Dataset Information

Enterococcus faecalis colonizes and forms persistent biofilm microcolonies on undamaged endothelial surfaces in a rabbit endovascular infection model.

ABSTRACT: Infectious endocarditis (IE) is an uncommon disease with significant morbidity and mortality. The pathogenesis of IE has historically been described as a cascade of host-specific events beginning with endothelial damage and thrombus formation and followed by bacterial colonization of the nascent thrombus. Enterococcus faecalis is a Gram-positive commensal bacterial member of the gastrointestinal tract microbiota in most terrestrial animals and a leading cause of opportunistic biofilm-associated infections, including endocarditis. Here, we provide evidence that E. faecalis can colonize the endocardial surface without pre-existing damage and in the absence of thrombus formation in a rabbit endovascular infection model. Using previously described light and scanning electron microscopy techniques, we show that inoculation of a well-characterized E. faecalis lab strain in the marginal ear vein of New Zealand White rabbits resulted in rapid colonization of the endocardium throughout the heart within 4 days of administration. Unexpectedly, ultrastructural imaging revealed that the microcolonies were firmly attached directly to the endocardium in areas without morphological evidence of gross tissue damage. Further, the attached bacterial aggregates were not associated with significant cellular components of coagulation or host extracellular matrix damage repair (i.e. platelets). These results suggest that the canonical model of mechanical surface damage as a prerequisite for bacterial attachment to host sub-endothelial components is not required. Furthermore, these findings are consistent with a model of initial establishment of stable, endocarditis-associated E. faecalis biofilm microcolonies that may provide a reservoir for the eventual valvular infection characteristic of clinical endocarditis. The similarities between the E. faecalis colonization and biofilm morphologies seen in this rabbit endovascular infection model and our previously published murine gastrointestinal colonization model indicate that biofilm production and common host cell attachment factors are conserved in disparate mammalian hosts under both commensal and pathogenic contexts.

SUBMITTER: Barnes AMT

PROVIDER: S-EPMC8557322 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 microg/ml) and susceptible to teicoplanin (0.25 microg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d-alanyl-d-lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX(D) activity, which is not required in the absence of d-Ala-d-Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY(D) activity in the membrane fractions was inhibited by penicillin G. The mutations E(13)G in the region of d-alanine:d-alanine ligase (which is implicated in d-Ala1 binding in A902) and S(319)N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d-Ala-d-Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS(D) of BM4539 and BM4540 and a 1-bp deletion in vanS(D) of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS(D), had a G(140)E mutation in VanR(D) that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS(D) or vanR(D) gene that lead to constitutive resistance to vancomycin.

Dataset Information

Enterococcus faecalis colonizes and forms persistent biofilm microcolonies on undamaged endothelial surfaces in a rabbit endovascular infection model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets