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1 November 2006

Volume 43, Number 9
Clinical Infectious Diseases 2006;43:1160–1167
© 2006 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2006/4309-0006$15.00
DOI: 10.1086/508195
MAJOR ARTICLE

Shiga Toxin Activatable by Intestinal Mucus in Escherichia coli Isolated from Humans: Predictor for a Severe Clinical Outcome

Martina Bielaszewska,1,2

Alexander W. Friedrich,1,2

Thomas Aldick,1

Robin Schürk‐Bulgrin,1 and

Helge Karch1,2

1National Consulting Laboratory on Hemolytic Uremic Syndrome, Institute for Hygiene, University of Münster, and 2Interdisciplinary Center for Clinical Research (IZKF) Münster, Münster, Germany

Background.Some Escherichia coli produce Shiga toxin (Stx) in which cytotoxicity is increased (activated) by intestinal mucus and elastase (Stx2dactivatable). These strains are highly virulent in mice, but their association with human disease is poorly understood. We investigated the prevalence of Stx2dactivatable among Stx‐producing E. coli (STEC) isolated from humans and the association between production of this Stx and the clinical outcome of infection.

Methods.A total of 922 STEC isolates obtained from patients with hemolytic uremic syndrome or bloody or nonbloody diarrhea or from asymptomatic carriers were tested for the gene encoding Stx2dactivatable by PCR and PstI restriction analysis. The toxin activatibility by human and mouse intestinal mucus and by an elastase was determined by quantifying the cytotoxicity using the Vero cell assay.

Results.The stx2d‐activatable gene was identified in 60 (6.5%) of 922 STEC strains; in 31 of these strains, it was the sole stx gene. Thirty of these 31 strains produced Stx2dactivatable. All of them lacked the intimin‐encoding eae gene. Among eae‐negative STEC, which typically cause mild diarrhea or asymptomatic infection, production of Stx2dactivatable was significantly associated with the ability to cause severe disease, including bloody diarrhea ( ), and with systemic complications, such as hemolytic uremic syndrome ( ).

Conclusions.Production of Stx2dactivatable by the infecting STEC may predict a severe clinical outcome of the infection, with progression to hemolytic uremic syndrome. A prompt and comprehensive subtyping of stx genes in STEC isolates is necessary to alert the treating physician that a patient is at risk of developing hemolytic uremic syndrome, even though the infecting STEC lacks eae.

Received 18 May 2006; accepted 5 July 2006; electronically published 2 October 2006.

Reprints or correspondence: Dr. Martina Bielaszewska, Institut für Hygiene, Universität Münster, Robert Koch Str. 41, 48149 Münster, Germany ().

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