Cytolethality of hemolytic Escherichia coli to primary human renal proximal tubular cell cultures obtained from different donors

Abstract

Objectives In earlier experiments, we confirmed epidemiologic studies demonstrating the prominence in acute pyelonephritis of Escherichia coli expressing P fimbriae and hemolysin, produced the disease with pyelonephritogenic strains in an an imal model, and developed in vitro assays using human renal proximal tubular cells that demonstrated bacterial adherence by P fimbriae and killing of the renal cells by he molysin. In the present series of experiments, we sought to determine whether P fimbriated hemolytic E coli killed human renal proximal tubular epithelial cells obtained from different human donors. Methods Human renal proximal tubular cells, putative target cells for bacteria causing acute pyelonephritis, were cultured from 9 donors and cell death was measured by two methods. Results We showed that the E coli strain was significantly more cytolethal for renal cells of all donors than its hemolysin-negative mutant. Conclusions This work suggests that the pathogenesis of acute pyelonephritis by P-fimbriated hemolytic E coli, characteristics of the causative organism in about 50% of human cases, may be at least in part through killing of human renal epithelial cells by hemolysin.