did not adhere to epithelial cells of urinary sediment. Analysis of normal human urine showed that it contains low-molecular-weight molecules capable of inhibiting the binding of the MR/P fimbriae; no urinary inhibitors could be detected for the MR/K fimbriae. Poor in vivo binding capacity to intact human uroepithelial cells may be an important factor in explaining the relatively low pathogenicity of P. mirabilis in healthy hosts.
Insights
Uropathogenic Proteus mirabilis fimbriae show distinct kidney and urinary tract binding. MR/P fimbriae target uroepithelial cells, while MR/K fimbriae bind to glomerular structures, influencing pathogenicity.
Area of Science:
- Microbiology
- Urology
- Immunology
Background:
- Uropathogenic Proteus mirabilis utilizes fimbriae for host tissue adhesion.
- Two major fimbrial hemagglutinin types, MR/P and MR/K, are expressed by P. mirabilis.
- Understanding fimbrial binding is crucial for elucidating P. mirabilis pathogenicity.
Purpose of the Study:
- To characterize the binding specificities of MR/P and MR/K fimbriae of P. mirabilis.
- To investigate the interaction of these fimbriae with human kidney and uroepithelial cells.
- To explore the role of urinary factors in modulating fimbrial adhesion.
Main Methods:
- Frozen sections of human kidney and exfoliated uroepithelial cells were used as targets.
- Indirect immunogold silver staining was employed to visualize fimbrial binding.
- Fab fragments of antibodies were used to inhibit MR/P fimbrial adhesion.
- Analysis of human urine for potential inhibitors of fimbrial binding.
Main Results:
- MR/P fimbriae avidly adhered to kidney tubular epithelial cells and urinary sediment cells, but not glomerular elements.
- MR/K fimbriae bound strongly to glomerular Bowman's capsule and tubular basement membranes, with weak binding to mesangium and tubular cells.
- MR/P fimbrial adhesion was inhibited by specific antibodies, confirming target recognition.
- Normal human urine inhibited MR/P fimbrial binding, but not MR/K fimbrial binding.
Conclusions:
- MR/P and MR/K fimbriae exhibit distinct tissue tropisms within the human urinary tract.
- The differential binding patterns may contribute to the varying roles of these fimbriae in P. mirabilis infections.
- The presence of urinary inhibitors for MR/P fimbriae could impact P. mirabilis colonization and pathogenicity in the urinary tract.