The enemy within us: lessons from the 2011 European Escherichia coli O104:H4 outbreak

Abstract

In response to the 2011 European health alert caused by a pathogenic Escherichia coli O104:H4 outbreak, the European Academy of Microbiology (EAM), established by the Federation of European Microbiological Societies (FEMS), convened a meeting in Paris on November 30th, 2011 on 'EHEC infection and control' attended by world renowned experts in pathogenic E. coli. The major aims of this group were to review the scientific issues raised by the outbreak, to assess the handling of the crisis at the scientific and political levels, and to propose future actions. Several conclusions, which will have impact on future potential E. coli outbreaks, are outlined here.

Figure 1. Timecourse of the outbreak

The top line shows the retrospective tracing of the fenugreek seed stocks that were linked by association to the German and French outbreak cases. The bottom line (note different scale) indicates significant events occurring at the clinical and diagnostic scenery during the outbreak. No direct connection between the two lines has been firmly established and the circumstances under which the E. coli O104:H4 strain came into contact with sprouts have not been documented. (1) Sample received at German National Consulting Laboratory for Hemolytic Uremic Syndrome; (2) Molecular subtyping data available based on partial gnd-sequencing (O104), fliC-RFLP-typing (H4), MLST (ST678); (3) Stx2 subtype confirmed by PCR and sequencing. ESBL phenotype confirmed; (4) Shotgun genome sequencing on Ion Torrent platform started at German National Consulting Laboratory for HUS. Publication in the Internet of a specific PCR for the differentiation of the outbreak clone from other EHEC; (5) Shotgun genome sequence available.

Figure 2. Minimum spanning tree of hemolytic uremic syndrome-associated enterohemorrhagic E. coli (HUSEC) strains based on multi-locus sequence typing

The red arrow points at the O104:H4 lineage.

Figure 3

Summary of virulence-associated genes in the genome of the O104:H4 outbreak strain.

Figure 4. Adherence of the E. coli outbreak strain

Aggregative ‘stacked-brick’ adherence pattern of the E. coli O104:H4 outbreak strain to cultured HCT-8 intestinal epithelial cells.

Figure 5. Mode of Shiga toxin action

The two component (AB) Shiga Toxin enters the mammalian cell through endocytosis, either mediated or not by clathrin, and is then transported from the endosome to the Golgi network using a section of the secretory pathway. This section, in which a multi-protein retromer complex is needed, is called the retrograde pathway (purple arrows). The toxin then reaches the endoplasmic reticulum (ER) where it is cleaved. The subunit A enters the cytoplasm and blocks protein synthesis at the ribosome, what is the ultimate reason for the toxicity. Small molecule drugs able to selectively block the passage of the toxin through the retrograde pathway to the Golgi network have been found. The toxin is then retained at the endosome where it does not exert virulent effects. Modified from Seaman & Peden (2010).