Urinary tract infections (UTI) are among the most common human infections, and may have serious health sequelae. Most UTI are caused by members of the bacterial family Enterobacteriaceae. Both epidemiological data and studies with animal models have implicated the important role of specific bacterial adhesins (pili or fimbriae) in the colonization of the UT by bacteria normally found in the human large bowel. The object of this research proposal is to characterize and compare, using modern genetic techniques, the DNA sequences encoding these bacterial adhesins with the ultimate goal of developing methods to prevent bacterial adherence to UT epithelial cells. More specifically, the methods of recombinant DNA technology will be used to (1) isolate and identify the genes coding for mannose-resistant adhesins non-homologous to the P-pili of Escherichia coli (which allow E. coli to bind avidly to uroepithelium); and (2) isolate and identify the gene(s) conferring adherence to uroepithelium from Proteus mirabilis, a common cause of hospital acquired UTI. Extensive DNA hybridization experiments will be carried out to compare the gene for P pilin of a well studied uropathogenic E. coli to other UTI isolates. It is hoped that these experiments may identify common genetic sequences that might be explored as targets for the development of vaccines or for specific chemical inhibitors to prevent the expression or function of bacterial adhesins.
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