Role of SarA in Virulence Determinant Production and Environmental Signal Transduction in Staphylococcus aureus

Role of SarA in Virulence Determinant Production and Environmental Signal Transduction in Staphylococcus aureus
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DOI:
10.1128/jb.180.23.6232-6241.1998
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发表时间:
1998-12
影响因子:
3.2
通讯作者:
P. Chan;S. Foster
P. Chan;S. Foster
中科院分区:
生物学3区
文献类型:
--
作者:
P. Chan;S. Foster

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ABSTRACT The staphylococcal accessory regulator (encoded bysarA) is an important global regulator of virulence factor biosynthesis in Staphylococcus aureus. To further characterize its role in virulence determinant production, ansarA knockout mutant was created by insertion of a kanamycin antibiotic resistance cassette into the sarAgene. N-terminal sequencing of exoproteins down-regulated bysarA identified several putative proteases, including a V8 serine protease and a novel metalloprotease, as the major extracellular proteins repressed by sarA. In kinetic studies, thesarA mutation delays the onset of α-hemolysin (encoded byhla) 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 bysarA independently of the accessory gene regulator (encoded by agr), was specifically induced microaerobically. Transcriptional gene fusion and Western analysis revealed thatsarA up-regulates both toxic shock syndrome toxin 1 gene (tst) expression and staphylococcal enterotoxin B production, respectively. This study demonstrates the role ofsarA as a signal transduction regulatory component in response to aeration stimuli and suggests that sarAfunctions as a major repressor of protease activity. The possible role of proteases as regulators of virulence determinant stability is discussed.