Hemolysin from Shiga toxin-negative Escherichia coli O26 strains injures microvascular endothelium

Aldick T, Bielaszewska M, Zhang W, Brockmeyer J, Schmidt H, Friedrich AW, Kim KS, Schmidt MA, Karch H

Abstract

We identified Shiga toxin gene (stx)-negative Escherichia coli 026:H11 and 026:NM (nonmotile) strains as the only pathogens in the stools of five patients with hemolytic-uremic syndrome (HUS). Because the absence of stx in E. coli associated with HUS is unusual, we examined the strains for potential virulence factors and interactions with microvascular endothelial cells which are the major targets affected during HUS. All five isolates possessed the enterohemorrhagic E. coli (EHEC)-hlyA gene encoding EHEC hemolysin (EHEC-Hly), expressed the enterohemolytic phenotype, and were cytotoxic, in dose- and time-dependent manners, to human brain microvascular endothelial cells (HBMECs). Significantly reduced cytotoxicity in an EHEC-Hly-negative spontaneous derivative of one of these strains, and a dose- and time-dependent cytotoxicity of recombinant E. coli 026 EHEC-Hly to HBMECs, suggest that the endothelial cytotoxicity of these strains was mediated by EHEC-Hly. The toxicity of EHEC-Hly to microvascular endothelial cells plausibly contributes to the virulence of the stx-negative E. coli 026 strains and to the pathogenesis of HUS. (c) 2006 Elsevier Masson SAS. All rights reserved.