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

• Published in: Urology (Ridgewood, N.J.) N.J.), 1995-04, Vol.45 (4), p.706-710
• Main Authors: Warren, John W., Mobley, Harry L.T., Hebel, John R., Trifillis, Anna L.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Survival; Cells, Cultured; Escherichia coli - metabolism; Fimbriae, Bacterial; Hemolysin Proteins - biosynthesis; Hemolysin Proteins - physiology; Humans; Infant; Kidney Tubules, Proximal - cytology; L-Lactate Dehydrogenase - metabolism; Medical sciences; Nephrology. Urinary tract diseases; Neutral Red - pharmacology; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(99)80071-5

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. 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. We showed that the E coli strain was significantly more cytolethal for renal cells of all donors than its hemolysin-negative mutant. 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.