Internalization of extraintestinal Escherichia coli O18 strains by epithelial cells is modulated by EGF, insulin, and effectors of transmembrane signal transduction

Adhesion to and internalization into host cells is an essential step in the pathogenesis of various bacterial infections. Here we investigated the eff ects of growth factors on the internalization of Escherichia coli O18 strai ns isolated from patients with urinary tract infection (UTI) by human epith elial cells. A dramatic increase in the uptake of Escherichia coil was obse rved after treatment of epithelial cells with epidermal growth factor (EGF) and to a lower extent with insulin. EGF-dependent internalization can be s uppressed by tyrosine kinase inhibitors suggesting an involvement of the re ceptor tyrosine kinases in the regulation of the endocytotic process. Inhib itors of phospholipase A(2), lipoxygenase, and cyclooxygenase significantly decreased internalization of bacteria induced by EGF. Finally, the specifi c inhibitor of PI 3-kinases Wortmannin was shown to suppress completely the EGF-independent internalization. The data of this analysis indicate the involvement of several signaling pat hs in bacterial internalization of uropathogenic Escherichia coil O18 strai ns and contribute to the comprehension of the pathogenesis of recurrent UTI .