The <i>srhSR</i> Gene Pair from <i>Staphylococcus aureus</i>:  Genomic and Proteomic Approaches to the Identification and Characterization of Gene Function

Throup, John; Zappacosta, Francesca; Lunsford, R. Dwayne; Annan, Roland S.; Carr, Steve; Lonsdale, John T.; Bryant, Alexander P.; McDevitt, Damien; Rosenberg, Martin; Burnham, Martin K. R.

doi:10.1021/bi0102959

Cited by 104 publications

(110 citation statements)

References 34 publications

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“…A fourth two-component system, SrrAB, recently identified by our group (18) and others (19), was found to inhibit RNAIII expression and may itself be repressed by agr. Mutants of srrAB are unable to grow normally under anaerobic conditions (18,19), and expression of srrAB was shown to regulate genes involved in energy metabolism (19).…”

Section: Figurementioning

confidence: 91%

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Quorum sensing in Staphylococcus infections

Yarwood¹,

Schlievert²

2003

J. Clin. Invest.

204

158

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Quorum sensing via the accessory gene regulator (agr) system has been assigned a central role in the pathogenesis of staphylococci, particularly Staphylococcus aureus. While the control of virulence gene expression in vitro by agr has been relatively straightforward to describe, regulation of both the quorum response itself and virulence genes in vivo is considerably more complex. The quorum response is highly dependent upon the environment in which the organism is grown and is strongly influenced by additional regulators that respond to signals other than cell density. There is increasing evidence that the agr phenotype may influence the behavior and pathogenesis of biofilm-associated S. aureus and S. epidermidis and may contribute to the chronic nature of some biofilm-associated infections.

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Section: Figurementioning

confidence: 91%

“…Mutants of srrAB are unable to grow normally under anaerobic conditions (18,19), and expression of srrAB was shown to regulate genes involved in energy metabolism (19). The signal for the system may be menaquinone, an intermediate in the oxidative respiratory pathway.…”

Section: Figurementioning

confidence: 99%

Quorum sensing in Staphylococcus infections

Yarwood¹,

Schlievert²

2003

J. Clin. Invest.

204

158

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“…A study by Vetter and Schleivert demonstrated that the inactivation of BrrA dramatically reduced the synthesis of lethal factor, edema factor, and protective antigen; however, the group led by Perego failed to observe a decrease in protective antigen synthesis (229,232). In staphylococci, the ResDE homolog is known as the staphylococcal respiratory response (SrrAB, also known as SrhSR) (221,238).…”

Section: Srrabmentioning

confidence: 99%

“…In addition, SrrA binds to the promoter region of icaADBC and activates transcription under anaerobic conditions; thus, the inactivation of srrAB decreases PIA biosynthesis (226). Concomitant with a decrease in PIA biosynthesis, srrAB inactivation increases the expression of the TCA cycle enzymes aconitase, succinate dehydrogenase, and fumarase and NADH dehydrogenase (221). Our laboratory recently demonstrated that PIA is synthesized when TCA cycle activity is repressed (190,230); thus, the effect of srrAB on PIA biosynthesis is twofold, with the direct regulation of icaADBC transcription and indirect regulation via the repression of TCA cycle activity.…”

Section: Srrabmentioning

confidence: 99%

At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci

Somerville

Proctor

2009

Microbiol Mol Biol Rev

329

348

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SUMMARY Bacteria live in environments that are subject to rapid changes in the availability of the nutrients that are necessary to provide energy and biosynthetic intermediates for the synthesis of macromolecules. Consequently, bacterial survival depends on the ability of bacteria to regulate the expression of genes coding for enzymes required for growth in the altered environment. In pathogenic bacteria, adaptation to an altered environment often includes activating the transcription of virulence genes; hence, many virulence genes are regulated by environmental and nutritional signals. Consistent with this observation, the regulation of most, if not all, virulence determinants in staphylococci is mediated by environmental and nutritional signals. Some of these external signals can be directly transduced into a regulatory response by two-component regulators such as SrrAB; however, other external signals require transduction into intracellular signals. Many of the external environmental and nutritional signals that regulate virulence determinant expression can also alter bacterial metabolic status (e.g., iron limitation). Altering the metabolic status results in the transduction of external signals into intracellular metabolic signals that can be “sensed” by regulatory proteins (e.g., CodY, Rex, and GlnR). This review uses information derived primarily using Bacillus subtilis and Escherichia coli to articulate how gram-positive pathogens, with emphasis on Staphylococcus aureus and Staphylococcus epidermidis, regulate virulence determinant expression in response to a changing environment.

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“…Although TRAP has its own promoter and termination site, the genes coding for two-component systems are usually located in the same operon. About 16 possible operons encoding two-component systems were identified in S. aureus (31,43,45), and many of these systems have not yet been fully characterized. It is possible that one of them might be involved in functional interactions with TRAP, using the latter as a putative phospho-relay.…”

Section: (Cat To Gct)mentioning

confidence: 99%

Quorum Sensing in Staphylococci Is Regulated via Phosphorylation of Three Conserved Histidine Residues

Gov

Borovok

Korem

et al. 2004

Journal of Biological Chemistry

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Staphylococcus aureus cause infections by producing toxins, a process regulated by cell-cell communication (quorum sensing) through the histidine-phosphorylation of the target of RNAIII-activating protein (TRAP). We show here that TRAP is highly conserved in staphylococci and contains three completely conserved histidine residues (His-66, His-79, His-154) that are phosphorylated and essential for its activity. This was tested by constructing a TRAP ؊ strain with each of the conserved histidine residues changed to alanine by site-directed mutagenesis. All mutants were tested for pathogenesis in vitro (expression of RNAIII and hemolytic activity) and in vivo (murine cellulitis model). Results show that RNAIII is not expressed in the TRAP ؊ strain, that it is non hemolytic, and that it does not cause disease in vivo. These pathogenic phenotypes could be rescued in the strain containing the recovered traP, confirming the importance of TRAP in S. aureus pathogenesis. The phosphorylation of TRAP mutated in any of the conserved histidine residues was significantly reduced, and mutants defective in any one of these residues were non-pathogenic in vitro or in vivo, whereas those mutated in a non-conserved histidine residue (His-124) were as pathogenic as the wild type. These results confirm the importance of the three conserved histidine residues in TRAP activity. The phosphorylation pattern, structure, and gene organization of TRAP deviates from signaling molecules known to date, suggesting that TRAP belongs to a novel class of signal transducers.

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The srhSR Gene Pair from Staphylococcus aureus: Genomic and Proteomic Approaches to the Identification and Characterization of Gene Function

Cited by 104 publications

References 34 publications

Quorum sensing in Staphylococcus infections

Quorum sensing in Staphylococcus infections

At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci

Quorum Sensing in Staphylococci Is Regulated via Phosphorylation of Three Conserved Histidine Residues

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