| Urinary tract infections encompass a broad range of infectious conditions, symptoms and causative agents, and are influenced by an array of host and agent factors. Escherichia coli is by far the most common cause of urinary tract infections (UTI) and accounts for 80% of ambulatory UTI. Uropathogenic E. coli (UPEC) possess characteristics that enable them to cause infections of the urinary tract, and differentiate them from the normal flora. These include adhesins, toxins, a capsule, siderophores and an outer membrane protease.;In this dissertation I describe the results of three related projects advancing molecular epidemiology of UTI: (1) We determined that diabetic women often had long term, asymptomatic carriage of a single E. coli isolate. Women who were treated carried a single strain for a shorter time as compared to women who were not treated. The rates of known virulence characteristics in ASB diabetic women was similar to that found in non-pathogenic fecal isolates. (2) We identified a novel variant of a newly described gene cluster auf, that we named aasp (adhesin associated with sexual partnership) using genomic subtraction, and found that the general adhesin type was associated with sharing between heterosexual partners. UPEC are known to be shared between sex partners, and it appears that this new adhesin may facilitate transmission. In addition, a 273 bp open reading frame encoding a 11 kDa protein that is 38% similar to the transcriptional regulatory protein PapB found in the P pilus fimbrial gene system, which was designated, PapB homologue regulator (pbhr) was also identified. pbhr does not localize near other fimbrial genes but is strongly associated epidemiologically to aasp, suggesting a functional linkage. (3) Finally, the distributions of the two novel variants of adhesin were determined in a collection of E. coli isolates from women with a first UTI, second UTI, infants with pyelonephritis and rectal E. coli without UTI, and auf was found to occur far more frequently in all collections, and was strongly associated with isolates from women with UTI. |
