The population-level impact of
Enterococcus faecalis
genetics on intestinal colonization and extraintestinal infection
Authors: Chaguza Chrispin , Pöntinen Anna K. , Top Janetta , Arredondo-Alonso Sergio , Freitas Ana R. , Novais Carla , Torres Carmen , Bentley Stephen D. , Peixe Luisa , Coque Teresa M. , Willems Rob J. L. , Corander Jukka 
Published: October 2023

Enterococcus faecalis
is a commensal bacterium of the human gastrointestinal tract that causes opportunistic infections. The
E. faecalis
genetic changes associated with pathogenicity, particularly gut-to-bloodstream translocation, remain poorly understood. Here, we performed a genome-wide association study (GWAS) of 736 whole-genome sequences of fecal and bloodstream
E. faecalis
isolates from hospitalized and nonhospitalized individuals, respectively, to identify
E. faecalis
genetic signatures associated with the patient’s hospitalization status and body isolation source. We found that infection by hospitalization status and extraintestinal infection are heritable traits, with ~40% and ~30% of their variation explained by
E. faecalis
genetics, respectively. Furthermore, a GWAS using linear mixed models did not pinpoint any clear overrepresentation of individual genetic changes by hospitalization status or body isolation source after controlling for the population structure. However, we observed elevated signals in a genomic region containing a prophage element. However, the lineages themselves and their associated virulence factors and antibiotic resistance genes showed variable frequency among blood and fecal isolates and in hospitalized and nonhospitalized individuals. Altogether, our findings indicate that
E. faecalis
infection by hospitalization status and body sites is partially influenced by the overall genetic background of the isolates and antibiotic resistance patterns rather than genetic variation at individual loci, which suggests a greater role of other host and environmental factors and ultimately the opportunistic pathogenic lifestyle of this versatile host generalist bacterium.

IMPORTANCE

Enterococcus faecalis
causes life-threatening invasive hospital- and community-associated infections that are usually associated with multidrug resistance globally. Although
E. faecalis
infections cause opportunistic infections typically associated with antibiotic use, immunocompromised immune status, and other factors, they also possess an arsenal of virulence factors crucial for their pathogenicity. Despite this, the relative contribution of these virulence factors and other genetic changes to the pathogenicity of
E. faecalis
strains remain poorly understood. Here, we investigated whether specific genomic changes in the genome of
E. faecalis
isolates influence its pathogenicity—infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection and intestinal colonization. Our findings indicate that
E. faecalis
genetics partially influence the infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection, possibly due to gut-to-bloodstream translocation, highlighting the potential substantial role of host and environmental factors, including gut microbiota, on the opportunistic pathogenic lifestyle of this bacterium.