This research is published online first in the New England Journal of Medicine on July 27, 2011.
“This research gives us insights into the reasons why this particular strain of E. coli is so virulent, allows us to hypothesize about the evolution of this bacterium and provides clinically relevant information about the treatment of this infection,” said Waldor, a researcher in the Channing Lab at BWH and senior author of the paper. Waldor is also a Professor of Medicine at Harvard Medical School and an Investigator of the Howard Hughes Medical Institute.
Researchers sequenced the outbreak strain and 11 related strains and determined that the outbreak strain was a member of the enteroaggregative (EAEC) pathotype of E. coli with serotype O104:H4. The outbreak strain differs from other O104:H4 strains because it contains genes encoding Shiga toxin 2 (Stx2) and a distinct set of additional virulence and antibiotic resistance factors. Researchers also discovered that expression of the stx2 gene was increased by certain antibiotics including ciprofloxacin. Additionally, researchers report that horizontal genetic exchange with a Shiga toxin-producing enterohemorrhagic E. coli (EHEC) strain likely underlies the emergence of this highly virulent outbreak strain.
“Based on our understanding the genetic profile of this E. coli strain, we would suggest caution in the use of certain antibiotics to treat these infections,” Waldor said. “This analysis also emphasizes the importance of the exchange of DNA between bacteria in the emergence of new pathogens. There is evidence that the outbreak strain acquired many genes by horizontal genetic exchange, which means that bacteria gave DNA not only to the bacteria that they reproduce, but also to neighboring bacteria.”
Researchers employed single molecule, real-time (SMRTTM) DNA sequencing technology from Pacific Biosciences of California, Inc. The exceptionally long sequencing reads generated by the SMRT sequencing enabled the team to detect larger-scale deletions, insertions, inversions and other structural variation between the O104:H4 outbreak samples and the other O104:H4 EAEC samples that were sequenced.
The authors included scientists from BWH, Pacific Biosciences, the University Of Maryland School Of Medicine, the University Of Virginia School Of Medicine, the World Health Organization Collaborating Centre for Reference and Research on Escherichia coli and Klebsiella, the Statens Serum Institut, Hvidovre University Hospital, and Harvard Medical School.
“These important findings are truly the result of an international collaboration. This work, which is the most detailed genetic profile of this pathogen to date, couldn’t have happened without the combined efforts of this group, which yielded rapid but in depth analysis of the origins of this new and deadly pathogen” Waldor said.