Opposing Roles of the
            <i>Staphylococcus aureus</i>
            Virulence Regulators, Agr and Sar, in Triton X-100- and Penicillin-Induced Autolysis

Fujimoto, David F.; Bayles, Kenneth W.

doi:10.1128/jb.180.14.3724-3726.1998

Cited by 74 publications

(29 citation statements)

References 17 publications

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“…In many cases, they are regulated at the post-translational level by substrate modification, selective transport, interaction with lipoteichoic acids and cationic peptides, proteolysis or environmental signals such as Na + ions (Cleveland et al ., 1975;Wecke et al ., 1986;Bierbaum and Sahl, 1987;Madiraju et al ., 1987;Holtje and Tuomanen, 1991;Tobin et al , 1994). Some of the murein hydrolases have been shown to be regulated at the transcriptional level by arlRS , lytRS and lrgAB ; however, the precise mode of regulation remains largely undefined (Brunskill and Bayles, 1996;Fujimoto and Bayles, 1998;.…”

Section: Introductionsupporting

confidence: 80%

Characterization of RAT, an autolysis regulator in Staphylococcus aureus

Ingavale

Wamel

Cheung

2003

Molecular Microbiology

126

161

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SummaryIn trying to identify genetic loci involved in the regulation of cap5 genes in Staphylococcus aureus , we isolated a transposon mutant that exhibited a growth defect, enhanced autolysis and increased sensitivity to Triton X-100 and penicillin, attributable in part to increased murein hydrolase activity. Analysis of the chromosomal sequence flanking the transposon insertion site revealed that the gene disrupted in the mutant encodes an open reading frame of 147 amino acids. We named this gene rat , which stands for regulator of autolytic activity. Sequence analysis indicated that Rat is homologous to the MarR and, to a lesser extent, the SarA protein families. Mutations in rat resulted in decreased expression of known autolytic regulators lytSR , lrgAB and arlRS . Gel shift studies indicated that Rat binds to the lytRS and arlRS promoters, thus confirming Rat as a DNA-binding protein to these known repressors of autolytic activity. As anticipated, rat appears to be a negative regulator of autolysin genes including lytM and lytN . These data suggest that the rat gene product is an important regulator of autolytic activity in S. aureus .

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Section: Introductionsupporting

confidence: 80%

Characterization of RAT, an autolysis regulator in Staphylococcus aureus

Ingavale

Wamel

Cheung

2003

Molecular Microbiology

126

161

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“…2B). Thus, the reduction of cell-bound FnBP found in the sar mutant is probably not due to an increased release of the protein into the culture medium, for example by increased expression of a murein hydrolase in the sar mutant (Fujimoto and Bayles, 1998).…”

Section: Resultsmentioning

confidence: 92%

Agr‐independent regulation of fibronectin‐binding protein(s) by the regulatory locus sar in Staphylococcus aureus

Wolz

Pöhlmann-Dietze

Steinhuber

et al. 2000

Molecular Microbiology

117

115

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Fibronectin‐binding proteins (FnBPs) are thought to be important for the attachment of Staphylococcus aureus during infection. The regulation of the genes fnbA and fnbB by the global regulatory loci sar and agr was examined using site‐specific regulatory mutants of S. aureus strain Newman. The results from binding assays using both aqueous and solid‐phase fibronectin as well as ligand blotting with biotinylated fibronectin showed that the expression of FnBPA is enhanced in the agr mutant but inhibited in the sar mutant and the sar–agr double mutant. The same regulatory pattern was observed in Northern blot analysis using fnbA‐specific probes. The introduction of sar on a multicopy plasmid increased the already enhanced fnbA transcription of the agr mutant. FnBPB was not detectable by ligand blotting and the fnbB promoter activity in promoter fusion assays was not affected by either sar or agr. The sequence encompassing ORF3 located upstream of sarA was found to be essential for the activation of fnbA transcription. We hypothesize that this sequence may modulate SarA expression and/or activity on the post‐transcriptional level. Gel shift assays demonstrated that SarA binds to the fnbA promoter fragments, probably as a dimer. DNase I footprinting assays with SarA revealed a protected area of 102 bp upstream of fnbA.

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“…coagulase) (2) and fibronectin binding proteins (22), and down-regulation in the synthesis of protein A (76), collagen binding protein (77), lipase (2) and proteases such as V8 protease (75), cysteine protease, aureolysin and staphopain (12) ( Table 2). More recently, the sarA locus has been shown to repress autolytic activity (78). Because of the suppressive effect of sarA on V8 protease and aureolysin, recent data from Karlsson and colleagues disclosed that the decrease in fibronectin binding protein expression in a sarA mutant may be attributable to surface protein modification by these two proteases (79).…”

Section: The Sara Locusmentioning

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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Opposing Roles of the Staphylococcus aureus Virulence Regulators, Agr and Sar, in Triton X-100- and Penicillin-Induced Autolysis

Cited by 74 publications

References 17 publications

Characterization of RAT, an autolysis regulator in Staphylococcus aureus

Characterization of RAT, an autolysis regulator in Staphylococcus aureus

Agr‐independent regulation of fibronectin‐binding protein(s) by the regulatory locus sar in Staphylococcus aureus

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

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