Watching the detectives: tracking the source of Europe’s latest E coli outbreakBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d3884 (Published 22 June 2011) Cite this as: BMJ 2011;342:d3884
All rapid responses
Jojanneke Heidema, Sabine CA Meijvis, Ger T Rijkers
The recent outbreak of Shiga toxin-producing Escherichia coli 0104:H4
in Germany is associated with a high incidence of hemolytic-uremic
syndrome (HUS) and death. While previous outbreaks of Escherichia coli
0157 reported HUS incidence of 6%, predominantly in children, the German
strain causes HUS in 20-25% of cases, 89% being adults.1 This increased
virulence of this strain might be caused by an activation of the innate
immune system of the host, triggered by the lectin pathway of complement
activation. Complement activation has been previously described in causing
the development of HUS associated with the Escherichia coli 0157 strain,
which was ascribed to the properties of the Shiga toxin.2,3
We compared two Escherichia coli 0104:H4 isolates from patients involved
in the current outbreak with two different Escherichia coli 0157 isolates
and two Escherichia coli strains that caused uncomplicated urinary tract
infections. We compared these strains for their ability to bind complement
components from serum of healthy donors. The bacteria were grown in
nutritional broth before they were heat inactivated (10 minutes at 70?C).
Subsequently either freshly thawed serum or buffered saline (control) was
added and bacteria were incubated for 30 min on ice. After washing, either
human mannose-binding lectin (MBL) or Ficolin-2 specific antibodies were
added, and fluorescence intensity was measured using flowcytometry. Both
of the Escherichia coli 0104:H4 strains, but none of the other
Escherichia coli strains, were able to bind large quantities of MBL and
Ficolin-2 when incubated with human serum (Figure 1). This finding was
reproduced in three consecutive experiments.
We therefore postulate that the increased virulence seen in the current
outbreak in Germany might be due to direct properties of the bacterium to
initiate the lectin pathway of complement activation in the host. As heat
inactivation probably denatures Shiga toxin, and because all heat
inactivated Escherichia coli 0157 strains were not able to bind complement
despite their ability to produce Shiga toxin, the Escherichia coli 0104:H4
strain might use different mechanisms to induce this response. It now
would be interesting to know whether MBL polymorphisms that cause MBL
deficiency are associated with a favorable outcome in patients infected
with Escherichia coli 0104:H4. We hope that our findings trigger
additional research into the underlying mechanisms of the virulence of
this German strain.
Figure 1) MBL (A) and Ficolin-2 (B) bind to Escherichia coli 0104:H4
when incubated with serum, but not to Escherichia coli 0157 (C and D).
1 Frank C, Werber D, Cramer JP, et al. Epidemic Profile of Shiga-
Toxin-Producing Escherichia coli O104:H4 Outbreak in Germany - Preliminary
Report. N Engl J Med 2011.
2 Orth D, Khan AB, Naim A, et al. Shiga toxin activates complement
and binds factor H: evidence for an active role of complement in hemolytic
uremic syndrome. J Immunol 2009; 182: 6394-400.
3 Stahl AL, Sartz L, Karpman D. Complement activation on platelet-
leukocyte complexes and microparticles in enterohemorrhagic Escherichia
coli-induced hemolytic uremic syndrome. Blood 2011; 117: 5503-13.
Competing interests: No competing interests