Disease relevance of sigB

• Salicylic acid (SAL) may impact Staphylococcus aureus virulence by activating the sigB operon (rsbU-V-W-sigB), thus leading to reductions in alpha-toxin production and decreased fibronectin binding (L. I. Kupferwasser et al., J. Clin. Investig. 112:222-233, 2003) [1].
• Studies in experimental endocarditis confirmed the key roles of both sarA and sigB in mediating the antistaphylococcal effects of salicylic acid in vivo [2].
• The rsbU defect of strain 8325-4 has recently been repaired, and we used this strain (SH1000), along with its isogenic sigB-negative mutant, to investigate the contributions of RsbU and SigB in a murine model of septic arthritis [3].
• The gene cluster showed close similarities to the Bacillus subtilis sigB operon both in overall organization and in primary sequences of the gene products [4].
• A hybrid between the coding sequence of the first 11 amino acids of the gene 10 leader peptide of phage T7 (T7.Tag) and the putative sigB gene of S. aureus was constructed and cloned into Escherichia coli BL21(DE3)pLysS for overexpression from a T7 promoter [5].

High impact information on sigB

• Transcriptional analysis, fluorometry, and flow cytometry revealed evidence of salicylic acid-mediated activation of the stress-response gene sigB [2].
• Growth curve analyses revealed longer doubling times and lower final densities for SCVs than for normal strains. sigB activity was measured by transcription analysis of the sigB target gene asp23 [6].
• Our data further suggest that heparin stimulation of biofilm formation occurs neither through an increase in sigB activity nor through an increase in polysaccharide intracellular adhesin levels [7].
• Furthermore, infection of endothelial cells with isogenic mutants of various regulator genes revealed that apoptosis induction was dependent on the global regulator agr and the alternative sigma factor sigB, but not influenced by sarA [8].
• Two genes of the sigB operon, rsbU and rsbV, were deleted in an rsbU(+) strain (FDA486) to evaluate the contribution of these two genes to sigma(B) activity in Staphylococcus aureus [9].

Chemical compound and disease context of sigB

• Biofilm formation by Staphylococcus epidermidis depends on functional RsbU, an activator of the sigB operon: differential activation mechanisms due to ethanol and salt stress [10].
• Impact of sigB mutation on Staphylococcus aureus oxacillin and vancomycin resistance varies with parental background and method of assessment [11].
• In many gram positive bacteria, the mazEF-locus is located directly upstream of the sigB (stress sigma factor sigmaB) operon in a putative operon together with the upstream dal (aIr) gene (encoding D-alanine racemase) [12].

Biological context of sigB

• Furthermore, analyses determined that altered expression of sigB and sarA is not responsible for the salicylate-inducible mechanism, and sarA upregulation is associated with the PS(RS) phenotype [13].
• Both genes have similar effects on intrinsic vancomycin resistance, and the salicylate-inducible mechanism is not sigB- or sarA-dependent [13].
• Complementation experiments with sigB on a plasmid reduced expression of proteases and alpha-hemolysin dramatically, indicating that the high production of these exoproteins was associated with sigmaB deficiency [14].
• To evaluate the role of SigB in modulating the expression of virulence determinants in Staphylococcus aureus, we constructed a sigB mutant of RN6390, a prototypic S. aureus strain [15].
• The sigB gene of Staphylococcus aureus, coding for the alternate sigma factor B, has been deleted by allelic replacement mutagenesis [16].

Anatomical context of sigB

• The result suggests that sigB plays some important roles in cell wall synthesis and in resistance to antibiotics that perturb the cell wall synthesis [17].

Associations of sigB with chemical compounds

• The POC(r) phenotype is reliant on the S. aureus alternative transcription factor SigB, since inactivation of sigB abolished expression of elevated POC resistance and the reductions in vancomycin and oxacillin susceptibilities [18].
• Supplementation of Trypticase soy broth with NaCl (TSB(NaCl)) or ethanol (TSB(EtOH)), both of which are known activators of sigB, led to increased biofilm formation and PIA synthesis by S. epidermidis 1457 [10].
• Mutation of sigB caused a decrease in vancomycin resistance in two laboratory derived glycopeptide-intermediate S. aureus strains [11].
• Interestingly, we found 11 proteins at an enhanced level in a sigB mutant of S. aureus COL, among them enterotoxin B, alpha and beta hemolysin, serine proteases SplA and SplB, leukotoxin D, and staphopain homologues [19].

Regulatory relationships of sigB

• The effect of the sigB mutation on the enhanced expression of the alpha-hemolysin gene (hla) was primarily transcriptional [15].

Other interactions of sigB

• A plasmid-based hla-promoter:green fluorescent protein reporter system was constructed in 2 genetically related S. aureus strains: RN6390 (a natural sigma factor B [sigB]-deficient mutant), SH1000 (a sigB-repaired variant of RN6390 lineage), and their respective agr, sarA, agr/sarA, and sae mutants [20].
• In contrast, sigB activation by SAL was progressively more mitigated in the rsbU and rsbV mutants [1].
• However, RN6390 was recently shown to have a mutation in rsbU that results in a phenotype resembling that of a sigB mutant (I. Kullik et al., J. Bacteriol. 180:4814-4820, 1998) [21].
• Results showed that clinical SCVs persisted much more efficiently in cells than the hemB and prototype strains and that a sigB mutant was a poor persister [22].
• The rsbW (orf159) gene is immediately upstream of sigB [23].

Analytical, diagnostic and therapeutic context of sigB

• Detailed immunoblot analysis as well as a competitive enzyme-linked immunosorbent assay of the cell extract of the sigB mutant with anti-SarA monoclonal antibody 1D1 revealed that the expression of SarA was higher in the mutant than in the parental control [15].
• By using Western blotting and a sarA-lacZ reporter assay, the levels of SarA were found to be similar in strains 8325-4 and SH1000 (8325-4 rsbU(+)) and sigB mutant derivatives of these strains [24].
• Northern blots of strain COL, a sigB-positive strain, showed an inverse correlation between sigmaB expression and seb message. seb expression was also measured as a function of a seb promoter linked to green fluorescent protein (GFP) expression in RN6390, COL, and Newman [25].
• Typically, sigB mutants of methicillin-resistant strains had oxacillin minimum inhibitory concentrations (MICs) one-half of their parent strains [11].

References