Induction and Evasion of Host Defenses by Type 1-Piliated Uropathogenic Escherichia coli

• DOI: 10.1126/science.282.5393.1494
• Publication Date: 2002-07-27T09:50:14Z
• Authors: Matthew A. Mulvey; Yolanda S. Lopez-...; Carole L. Wilson; Robyn Roth; William C. Parks; John Heuser; Scott J. Hultgren
• Keywords: 0301 basic medicine; Apoptosis; DNA Fragmentation; Cysteine Proteinase Inhibitors; Bacterial Adhesion; Amino Acid Chloromethyl Ketones; Mice; 03 medical and health sciences; Cystitis; Escherichia coli; In Situ Nick-End Labeling; Animals; Adhesins, Bacterial; Escherichia coli Infections; Adhesins, Escherichia coli; 0303 health sciences; Membrane Glycoproteins; Caspase Inhibitors; 3. Good health; Mice, Inbred C57BL; Caspases; Fimbriae, Bacterial; Female; Fimbriae Proteins

Virtually all uropathogenic strains of Escherichia coli encode filamentous surface adhesive organelles called type 1 pili. High-resolution electron microscopy of infected mouse bladders revealed that type 1 pilus tips interacted directly with the lumenal surface of the bladder, which is embedded with hexagonal arrays of integral membrane glycoproteins known as uroplakins. Attached pili were shortened and facilitated intimate contact of the bacteria with the uroplakin-coated host cells. Bacterial attachment resulted in exfoliation of host bladder epithelial cells as part of an innate host defense system. Exfoliation occurred through a rapid apoptosis-like mechanism involving caspase activation and host DNA fragmentation. Bacteria resisted clearance in the face of host defenses within the bladder by invading into the epithelium.