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Integrin-mediated host cell invasion by type 1-piliated uropathogenic Escherichia coli
Danelle S Eto1, Tiffani A Jones, Jamie L Sundsbak
1Division of Cell Biology and Immunology, Pathology Department, University of Utah, Salt Lake City, Utah, United States of America.
Plos Pathogens
|July 17, 2007
Summary
Uropathogenic Escherichia coli (UPEC) uses type 1 pili to invade bladder cells. Researchers identified beta1 and alpha3 integrins as key receptors, revealing new targets for treating urinary tract infections.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Uropathogenic Escherichia coli (UPEC) causes urinary tract infections using type 1 pili for attachment and invasion.
- Previous research identified potential receptors for UPEC, but none were conclusively shown to mediate bacterial entry into host cells.
Purpose of the Study:
- To identify key host cell receptors for UPEC type 1 pili that facilitate bacterial invasion.
- To elucidate the molecular mechanisms by which UPEC invades bladder urothelial cells.
Main Methods:
- Overlay assays with purified FimH (type 1 pilus adhesin) and mass spectrometry to identify host receptors.
- Bladder cell culture systems to observe bacterial-receptor interactions and invasion.
- Inhibition studies using integrin-specific antibodies and gene disruption.
- Analysis of integrin signaling pathways involving kinases and cytoskeletal rearrangements.
Main Results:
- Beta1 and alpha3 integrins were identified as key host receptors for UPEC, recognized by the FimH adhesin.
- These integrins co-localize with invading bacteria and F-actin in bladder cells.
- Inhibition of beta1 and alpha3 integrins, or disruption of the beta1 integrin gene, reduced UPEC invasion.
- Integrin signaling pathways, including focal adhesion and Src family kinases, are crucial for FimH-dependent invasion.
Conclusions:
- Beta1 and alpha3 integrins are functionally important receptors for UPEC type 1 pili.
- These integrins mediate bacterial entry into host bladder cells via FimH recognition.
- Understanding this interaction provides insights into UPEC pathogenesis and potential therapeutic strategies.
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