Zoonotic infections with enterohemorrhagic Escherchia coli O157 have emerged as a serious threat to human health. Conventional sequence-based analyses indicate that most human infections originate from particular pathogenic lineages. In this study, we apply a machine-learning approach to complex pangenome information and predict the human infection potential of cattle E. coli O157 isolates. We demonstrate that only a small subset of bovine strains is likely to cause human disease, even within previously defined pathogenic lineages. The approach was tested across isolates from the United Kingdom and United States and verified with food and cattle isolates from outbreak investigations. This finding has important implications for targeting of control strategies in herds.

Abstract

Sequence analyses of pathogen genomes facilitate the tracking of disease outbreaks and allow relationships between strains to be reconstructed and virulence factors to be identified. However, these methods are generally used after an outbreak has happened. Here, we show that support vector machine analysis of bovine E. coli O157 isolate sequences can be applied to predict their zoonotic potential, identifying cattle strains more likely to be a serious threat to human health. Notably, only a minor subset (less than 10%) of bovine E. coli O157 isolates analyzed in our datasets were predicted to have the potential to cause human disease; this is despite the fact that the majority are within previously defined pathogenic lineages I or I/II and encode key virulence factors. The predictive capacity was retained when tested across datasets. The major differences between human and bovine E. coli O157 isolates were due to the relative abundances of hundreds of predicted prophage proteins. This finding has profound implications for public health management of disease because interventions in cattle, such a vaccination, can be targeted at herds carrying strains of high zoonotic potential. Machine-learning approaches should be applied broadly to further our understanding of pathogen biology.