Control of the
            <i>Staphylococcus aureus</i>
            Toxic Shock
            <i>tst</i>
            Promoter by the Global Regulator SarA

Andrey, Diego O.; Renzoni, Adriana; Monod, Antoinette; Lew, Daniel Pablo; Cheung, Ambrose L.; Kelley, William L.

doi:10.1128/jb.00146-10

Cited by 42 publications

(68 citation statements)

References 58 publications

(80 reference statements)

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“…This is also consistent with a study that could not correlate agr polymorphisms, including agrC-inactivating mutations, with varied production of TSST-1 (12). Also, the staphylococcal accessory regulator (SarA) has previously been demonstrated to bind directly to the tst promoter region (13), and depending upon the genetic background, has been reported to function as either a positive or negative regulator of TSST-1 expression (13)(14)(15). Furthermore, carbon catabolite protein A (CcpA) acts as a repressor of TSST-1 (16), which explains the initial observation that TSST-1 expression is repressed by glucose (17).…”

supporting

confidence: 76%

“…In that work, repression of TSST-1 was clearly correlated to repression of agr, a well-established positive regulator of TSST-1 expression (10), although the precise details as to how TSST-1 is regulated by agr are not known. Nevertheless, mutation of agr does not completely abolish TSST-1 expression (10,13,15,18), and quorum sensing inhibitors based on the agr autoinducing peptide structure also do not eliminate TSST-1 expression (30). Furthermore, in the agr mutant background, TSST-1 could be further repressed by the lactobacillus signals (18), indicating that repression of TSST-1 was not entirely dependent upon agr.…”

Section: Discussionmentioning

confidence: 86%

“…Although SarA is known to bind to P tst (13), given the complete repression of TSST-1 in the saeS deletion background, we hypothesized that SaeR, the response regulatory of the Sae system, would directly regulate TSST-1 transcription. We first assessed the P tst promoter for a potential SaeR binding motif (25,29).…”

Section: Resultsmentioning

confidence: 99%

“…4A). Since SarA binds directly to the tst promoter (13), this implies that in the context of TSST-1 regulation in S. aureus MN8, the role of SarA is to compete with SaeR-mediated activation of tst transcription. This is also consistent with the overlapping binding sites of SarA (13) and the SaeR binding motifs localized by the EMSAs (Fig.…”

Section: Discussionmentioning

confidence: 99%

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The SaeRS Two-Component System Is a Direct and Dominant Transcriptional Activator of Toxic Shock Syndrome Toxin 1 in Staphylococcus aureus

et al. 2016

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Toxic shock syndrome toxin 1 (TSST-1) is a Staphylococcus aureus superantigen that has been implicated in both menstrual and nonmenstrual toxic shock syndrome (TSS). Despite the important role of TSST-1 in severe human disease, a comprehensive understanding of staphylococcal regulatory factors that control TSST-1 expression remains incomplete. The S. aureus exotoxin expression (Sae) operon contains a well-characterized two-component system that regulates a number of important exotoxins in S. aureus, although regulation of TSST-1 by the Sae system has not been investigated. We generated a defined deletion mutant of the Sae histidine kinase sensor (saeS) in the prototypic menstrual TSS strain S. aureus MN8. Mutation of saeS resulted in a complete loss of TSST-1 expression. Using both luciferase reporter experiments and quantitative real-time PCR, we demonstrate that the Sae system is an important transcriptional activator of TSST-1 expression. Recombinant SaeR was able to bind directly to the tst promoter to a region containing two SaeR consensus binding sites. Although the stand-alone SarA transcriptional regulator has been shown to be both a positive and a negative regulator of TSST-1, deletion of sarA in S. aureus MN8 resulted in a dramatic overexpression of TSST-1. As expected, mutation of agr also reduced TSST-1 expression, but this phenotype appeared to be independent of Sae. A double mutation of saeS and sarA resulted in the loss of TSST-1 expression. This work indicates that the Sae system is a dominant and direct transcriptional activator that is required for expression of TSST-1. IMPORTANCEThe TSST-1 superantigen is an exotoxin, produced by some strains of S. aureus, that has a clear role in both menstrual and nonmenstrual TSS. Although the well-characterized agr quorum sensing system is a known positive regulator of TSST-1, the molecular mechanisms that directly control TSST-1 expression are only partially understood. Our studies demonstrate that the Sae two-component regulatory system is a positive transcriptional regulator that binds directly to the TSST-1 promoter, and furthermore, our data suggest that Sae is required for expression of TSST-1. This work highlights how major regulatory circuits can converge to fine-tune exotoxin expression and suggests that the Sae regulatory system may be an important target for antivirulence strategies. Staphylococcus aureus is both a common commensal of humans and a prominent bacterial pathogen that is responsible for an assortment of illnesses ranging from self-limiting superficial infections to life-threatening invasive diseases (1). While most infections caused by S. aureus involve the coordinated expression of numerous virulence factors, a few select diseases, including staphylococcal scalded skin syndrome, food poisoning, and toxic shock syndrome (TSS), require the expression of specific staphylococcal exotoxins (2).Staphylococcal TSS is a rare but devastating disease that is caused by S. aureus strains that secrete high levels of superantigens. Super...

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supporting

confidence: 76%

Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The SaeRS Two-Component System Is a Direct and Dominant Transcriptional Activator of Toxic Shock Syndrome Toxin 1 in Staphylococcus aureus

et al. 2016

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“…In addition, the S. aureus strains that harbor SAg genes 37 produce varying levels of the toxins. This can been attributed to the involvement of at 38 least four global regulators, agr, sarA, σ B and saeRS (Tseng, Zhang et al 2004;Andrey, bacteriophages, plasmids, SaPIs, and genomic islands (Johns and Khan 1988;Fitzgerald, 1 Monday et al 2001;Lindsay and Holden 2006;Ono, Omoe et al 2008), whereas the 2 recently described SElX is core genome-encoded (Wilson, Seo et al 2011) (Table 1).…”

mentioning

confidence: 99%