Enterococcal Endocarditis: Hiding in Plain Sight

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.

Keywords: biofilm; host colonization; immune evasion; infection source; microbial adherence.

Figure 1

Models of bacterial endovascular colonization. Canonical models of endovascular colonization typically involve an initial inflammatory event and/or cell surface damage, which leads to host factor recruitment, platelet aggregation, and finally bacterial colonization of the nascent thrombus. Recent research suggests that enterococci (among other bacterial species) can attach to the undamaged endothelial cells in some model systems without the involvement of significant host factors (adapted from Barnes et al., 2021).

Figure 2

E. faecalis attachment, microcolony formation, and biofilm development on a range of in vitro and in vivo substrates demonstrates morphological conservation. (A) OG1RF attachment and microcolony development in a leporine model of endovascular infection (96 hr) with pre-inoculation mechanical damage to the aortic valve via catheterization (bar = 50 μm); (B) OG1RF attachment and microcolony development in a leporine model of endovascular infection (96 hr) from an uncatheterized rabbit (bar = 50 μm); (C) E. faecalis OG1RF microcolony formation in vitro on an Aclar fluoropolymer membrane (8 hr; bar = 5 μm). (D) OG1RF colonization of the GI tract in a germ-free murine model (72 hr; bar = 5 μm).