Comparative genome analysis ofEnterococcus cecorumreveals intercontinental spread of a lineage of clinical poultry isolates

Abstract

Enterococcus cecorumis an emerging pathogen responsible for osteomyelitis, spondylitis, and femoral head necrosis causing animal suffering, mortality, and requiring antimicrobial use in poultry. Paradoxically,E. cecorumis a common inhabitant of the intestinal microbiota of adult chickens. Despite evidence suggesting the existence of clones with pathogenic potential, the genetic and phenotypic relatedness of disease-associated isolates remains little investigated. Here, we sequenced and analyzed the genomes and characterized the phenotypes of more than 100 isolates, the majority of which were collected over the last ten years in 16 French broiler farms. Comparative genomics, genome-wide association study, and measured susceptibility to serum, biofilm forming capacity, and adhesion to chicken type II collagen were used to identify features associated with clinical isolates. We found that none of the tested phenotypes could discriminate origin of the isolates or phylogenetic group. Instead, we found that most clinical isolates are grouped phylogenetically and our analyses selected six genes that discriminate 94% of isolates associated with disease from those that are not. Analysis of the resistome and the mobilome revealed that multidrug-resistant clones ofE. cecorumcluster in few clades and that integrative conjugative elements and genomic islands are the main carriers of antimicrobial resistance. This comprehensive genomic analysis shows that disease-associated clones ofE. cecorumbelong mainly to one phylogenetic clade.IMPORTANCEEnterococcus cecorumis an important pathogen in poultry worldwide. It causes a number of locomotor disorders and septicemia, particularly in fast-growing broilers. Animal suffering, antimicrobial use, and associated economic losses require a better understanding of disease-associatedE. cecorumisolates. To address this need, we performed whole genome sequencing and analysis of a large collection of isolates responsible for outbreaks in France. By providing the first dataset on the genetic diversity and resistome ofE. cecorumstrains circulating in France, we pinpoint an epidemic lineage probably also circulating elsewhere and which should be targeted preferentially by preventive strategies in order to reduce the burden ofE. cecorum-related diseases.