Affiliation:
1. Division of Infectious Diseases, Department of Medicine,1
2. Department of Microbiology and Molecular Genetics,2 and
3. Center for the Study of Emerging and Re-emerging Pathogens,3 University of Texas Medical School, Houston, Texas 77030
Abstract
ABSTRACT
Three
agr
-like genes (
fsrA
,
fsrB
, and
fsrC
, for
Enterococcus faecalis
regulator) were found upstream of the previously reported gelatinase gene (
gelE
) and a downstream putative serine protease gene (
sprE
; accession number
Z12296
) of
Enterococcus faecalis
OG1RF. The deduced amino acid sequence of
fsrA
shows 26% identity and 38% similarity to
Staphylococcus aureus
AgrA (the response regulator of the accessory gene regulator system in the
agr
locus), FsrB shows 23% identity and 41% similarity to
S. aureus
AgrB, and FsrC shows 23% identity and 36% similarity to
S. aureus
AgrC (the sensor transducer of Agr system). Northern blot analysis suggested that
gelE
and
sprE
are cotranscribed and that
fsrB
and
fsrC
are also cotranscribed in OG1RF. Northern blot analysis of
fsrA
,
fsrB
,
fsrC
,
gelE
, and
sprE
insertion mutants showed that
fsrB
,
fsrC
,
gelE
, and
sprE
are not expressed in
fsrA
,
fsrB
, and
fsrC
mutants, while insertion in an open reading frame further upstream of
fsrA
did not effect the expression of these genes, suggesting that
agr
-like genes may be autoregulated and that they regulate
gelE
and
sprE
expression, as further confirmed by complementation of
fsr
gene mutations with a 6-kb fragment which contains all three
fsr
genes in the shuttle vector, pAT18. Testing of 95 other isolates of
E. faecalis
showed that 62% produced gelatinase (Gel
+
), while 91% (including all Gel
+
strains) hybridized to a
gelE
probe; 71% (including all Gel
+
strains) hybridized to an
fsr
probe, corroborating the conclusion that both
gelE
and
fsr
are necessary for gelatinase production. Testing of
fsrA
,
fsrB
, and
sprE
mutants in a mouse peritonitis model showed that
sprE
and
agr
-like gene mutants resulted in highly significantly prolonged survival compared to the parent strain OG1RF, a finding similar to what we had previously shown for a
gelE
mutant. These results suggest that
sprE
and
agr
-like genes contribute to the virulence of
E. faecalis
OG1RF in this model.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
312 articles.
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