TY - JOUR
T1 - Hemolysin from Shiga toxin-negative Escherichia coli O26 strains injures microvascular endothelium
AU - Aldick, Thomas
AU - Bielaszewska, Martina
AU - Zhang, Wenlan
AU - Brockmeyer, Jens
AU - Schmidt, Herbert
AU - Friedrich, Alexander W.
AU - Kim, Kwang S.
AU - Schmidt, M. Alexander
AU - Karch, Helge
N1 - Funding Information:
This study was supported by the Deutsche Forschungsgemeinschaft (DFG) program “Infections of the endothelium” SPP 1130, grant KA 717/4-2, by a grant from the Interdisciplinary Center of Clinical Research Münster (IZKF, Project no. Ka2/061/04), by DFG Sonderforschungsbereich (SFB) grants SFB293 B5 and SFB629 B2, by a grant from the Bundesministerium für Bildung und Forschung (BMBF) Project Network of Competence Pathogenomics Alliance “Functional genomic research on enterohemorrhagic, enteropathogenic and enteroaggregative Escherichia coli” (BD number 119523/207800), and by a grant from the EU Network of Excellence EuroPathoGenomic (number LSHB-CT-2005-512061).
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Adherence
KW - Cytotoxicity
KW - Enterohemorrhagic E. coli hemolysin
KW - Escherichia coli O26
KW - Hemolytic-Uremic syndrome
KW - Microvascular endothelial cells
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U2 - 10.1016/j.micinf.2006.12.001
DO - 10.1016/j.micinf.2006.12.001
M3 - Article
C2 - 17314059
AN - SCOPUS:33847370391
SN - 1286-4579
VL - 9
SP - 282
EP - 290
JO - Microbes and Infection
JF - Microbes and Infection
IS - 3
ER -