Hemolysin from Shiga toxin-negative Escherichia coli O26 strains injures microvascular endothelium.
We identified Shiga toxin gene (stx)-negative Escherichia coli O26:H11 and O26: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 O26 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 O26 strains and to the pathogenesis of HUS.
Aldick
Thomas
T
Institute of Hygiene and the National Consulting Laboratory on Hemolytic Uremic Syndrome, University of Münster, Robert Koch Str. 41, 48149 Münster, Germany.
Bielaszewska
Martina
M
Zhang
Wenlan
W
Brockmeyer
Jens
J
Schmidt
Herbert
H
Friedrich
Alexander W
AW
Kim
Kwang S
KS
Schmidt
M Alexander
MA
Karch
Helge
H
D001422:Bacterial Adhesion; D001921:Brain / Q000166:cytology; D018938:Caco-2 Cells; D002460:Cell Line; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000382:microbiology / Q000473:pathology*; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology*; D006801:Humans; D007223:Infant; D008833:Microcirculation / Q000473:pathology; D022621:Shiga Toxin / Q000235:genetics / Q000378:metabolism*
D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; D022621:Shiga Toxin