Genetic research on European E. coli outbreak provides unique insight

Escherichia coli

A study of the outbreak of E. coli that killed 50 people in Germany last summer and sickened thousands has yielded some clues about the emergence and spread of infectious diseases.

A team of researchers, led by Harvard University’s School of Public Health (HSPH) and the Broad Institute, traced the path of the E. coli outbreak in Germany and France during the summer of 2011. The study sought to determine the genetic make-up of the bacteria in one of the first uses of genome sequencing to study the dynamics of a food-borne outbreak. The study, said HSPH, provides further evidence that genomic tools can be used to investigate future outbreaks and provide greater insight into the emergence and spread of infectious diseases.

The study, conducted in collaboration with groups at the Pasteur Institute in France, Assistance Publique-Hôpitaux de Paris, and Statens Serum Institut in Denmark, was published on Feb. 6, in the online edition of Proceedings of the National Academy of Sciences.

In one of the study’s most surprising findings, researchers determined there were small, but measurable, differences among the isolates from Germany and France. All of the strains connected to the larger German outbreak were found to be nearly identical, while the strains in France showed greater diversity, said the researchers. The German isolates also appeared to be a subset of the diversity seen in the French isolates, they said.

"If genomes have fewer differences than we expect, like the German outbreak, it suggests that the outbreak might have passed through a bottleneck. A bottleneck might be something like disinfection procedures that killed most but not all of the bugs, or maybe passage through a single infected individual," said William Hanage, associate professor of epidemiology at HSPH.

The outbreak in Germany, caused by the strain E. coli O104:H4, led to around 4,000 cases of bloody diarrhea, 850 cases of hemolytic uremic syndrome (HUS), which can lead to kidney failure, and over 50 deaths. The source of the outbreak was traced to sprouts from an organic farm in Germany. In France, where 15 people were sickened with bloody diarrhea that progressed to HUS in nine people, the source of the outbreak was sprouts, germinated from seeds purchased at a garden retailer, that were served at a children's community center buffet. European investigators, using traditional epidemiological methods, traced the outbreaks to a shipment of seeds from Egypt that arrived in Germany in December 2009.

The intricacies that genetic sequencing provides can give scientists a leg-up in knowing how to handle future outbreaks. "A genome contains the record of a strain's evolutionary history, so by looking at the differences between the genomes of multiple bacteria from an outbreak we can get really useful clues about what happened in the outbreak,” said lead author Yonatan Grad, a research fellow in the Center for Communicable Disease Dynamics, Department of Epidemiology at HSPH and infectious disease physician at Brigham and Women's Hospital in Boston.