The population-level impact of Enterococcus faecalis genetics on intestinal colonisation and extraintestinal infection

Abstract

Enterococcus faecalis is a commensal pathogenic bacterium commonly found in the human gastrointestinal tract and a cause of opportunistic infections typically associated with multidrug resistance. The E. faecalis genetic changes associated with pathogenicity and extraintestinal infection, particularly through gut-to-bloodstream translocation, are poorly understood. Here, we investigate the E. faecalis genetic signatures associated with intestinal colonisation and extraintestinal infection and infection of hospitalised and non-hospitalised individuals using heritability estimation and a genome-wide association study (GWAS). We analysed 750 whole-genome sequences of faecal and bloodstream E. faecalis isolates from hospitalised patients and non-hospitalised individuals, respectively, predominantly in Europe. We found that E. faecalis infection of individuals depending on their hospitalisation status and extraintestinal infection are heritable traits and that ~24% and ~34% of their variation is explained by the considered genetic effects, respectively. Further, a GWAS using linear mixed models did not pinpoint any clear enrichment of individual genetic changes in isolates from different isolation sites and individuals with varying hospitalisation statuses, suggesting that these traits are highly polygenic. Altogether, our findings indicate that E. faecalis infection and extraintestinal infection are influenced by variation in genetic, host, and environmental factors, and ultimately the opportunistic pathogenic lifestyle of this versatile host generalist bacterium.

The bacterial genetic determinants of Escherichia coli capacity to cause bloodstream infections in humans

“…coli whole genomes in colonization and in infection in a case-control study, as done before for Klebsellia pneumoniae [ 69 ], S . pneumoniae [ 70 ], Staphylococcus aureus [ 71 , 72 ], Enterococcus faecalis [ 73 ], Neisseria meningitidi s [ 74 ]. These previous GWAS studies presented a range of results, from low heritability (2.6% for S .…”

“…Bacterial genetics has a significant role in determining pathogenicity, even after basic host factors (age and sex) have been accounted for. The present study compares E. coli whole genomes in colonization and in infection in a case-control study, as done before for Klebsellia pneumoniae [69], S. pneumoniae [70], Staphylococcus aureus [71,72], Enterococcus faecalis [73], Neisseria meningitidis [74]. These previous GWAS studies presented a range of results, from low heritability (2.6% for S. aureus carriage vs. BSI [71]), to intermediate (34% for E. faecalis intestinal colonization vs. extraintestinal infection, 36.5% for N. meningitidis carriage vs. invasive meningococcal disease), and an analogously large heritability of 70% for S. pneumoniae invasive disease vs. carriage, along with a handful of significant SNPs [70].…”