Regulation of Expression of Uropathogenic Escherichia coli Nonfimbrial Adhesin TosA by PapB Homolog TosR in Conjunction with H-NS and Lrp
Urinary tract infections (UTIs) are a major burden to human health. The overwhelming majority of UTIs are caused by uropathogenicEscherichia coli(UPEC) strains. Unlike some pathogens, UPEC strains do not have a fixed core set of virulence and fitness factors but do have a variety of adhesins and regulatory pathways. One such UPEC adhesin is the nonfimbrial adhesin TosA, which mediates adherence to the epithelium of the upper urinary tract. Thetosoperon is AT rich, resides on pathogenicity islandaspV, and is not expressed under laboratory conditions. Because of this, we hypothesized thattosAexpression is silenced by H-NS. Lrp, based on its prominent function in the regulation of other adhesins, is also hypothesized to contribute totosoperon regulation. Using a variety ofin vitrotechniques, we mapped both thetosoperon promoter and TosR binding sites. We have now identified TosR as a dual regulator of thetosoperon, which could control thetosoperon in association with H-NS and Lrp. H-NS is a negative regulator of thetosoperon, and Lrp positively regulates thetosoperon. Exogenous leucine also inhibits Lrp-mediatedtosoperon positive regulation. In addition, TosR binds to thepapoperon, which encodes another important UPEC adhesin, P fimbria. Induction of TosR synthesis reduces production of P fimbria. These studies advance our knowledge of regulation of adhesin expression associated with uropathogen colonization of a host.