Prospective genomics in epidemics – lessons from the German E. coli outbreak

By Jennifer Laloup (EveryONE)

Today we published an article by Mellmann et al. entitled, Prospective Genomic Characterization of the German Enterohemorrhagic Escherichia coli O104:H4 Outbreak by Rapid Next Generation Sequencing Technology. The following is an opinion piece by Dr. Niyaz Ahmed, a section editor for PLoS ONE and the academic editor of this paper.  He is an expert in the area of molecular epidemiology and genomics of bacterial pathogens at the University of Hyderabad, India.


When a monstrously virulent strain of never-before-seen E. coli suddenly appeared in Germany last month, the rush to decode became an immediate focus. Several groups became engaged simultaneously to crack the genome of the underlying bug and then followed a huge crowd-sourcing effort on the internet as soon as the genome sequences were made available. Given that reasonable data were made available by these authors within 60 hours of the outbreak, not much of the evolutionary history of the organism had been dissected and a great deal of the interpretation remained vague.

An informed, scientific treatise was needed to help health control authorities and policy makers launch a serious mitigation campaign; this work, in that sense, constitutes the first official report on the genomic footprint of the underlying E. coli strain. The authors report chronological (step-wise) recombination of the genome in the outbreak strains over a period of ten years. This reveals the extraordinary capability of certain pathogens to recombine so that a devastating phenotype finally emerges with a multi-dimensional fitness advantage. Further, the study of Mellmann et al. demonstrates the might of present-day sequencing technologies such as Ion Torrent in enabling genome-guided epidemiology, diagnostics, and interventions.

I have no hesitation to say that the study carried out by Mellmann et al. is truly a technical masterpiece, a first time proof-of-principle whereby next generation sequencing could be harnessed in real-time when certain 'gold standards' such as serotyping failed miserably. This report has an important bearing on the new proposed field of 'epidemic forecasting' in which the spread potentials of a pathogen could be predicted based on genomic fingerprints – in other words, predicting if the infection will assume pandemic proportions.  The finding that the E. coli strains analyzed were enteroaggregative (EAEC) could explain this. EAECs could persist in recovered or subclinical cases and that they could be carried by the latter on travel routes worldwide.

One of the possible shortcomings of the study could be that it is silent on the mechanistic details of 'adornment' of these bacteria with several layers of fitness – multiple antibiotic resistance, acid tolerance, enteroaggregative capacity and shigatoxin production all bundled up in one 'naturally' chimeric strain in just 10 years is extremely dramatic!  The pace of evolution of the German outbreak strains has surpassed even Helicobacter pylori, an organism notorious for its speed of recombination, recasting its entire genome every forty years. We recently had an opportunity to sequence and look at H. pylori genomes hierarchically obtained across ten years. We did not find major insertion, deletion and substitution events.

Technology helped with the dissection of the E. coli epidemic in hours and days, but the editorial process also was seamless and prompt enough to enable rapid dissemination of results. Open and early access is very important for the dissemination of findings during epidemic times because much of the control and mitigation measures need planning in the light of latest research findings.