Uropathogenic and diarrheal Escherichia coli strains expressing adhesins of the Dr family bind to decayaccelerating factor, invade epithelial cells, preferentially infect children and pregnant women, and may be associated with chronic or recurrent infections. Thus far, no fimbrial domain(s) that facilitates cell invasion has been identified. We used alanine scanning mutagenesis to replace selected amino acids in hydrophilic domain II of the structural fimbrial subunit DraE and evaluated recombinant mutant DraE for attachment, invasion, and intracellular compartmentalization. The mutation of amino acids V28, T31, G33, Q34, T36, and P40 of DraE reduced or abolished HeLa cell invasion but did not affect attachment. Electron micrographs showed a stepwise entry and fusion of vacuoles containing Escherichia coli mutants T36A and Q34A or corresponding beads with lysosomes, whereas vacuoles with wild-type Dr adhesin showed no fusion. Mutants T31A and Q34A, which were deficient in invasion, appeared to display a reduced capacity for clustering decay-accelerating factor. Our findings suggest that hydrophilic domain II may be involved in cell entry. These data are consistent with the interpretation that in HeLa cells the binding and invasion phenotypes of Dr fimbriae may be separated.

The protective effect of estrogen replacement on ascending urinary-tract infection (UTI) is controversial. We designed a study using an experimental model of UTI in which surgically menopausal mice were supplemented with estrogen and the susceptibility to UTI was evaluated after experimental Escherichia coli infection. The mean rate of E. coli infection in the group not treated with estrogen was 2 x 10(4) cfu/g of renal tissue, compared with 9 x 10(8) cfu/g (P<.001) in the estrogen-treated group. Surprisingly, despite the hypothesis that estrogen would protect mice from infection, estrogen treatment significantly increased the susceptibility of the mice to ascending UTI.