Role of the sar locus of Staphylococcus aureus in induction of endocarditis in rabbits

Cheung, Ambrose L.; Yeaman, Michael R.; Sullam, Paul M.; Witt, Mallory D.; Bayer, Arnold S.

doi:10.1128/iai.62.5.1719-1725.1994

Cited by 65 publications

(41 citation statements)

References 33 publications

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“…The rabbit endocarditis model was used to examine the virulence of a SarA mutant strain due to the effect of SarA on the levels of fibrinogen-and fibronectin-binding proteins. In this assay, the SarA-mutant strain had a significantly lower infectivity rate than the parent organism [43].…”

Section: In Vivo Studies Of Virulence Factor Regulationmentioning

confidence: 92%

Virulence regulation inStaphylococcus aureus: the need for in vivo analysis of virulence factor regulation

Pragman

Schlievert

2004

FEMS Immunology &Amp; Medical Microbiology

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Staphylococcus aureus is a pathogenic microorganism that is responsible for a wide variety of clinical infections. These infections can be relatively mild, but serious, life-threatening infections may result from the expression of staphylococcal virulence factors that are coordinated by virulence regulators. Much work has been done to characterize the actions of staphylococcal virulence regulators in broth culture. Recently, several laboratories showed that transcriptional analyses of virulence regulators in in vivo animal models or in human infection did not correlate with transcriptional analyses accomplished in vitro. In describing the differences between in vitro and in vivo transcription of staphylococcal virulence regulators, we hope to encourage investigators to study virulence regulators using infection models whenever possible.

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Section: In Vivo Studies Of Virulence Factor Regulationmentioning

confidence: 92%

Virulence regulation inStaphylococcus aureus: the need for in vivo analysis of virulence factor regulation

Pragman

Schlievert

2004

FEMS Immunology &Amp; Medical Microbiology

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“…As many of the virulence factors (e.g. hemolysins and fibronectin binding proteins) are regulated by sarA and agr (97), the contributory roles of these two regulators to virulence have been evaluated in several animal model systems including the rabbit endocarditis model (97,98), the endophthalmitis model (99)(100)(101), the murine arthritis model (102,103), the rabbit osteomyelitis model (104), the murine subcutaneous infection model (42) and, more recently, the murine brain abscess model (105). The results of these published studies will not be described in full detail here.…”

Section: The Role Of Global Regulators In Virulencementioning

confidence: 99%

“…In this context, it is highly appropriate to envision bacterial response as a subset of genes activated by the host microenvironment. Clearly, SarA and agr are regulatory elements that control the expression of virulence determinants in vivo as demonstrated in several animal studies (42,(98)(99)(100)(101)(102)(103)(104)(105). The discovery of additional SarA homologs in S. aureus has significantly increased the complexity of the regulatory circuit.…”

Section: Perspectivesmentioning

confidence: 99%

Global regulation of virulence determinants in Staphylococcus Aureus by the SarA protein family

Ambrose¹

2002

Front Biosci

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In S. aureus, the production of virulence determinants such as cell wall adhesins and exotoxins during the growth cycle is controlled by global regulators such as SarA and agr. Genomic scan reveals 16 two-component regulatory systems (e.g. agr and sae) as well as a family of SarA homologs in S. aureus. We call the SarA homologs the SarA protein family. Many of the members in this protein family are either small basic proteins (<153 residues) or two-domain proteins in which a single domain shares sequence similarity to each of the small basic proteins. Recent crystal structures of SarR and SarA reveal dimeric structures for these proteins. Because of its structure and unique mode of DNA binding, SarR, and possibly other SarA family members, may belong to a new functional class of the winged-helix family, accommodating long stretch of DNA with bending points. Based on sequence homology, we hypothesize that the SarA protein family may entail homologous structures with similar DNA-binding motifs but divergent activation domains. An understanding of how these regulators interact with each other in vivo and how they sense environmental signals to control virulence gene expression (e.g. alpha-hemolysin) will be important to our eventual goal of disrupting the regulatory network.

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“…The regulation of virulence determinant production in S. aureus involves several global regulatory loci; of these, sar and agr are the best characterized (15,45,54,56), though other regulators have been described (27,30). Inactivation of the sar or agr locus results in a pleiotropic decrease in levels of exoproteins and an overproduction of surface proteins, while mutants are less virulent than the parental strain in several animal models (1,15,17,18,39,45,54,56).…”

mentioning

confidence: 99%

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

Chan¹,

Foster²

1998

J. Bacteriol.

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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 ␣-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.

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Role of the sar locus of Staphylococcus aureus in induction of endocarditis in rabbits

Cited by 65 publications

References 33 publications

Virulence regulation inStaphylococcus aureus: the need for in vivo analysis of virulence factor regulation

Virulence regulation inStaphylococcus aureus: the need for in vivo analysis of virulence factor regulation

Global regulation of virulence determinants in Staphylococcus Aureus by the SarA protein family

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

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