The researchers, led by Grad and senior authors Hung and William Hanage, associate professor of epidemiology at HSPH, analyzed isolates of E. coli bacteria from both the German and French outbreaks. Based on conventional molecular epidemiological analysis, the E. coli strains from the outbreaks in Germany and France appear identical.

However, by harnessing the Broad’s expertise in whole-genome sequencing and analysis, the researchers were able to determine that there were small, but measurable, differences among the isolates. They made two surprising findings: All the strains connected to the larger German outbreak were found to be nearly identical, while the strains in France showed greater diversity; and the German isolates appeared to be a subset of the diversity seen in the French isolates.

“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 Hanage.

Another hypothesis offered by the researchers is that there was uneven distribution of diversity in the original shipment of contaminated seeds.

As costs for genomic sequencing decline, these tools, combined with traditional epidemiological techniques, can provide greater insight into the emergence and spread of infectious diseases and will help guide preventive public health measures in the future.

Support for this study was provided by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH); Infectious Disease Program of the Broad Institute; NIH’s National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) Award; Danish Council for Strategic Research; Institut de Veille Sanitaire.