(229i) Measuring Adhesion Between Uropathogenic E. coli and Bladder-Epithelial Cells

Bacterial adhesion to host cells is often a first step in the infection process. For example, uropathogenic Escherichia coli, the major causative agent of urinary tract infection, bind to host bladder-epithelial cells and initiate cell invasion. This triggers a subsequent pathogenic cascade characterized by recurrent infection. There is currently growing interest in developing new antimicrobials that, instead of targeting bacterial survival and placing high selective pressure for drug-resistant mutations, target mechanisms promoting infection such as binding to host cells. This new therapeutic strategy requires a detailed understanding of bacterial adhesion. To address this issue, we used in vitro methods to examine the factors that contribute to the adhesion of E. coli to the bladder epithelium, including both traditional tissue-culture based assays and novel mechanical measurements. Specifically, we used an adapted live-cell rheometer to make direct physical measurements of bacterial adhesion to a monolayer of bladder epithelial cells. This method allowed us to quantify the extent to which extracellular bacterial components affect adhesion. Our results indicate that an extracellular amyloid fiber commonly produced by uropathogenic stains of E. coli, termed curli, increase adhesion to bladder epithelial cells and may therefore play a role in the infection process. In the future, we plan to use these techniques to assess the effectiveness of various small molecules in blocking bacterial binding to host cells.