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

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 animal 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 hemolysin. 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.