Role of type 1 fimbrial mutations in the pathogenesis of pandemic E. coli

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ABSTRACT Adhesion is an essential trait for the pathogenesis of urinary tract infections and intestinal colonization by E. coli and mannose-specific type 1 fimbriae (T1F) is the most critical adhesive factor. Our goal is to understand how some of the unique features in T1F of the pandemic uropathogenic clonal group, ST131-H30, are adaptive for this sub-clone's urovirulence and intestinal fitness. We will concentrate on the structure-functional analysis of the mannose-binding adhesive subunit of the fimbriae, FimH, and the regulatory mechanism of fimbrial expression that are specific to ST131-H30. We will characterize in great detail the functional properties of the fimbrial adhesin, FimH, by comparing its ability to mediate adhesion under various flow and inhibitory conditions. We also will determine the functional significance of genetic insertion that inactivated the gene coding for positive regulator of T1F, FimB. We will attempt to understand in what way this mutation affected expression of T1F itself as well as other genes across the genome and the E. coli’s virulence and colonization properties. Finally, we will use animal studies to determine the adaptive significance of the T1F and its variants in ST131-H30.