Genome Sequencing Reveals E. coli Diversity

Researchers at the Harvard School of Public Health and the Broad Institute of MIT and Harvard have completed a whole-genome sequencing of the E. coli bacterial strains responsible for the deadly 2011 outbreaks in Germany and France.

The outbreaks, which killed 50 people, were traced to two sources of sprouts in Germany contaminated with particularly virulent strains of E. coli.

The study, which will appear in the journal “Proceedings of the National Academy of Sciences,” found genetic variations between the German and French strains that had been previously undetectable using traditional sequencing tools. Whole genome sequencing allowed the researchers to precisely discriminate among strains at the nucleotide level.

“By applying this approach to this outbreak, and even more to outbreaks in the future as it becomes routine, we’re going to be able to pick [apart] the detailed patterns of transmission,” said senior author William P. Hanage, an epidemiology professor at HSPH. “And if we can figure out how things are transmitted around, then we’re going to be able to intervene to stop them.”

Harvard Medical School professor of pediatrics Clifford W. Lo, who was not affiliated with the study, added that “this was a new strain that was causing this disease, and it was tracked down in record time.”

Usually, more genetically diverse bacterial strains are correlated with a larger infected human population, but in this case, all the strains connected to the larger German outbreak were found to have nearly identical genomes while the genomes of E. coli strains in France showed greater diversity.

In this context, diversity refers to a high number of differences in the genetic coding between strains of one bacterial species.

“The surprising finding was that there is a difference in [genetic] diversity between the [French and German] outbreaks,” said Yonatan H. Grad, a researcher involved in the study. “In the German strain there was very little diversity, but in the much smaller French outbreak there was considerably more.”

Explanations proposed by the authors including the possibility that there was more original genetic diversity in the French E. coli strains, that there were differences in mutation rates between German and French strains, and that the German strain underwent a population bottleneck effect—a phenomenon in which an evolutionarily less fit portion of the E. coli population was killed or otherwise prevented from reproducing.

Biochemical bacterial typing—currently the standard procedure for bacterial identification—can take several days, but it is nevertheless faster than whole-genome sequencing. However, Lo predicts that with improvements in technology, the high-resolution methods used in this study will be used more extensively in the future.

“I don’t think that genomic sequencing will prevent death once an outbreak happens,” he said. “But it could be used ... to find out what the bug is doing and where it came from.”

—Staff writer Ola Topczewska can be reached at atopczewska@college.harvard.edu.