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Scientists Shed Light on Germany’s Deadly Pathogen

As the devastating outbreak of E. coli began unfolding in Germany, there was an urgent need to learn more about the unusual pathogen that was making hundreds of people sick.

So data from the genome sequencing of the rare E. coli serotype O104 were instantly released via the Internet to researchers around the world, and a flurry of information-swapping followed. 

Discussions about this strange bacterium went viral, “rapidly communicated via blogs, Twitter and private web pages,” according to an editorial published Tuesday in Eurosurveillance.

This combination of advanced molecular typing technology and electronic communication has led to what the authors describe as intriguing, preliminary analyses “outside the standard peer-reviewed scientific publication route.”

The accompanying report in Eurosurveillance, written by an international team of investigators, emphasizes the importance of working collaboratively to quickly unlock the secrets of an infectious organism.

“The rapid exchange of information, strains and DNA fingerprints within national and international public health and food safety networks has been vital in the quick and alternative assessment of the public health significance causing the outbreak of HUS in Germany in May and June 2011,” the authors state.

The contributions have resulted not only in “important new findings on the nature and possible origin of the epidemic strain,” but the microbiology has helped to devise new lab screening tools for hospitals diagnosing patients and for public health authorities investigating the outbreak.

Among the findings:

The outbreak strain is not a typical virulent Shiga toxin-producing  (STEC) strain, the authors write, but a much rarer and “hypervirulent” hybrid — an enteroaggregative E. coli (EAggEC) now armed with the ability to produce Shiga toxin.

Adding to its virulence is a receptor for iron-chelating aerobactin, which is associated with extraintestinal E. coli strains, like those that cause diseases such as meningitis, sepsis and urinary tract infections outside the intestinal tract.

The genome of the outbreak strain “clustered closest” to an EAggEC strain isolated in 2002, with the addition of the Shiga toxin factor and antibiotic resistance genes.

EAggEC causes diarrhea in travelers and persistent diarrhea in infants and young children in countries with poor sanitation, but is common in all parts of the world, industrialized and developing nations alike, the report explains. Unlike STEC, which have an animal reservoir (primarily ruminants), EAggEC have a human reservoir, so E. coli O104 likely does too.

“This observation suggests the startling possibility,” the authors note, “that this new O104 strain may have the capacity to persist among human populations, perhaps indefinitely.”

EAggEC is capable of causing diarrhea in adults and children, even in the absence of Shiga toxin, notes the report, which cites a 1993 outbreak of the bacteria among Japanese children that sickened 2,700.

The authors also state that “the role of EAggEC as an important pathogen in AIDS patients continues to develop, and EAggEC now ranks among the most important enteric pathogens in this population group.”

While most STEC are eae positive, the outbreak O104 strain in Germany is eae negative — eae being genetic coding for the protein intimin, which the bacteria use to attach to the intestinal wall. The Eurosurveillance report says, ” … it is indeed conceivable that the enteroaggregative adherence phenotype could have allowed these E. coli O104 strains to colonise the intestinal mucosa of the affected patients as efficiently as typical eae-positive STEC/VTEC strains.

“The different mechanism of adhesion might also explain why this strain is more likely to cause severe disease in adults rather than children …”  But the authors say this factor needs more study, and that the different rates of hemolytic uremic syndrome (HUS) between adults and children in Germany might just reflect a difference in exposures to the outbreak source.

Hybrid strains of E. coli such as O104 aren’t new, the researchers suggest. For example, one HUS outbreak caused by a “mixed pathotype,” but a different serotype, was reported from France in 1998.  But the authors found five previously reported cases of diarrhea or HUS caused by O104:H4: Germany in 2001, France in 2004, South Korea in 2005, Georgia in 2009 and Finland in 2010.

The 2011 German outbreak strain most closely resembles the Georgian strain genetically, they said, but there is no known epidemiological link between the two so “the meaning of this finding remains elusive.” 

The Eurosurveillance editorial says that since June 10, the number of newly reported cases of infection and HUS in Germany has been gradually decreasing, “which suggests we may finally be reaching the end of the outbreak.”

The search for the source and vehicle of the outbreak has been “long and arduous,” the editorial went on, adding that it was “extensive investigations” that finally implicated the organic sprout farm in Lower Saxony near Hamburg.

“Sprouts produced at this farm had been distributed to many of the incriminated restaurants and catering facilities, and thus identified as the likely vehicle of infection,” the authors wrote.

As of Tuesday, the outbreak toll was 3,335 ill, 817 with HUS and 37 dead, including a 2-year-old boy, the first child to die.

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