Enterococcal Endocarditis: Hiding in Plain Sight.

Gary M. Dunny,Kristi L. Frank,Aaron M. T. Barnes

doi:10.3389/fcimb.2021.722482

Abstract

Enterococcus faecalis is a major opportunistic bacterial pathogen of increasing clinical relevance. A substantial body of experimental evidence suggests that early biofilm formation plays a critical role in these infections, as well as in colonization and persistence in the GI tract as a commensal member of the microbiome in most terrestrial animals. Animal models of experimental endocarditis generally involve inducing mechanical valve damage by cardiac catheterization prior to infection, and it has long been presumed that endocarditis vegetation formation resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage. Here we review both historical and contemporary animal model studies demonstrating the robust ability of E. faecalis to directly attach and form stable microcolony biofilms encased within a bacterially-derived extracellular matrix on the undamaged endovascular endothelial surface. We also discuss the morphological similarities when these biofilms form on other host tissues, including when E. faecalis colonizes the GI epithelium as a commensal member of the normal vertebrate microbiome - hiding in plain sight where it can serve as a source for systemic infection via translocation. We propose that these phenotypes may allow the organism to persist as an undetected infection in asymptomatic individuals and thus provide an infectious reservoir for later clinical endocarditis.

Highlights

Enterococci are a paradox among bacteria: adaptable to a wide range of environmental conditions, resistant to numerous antibiotic compounds, and flexible enough to thrive as both common commensals and opportunistic pathogens across a range of clinical situations (Lebreton et al, 2014; Goh et al, 2017; Gaca and Lemos, 2019)
Enterococcus faecalis – originally described in 1906 as Streptococcus faecalis before being transferred to the genus Enterococcus in 1984 – has been recognized as a causative agent in endocarditis since its original English publication (Andrewes and Horder, 1906). (For a thorough review of the original clinical identification and publication of the bacteria eventually labeled as the genus Enterococcus, see Lebreton et al, 2014)
Numerous papers in the older literature reported that enterococcal endocarditis appears to occur in a significant fraction of patients without obvious pre-existing gross endothelial damage or cardiac structural defects (Geraci and Martin, 1954; Toh and Ball, 1960). (As often occurs in older literature, the precise identification of specific bacterial species can be difficult to determine definitively.) These clinical findings have been reported in several animal model systems, including pigs (Jones, 1969) and rabbits (Durack et al, 1973)

Summary

INTRODUCTION

Enterococci are a paradox among bacteria: adaptable to a wide range of environmental conditions (pH, temperature, salinity, bile acids, etc.), resistant to numerous antibiotic compounds, and flexible enough to thrive as both common commensals and opportunistic pathogens across a range of clinical situations (Lebreton et al, 2014; Goh et al, 2017; Gaca and Lemos, 2019). Combined with the lack of gross systemic host responses to this colonization over several weeks, and the ability of E. faecalis to attach to undamaged endothelium, these findings support a hypothesis in which attachment of enterococci to the cardiac endothelium plays a similar role in the prelude to pathogenic endocarditis as it does in non-pathogenic gut epithelial colonization We review both the recent and historical evidence for this type of colonization, demonstrate the ways in which the canonical model does and does not align with the recent discoveries in the field, and discuss the potential paths forward to better understand the pathophysiology surrounding this increasingly important clinical infection

BACKGROUND

Findings

DISCUSSION