Genome evolution and the emergence of pathogenicity in avian Escherichia coli

Leonardos Mageiros,Evangelos Mourkas,Ben Pascoe,Keith A Jolley,Johan Pensar,Koji Yahara,Nicola J Williams,Kirsty Kemmett,Jessica K Calland,Lisa K Williams,Jonathan Porter,Samuel K Sheppard,Matthew D Hitchings,Edward J Feil,Jukka Corander,Susan Murray,Guillaume Méric,Thomas S Wilkinson,Sion C Bayliss

doi:10.1038/s41467-021-20988-w

Abstract

Chickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them. This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic Escherichia coli (APEC), emerges from ubiquitous commensal gut bacteria, with no single virulence gene present in all disease-causing isolates. Here, we address the underlying evolutionary mechanisms of extraintestinal spread and systemic infection in poultry. Combining population scale comparative genomics and pangenome-wide association studies, we compare E. coli from commensal carriage and systemic infections. We identify phylogroup-specific and species-wide genetic elements that are enriched in APEC, including pathogenicity-associated variation in 143 genes that have diverse functions, including genes involved in metabolism, lipopolysaccharide synthesis, heat shock response, antimicrobial resistance and toxicity. We find that horizontal gene transfer spreads pathogenicity elements, allowing divergent clones to cause infection. Finally, a Random Forest model prediction of disease status (carriage vs. disease) identifies pathogenic strains in the emergent ST-117 poultry-associated lineage with 73% accuracy, demonstrating the potential for early identification of emergent APEC in healthy flocks.

Highlights

Chickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them
The rate of accessory gene discovery did not plateau as the sampling increased (Supplementary Fig. 1), consistent with widespread acquisition of genes through horizontal gene transfer (HGT)
While only 15.5% of all annotated genes from the reference avian E. coli strain APEC_O1 were of unknown function, this number increased to 65.8% for the whole pangenome

Summary

Introduction

Chickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic Escherichia coli (APEC), emerges from ubiquitous commensal gut bacteria, with no single virulence gene present in all disease-causing isolates. Using a genome-wide association study (GWAS) approach[34,35], we analyse 568 E. coli genomes from commercial poultry farms, including isolates from healthy chickens and those from various systemic infection body sites, and identify genes and genetic elements associated with avian pathogenicity (Fig. 1). Having described an evolutionary context for understanding pathogen emergence, we use a machine learning approach to identify risk genotypes, that with further validation, could form a basis of diagnostics and interventions to improve animal health

Methods

Results

Conclusion