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Infect. Immun., 01 1998, 218-223, Vol 66, No. 1
PM Schlievert, PJ Gahr, AP Assimacopoulos, MM Dinges, JA Stoehr, JW Harmala, H Hirt and GM Dunny
We investigated the importance of enterococcal aggregation substance (AS)
and enterococcal binding substance (EBS) in rabbit models of Enterococcus
faecalis cardiac infections. First, American Dutch belted rabbits were
injected intraventricularly with 10(8) CFU and observed for 2 days. No
clinical signs of illness developed in animals given AS- EBS- organisms,
and all survived. All rabbits given AS- EBS+ organisms developed signs of
illness, including significant pericardial inflammation, but only one of
six died. All animals given AS+ EBS- organisms developed signs of illness,
including pericardial inflammation, and survived. All rabbits given AS+
EBS+ organisms developed signs of illness and died. None of the rabbits
receiving AS+ EBS+ organisms showed gross pericardial inflammation. The
lethality and lack of inflammation are consistent with the presence of a
superantigen. Rabbit and human lymphocytes were highly stimulated in vitro
by cell extracts, but not cell-free culture fluids, of AS+ EBS+ organisms.
In contrast, cell extracts from AS- EBS- organisms weakly stimulated
lymphocyte proliferation. Culture fluids from human lymphocytes stimulated
with AS+/EBS+ enterococci contained high levels of gamma interferon and
tumor necrosis factor alpha (TNF-alpha) and TNF- beta, which is consistent
with functional stimulation of T-lymphocyte proliferation and macrophage
activation. Subsequent experiments examined the abilities of the same
strains to cause endocarditis in a catheterization model. New Zealand White
rabbits underwent transaortic catheterization for 2 h, at which time
catheters were removed and animals were injected with 2 x 10(9) CFU of test
organisms. None of the animals given AS- EBS- organisms developed
vegetations or showed autopsy evidence of tissue damage. Rabbits given AS-
EBS+ or AS+ EBS- organisms developed small vegetations and had splenomegaly
at autopsy. All rabbits given AS+ EBS+ organisms developed large
vegetations and had splenomegaly and lung congestion at autopsy. Similar
experiments that left catheters in place for 3 days revealed that all
rabbits given AS- EBS- or AS+ EBS+ organisms developed vegetations, but
animals given AS+ EBS+ organisms had larger vegetations and autopsy
evidence of lung congestion. These experiments provide direct evidence that
these two cell wall components play an important role in the pathogenesis
of endocarditis as well as in conjugative plasmid transfer.
Copyright © 1998, American Society for Microbiology
Aggregation and binding substances enhance pathogenicity in rabbit models of Enterococcus faecalis endocarditis
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455-0312, USA. pats@lenti.med.umn.edu
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