Evidence for Neolithic acquisition of the high pathogenic island by Escherichia coli followed by recent selection

Abstract

Many genetic elements involved in virulence and pathogenicity have been identified in commensal bacteria that are also opportunistic pathogens, but how these elements evolve is less well known. Understanding the evolutionary history of virulence elements requires genomes sampled in commensalism in healthy hosts, as genomes from bacterial infections are biased towards higher pathogenicity. Here, using a rare collection of human commensal Escherichia coli sampled in France from 1980 to 2020, we inferred the evolutionary history of the High Pathogenicity Island (HPI), a key virulence factor of E. coli with an uncertain evolutionary origin. The most likely scenario implied a horizontal transfer of the HPI from Yersinia pestis/pseudotuberculosis to the Enterobacterales, including E. coli, [~]4,700 years ago, coinciding with a period of increased population densities and human-animal interactions. The element subsequently spread in E. coli, with signs of positive epistasis with phylogroups B2 and F, and was positively selected in the last 100 years. Our work sheds light on the history and mode of evolution of virulence in an important opportunistic pathogen. It suggests the Neolithic period may have favored not only the emergence of zoonotic pathogens but also gene transfer between bacterial species, enriching the gene repertoire of major pathogens with potentially important implications on public health nowadays. Significance statement"Pathogenicity islands" are groups of genes that can be gained and lost on the chromosome of bacterial species and make them more pathogenic and virulent, but their evolutionary origin is unknown. We studied the origin and evolution of the High Pathogenicity Island of the major opportunistic pathogen Escherichia coli using molecular dating and phylogenetic analyses on very large genomic databases. We found that this island likely transferred from Yersinia pestis/pseudotuberculosis to E. coli 4,000 years ago, a period of increased population densities and intensified human-animal interactions, and was positively selected in the last 100 years. Thus, the origin of virulence can trace back to exchanges of mobile genetic elements that may be favored by particular circumstances in human history and have important consequences on human health nowadays.