Disease relevance of pagA

• We studied the effects on Bacillus anthracis growth and the virulence gene (pagA, lef, and cya) expression of the QS inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, which is naturally synthesized by the marine alga Delisea pulchra, as well as a related compound and synthetic derivatives [1].
• Through quantitative reverse transcription-PCR assays, this toxin-inhibitory effect was shown to occur at the transcriptional level, since amounts of mRNA for pagA (PA), lef (LF), and cya (edema factor) were reduced [2].
• Protective antigen (PA) is a central virulence factor of Bacillus anthracis and a key component in anthrax vaccines [3].

High impact information on pagA

• Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol [4].
• Protective antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthracis, the organism responsible for anthrax [5].
• Protective antigen (PA) is a component of the Bacillus anthracis lethal and edema toxins and the basis of the current anthrax vaccine [6].
• We sequenced the protective antigen gene (pagA) from 42 representative outbreak isolates and determined they all had a pagA sequence indistinguishable from the Ames strain (PA genotype I) [7].
• When furanones were added to midlog-phase cultures of B. anthracis strains with LacZ reporters in pagA, lef, or cya, growth was inhibited, and expression of these virulence genes was inhibited to a proportionately greater extent [1].

Chemical compound and disease context of pagA

• Selection of Anthrax Toxin Protective Antigen Variants That Discriminate between the Cellular Receptors TEM8 and CMG2 and Achieve Targeting of Tumor Cells [8].

Biological context of pagA

• This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs [9].
• In an effort to produce anthrax vaccine in large quantities and free of extraneous bacterial contaminants, PA was expressed in transgenic tobacco chloroplasts by inserting the pagA gene into the chloroplast genome [10].
• Here we show that a 300-bp gene located downstream of pagA is cotranscribed with pagA and represses expression of the operon [11].
• Eight tested isolates possessed the pagA and capB genes indicating the presence of both virulence plasmids, while two isolates revealed only pagA and lacked pXO2 [12].
• Protective antigen-mediated antibody response against a heterologous protein produced in vivo by Bacillus anthracis [13].

Anatomical context of pagA

• Antigen-Specific CD4+ T Cells Recognize Epitopes of Protective Antigen following Vaccination with an Anthrax Vaccine [14].
• Protective antigen (PA) binding to macrophage cell line RAW264.7 > HUVECs >> A549 cells [15].

Other interactions of pagA

• Autogenous control of the operon may involve atxA, a trans-acting positive regulator of pagA [11].
• The gene encoding the protective antigen (pagA) was detected in 29 of 29 virulent B. anthracis strains, and the gene encoding the capsular protein B (capB) was detected in 28 of 29 of the same strains [16].
• A pagR mutant exhibited increased steady-state levels of pagA mRNA, indicating that pagR negatively controls expression of the operon [11].

Analytical, diagnostic and therapeutic context of pagA

• Chloroplast integration of the pagA gene was confirmed by PCR and Southern analysis [10].
• Protective antigen (PA)-based vaccination is an effective countermeasure to anthrax infection [17].
• Protective antigen as a correlative marker for anthrax in animal models [18].
• Protective antigen and toxin neutralization antibody patterns in anthrax vaccinees undergoing serial plasmapheresis [19].

References