Urinary tract infections (UTIs) are a major cause of morbidity in women and the aged. Over 80% of UTIs are caused by E. coli and most of these strains express the type 1 fimbriae. Since these fimbriae are also expressed on nonpathogenic E. coli their role in virulence is unclear. However, the investigators have detected considerable heterogeniety in binding among different type 1 fimbriae which could determine to which strains are virulent and the nature of the inflammatory response in the host. MC are prominent inflammatory cells in the bladder and are found in close proximity to the bladder epithelial cells (BEC). they have also found that certain type 1 fimbriated strains of E. coli can gain access into mast cells (MC) and then subsequently escape without loss of bacterial viability. The trafficking process is triggered by the specific binding of type 1 fimbriae to CD48 on the MC membrane. Interestingly, BEC were found to modulate the trafficking of E. coli in MC as a reservoir may in release of stem cell factor (SCF). This capacity of type 1 fimbriated E. coli to utilize MC as a reservoir may in part explain recurrent UTIs. To extend their observations they plan to (i), determine if and how type 1 fimbriae from uropathogenic E. coli isolates display distinct binding traits compared to commensal isolates (ii), determine whether different E. coli type 1 fimbriae bind separate receptors on the host cells and if there is diversity in the host cell's responses (iii), elucidate the molecular mechanisms of CD48 mediated trafficking of type 1 fimbriated E. coli in MC and (iv), elucidate how SCF modulates MC carriage of bacteria. The information derived from these studies could promote the development of novel strategies for the prevention and management of E. coli -induced UTIs including recurrences. In the age of increasing antibiotic resistance in bacteria and where the population of the aged and immunocompromised individuals continues to grow, these studies could prove to be extremely valuable.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
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Bacteriology and Mycology Subcommittee 2 (BM)
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Mullins, Christopher V
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Duke University
Schools of Medicine
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