OmpR and acid regulation of Escherichia coli fim genes

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DESCRIPTION (provided by applicant): Uropathogenic Escherichia coli (UPEC) are the leading cause of urinary tract infections in the United States, resulting in millions of cases each year. Attachment to epithelial cells is a vital first step in UPEC induced urinary tract infections. Type 1 pili mediate this binding, and animal studies have shown a critical role for this pilus type in human bladder infections. Expression of type 1 pili is affected by phase variation whereby cells can switch between piliated and nonpiliated states. Nine fim genes are involved in type 1 pilus expression, including the fimA gene that encodes the structural subunits and site-specific recombinases that affect phase variation encoded by fimB and fimE. Several environmental factors influence regulation of these fim genes, but little is known about the environmental cues regulating fim gene expression in UPEC living in the human urinary tract. Because UPEC cause many urinary tract infections each year, this grant proposes to answer how OmpR and acid tolerance gene proteins may be regulating type 1 pilus expression in UPEC by performing DNase footprinting, PCRs, Western blots, and reporter assays to elucidate fimA, fimB, and fimE expression. Moreover, this proposal will examine for the first time the regulation of these three genes in UPEC cells inoculated into murine urinary tracts using a reporter system. How the fim genes are regulated will be uncovered, which could be useful for future prevention strategies that use dietary changes to change the internal environment of the human urinary tract and prevent the UPEC from binding. This research will help us understand the regulation of type 1 pili fim genes in uropathogenic Escherichia coli growing in human urinary tracts. By understanding how the fim genes are regulated, we may be able to treat urinary tract infections in the future through dietary changes or drugs that affect the regulatory cascade that leads to type 1 pilus expression.