Affiliation:
1. Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom
Abstract
ABSTRACT
The staphylococcal accessory regulator (encoded by
sarA
) is an important global regulator of virulence factor biosynthesis in
Staphylococcus aureus
. To further characterize its role in virulence determinant production, an
sarA
knockout mutant was created by insertion of a kanamycin antibiotic resistance cassette into the
sarA
gene. N-terminal sequencing of exoproteins down-regulated by
sarA
identified several putative proteases, including a V8 serine protease and a novel metalloprotease, as the major extracellular proteins repressed by
sarA
. In kinetic studies, the
sarA
mutation delays the onset of α-hemolysin (encoded by
hla
) expression and reduces levels of
hla
to approximately 40% of the parent strain level. Furthermore, SarA plays a role in signal transduction in response to microaerobic growth since levels of
hla
were much lower in a microaerobic environment than after aerobic growth in the
sarA
mutant. An exoprotein exhibiting hemolysin activity on sheep blood, and up-regulated by
sarA
independently of the accessory gene regulator (encoded by
agr
), was specifically induced microaerobically. Transcriptional gene fusion and Western analysis revealed that
sarA
up-regulates both toxic shock syndrome toxin 1 gene (
tst
) expression and staphylococcal enterotoxin B production, respectively. This study demonstrates the role of
sarA
as a signal transduction regulatory component in response to aeration stimuli and suggests that
sarA
functions as a major repressor of protease activity. The possible role of proteases as regulators of virulence determinant stability is discussed.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
191 articles.
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