Disease relevance of pvdS

• Exotoxin A production in Pseudomonas aeruginosa requires the iron-regulated pvdS gene encoding an alternative sigma factor [1].
• The oxygen- and iron-dependent sigma factor pvdS of Pseudomonas aeruginosa is an important virulence factor in experimental infective endocarditis [2].
• The pvdS gene is required for expression from promoters of at least two pyoverdine synthesis genes and can cause expression from these promoters in Escherichia coli, where they are otherwise inactive [3].

High impact information on pvdS

• Neither toxA nor regAB mRNA was detectable in a delta pvdS mutant [1].
• Fur from the C6 mutant in DNase I footprint experiments failed to protect the promoter region of the pvdS gene, but it retained some weak binding activity in gel mobility shift assays [4].
• In a delta pvdS deletion mutant, ETA was produced at low levels of less than 5% compared to wild type, but still in response to iron starvation, and introduction of a functional pvdS gene on a plasmid fully restored wild-type levels and normal iron regulation of ETA synthesis [1].
• Quantitative real-time PCR revealed that stationary-phase cells of the rpoN mutant grown without an antimicrobial agent had approximately 4- to 140- and 2- to 14-fold-higher levels of transcripts of the pvdS and vqsR genes, respectively, than the wild-type strain [5].
• A pvdS mutant of P. aeruginosa, deficient in pyoverdine production, was shown to be susceptible to biapenem [5].

Biological context of pvdS

• Consistent with the presence of such a consensus sequence, addition of iron repressed transcription of the pvdS gene in P. aeruginosa [6].
• A genomic pvdS mutant of PAO, constructed by allelic exchange mutagenesis, produced no pyoverdin and did not allow transcription from the pvd promoters [6].
• The promoter region of pvdS has the sequence that matches well the consensus binding site for the E. coli Fur protein, a global negative regulatory protein that represses the transcription of the iron-repressible genes [6].

Associations of pvdS with chemical compounds

• Thus, pvdS (but not toxA) appears to be required for optimal virulence of P. aeruginosa, particularly in tissues preferentially exposed to high O2 tensions (e.g., aortic vegetations) [2].

Regulatory relationships of pvdS

• The iron-regulated expression of ptxR under microaerobic conditions from the P2 promoter of ptxR is mediated indirectly by Fur through the iron-regulated expression of pvdS [7].

Other interactions of pvdS

• In contrast, pvdS-mediated iron regulation of ptxR under aerobic conditions is Fur independent [7].
• Our results support the hypothesis that the P. aeruginosa Fur repressor indirectly controls pvdA transcription through the intermediary sigma factor PvdS; in the presence of sufficient iron, Fur blocks the pvdS promoter, thus preventing PvdS expression and consequently transcription of pvdA and other pyoverdin biosynthesis genes [8].

Analytical, diagnostic and therapeutic context of pvdS

• Interaction of the Fur repressor with a 150-bp fragment encompassing the pvdS promoter was demonstrated in vivo by the Fur titration assay and confirmed in vitro by gel retardation experiments with a partially purified Fur preparation [8].

References