UREASE--MOLECULAR STUDIES & ROLE IN PATHOGENESIS

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Urinary tract infection (UTI) is common in both the community and hospital setting. In the female population alone, the rate of infection is approximately 6% per year in the United States. UTI is the most prevalent form of nosocomial infection and the most prevalent cause of gram negative bacteremia with its attendant high mortality rate due to sepsis. There are a number of bacterial species associated with UTI, the majority of which are members of the Enterobacteriaceae family. These urinary tract pathogens share the ability to express at least one of a number of virulence factors that include adhesions, hemolysins, aerobactin, and urease; the latter of these is the focus of this study. Urease produces a number of effects in the urinary tract, including the formation of renal and bladder stones, usually composed of struvite, a magnesium ammonium phosphate precipitate. Urease producing organisms are commonly associated with hospital acquired UTI, and chronically catheterized individuals can have urinary tracts colonized with more than one ureolytic bacterial pathogen. Klebsiella pneumomiae is often associated with both community acquired and hospital acquired UTI. The purpose of this study is twofold: i) to determine if urease activity enhances the virulence of K. pneumoniae in a UTI and ii) to study at the molecular and genetic level the urease locus of a uropathogenic K. pneumoniae isolate. This work should help elucidate the role of urease in UTI and define an uncharacterized K. pneumoniae trait. In addition to urinary tract pathogens, urease has been implicated as a virulence factor in other bacterial pathogens such as Campylobacter pylori and Ureaplasma urealyticum. An understanding of K. pneumoniae urease and the K. pneumoniae urease genes will provide a basis for comparative study of urease and the urease loci of these other strains.