Disease relevance of atxA

• This CO2 effect is observed only in the presence of another pXO1 gene, atxA, which encodes a transactivator of anthrax toxin synthesis [1].
• Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis [2].
• Using a pag-lacZ transcriptional construct to measure pag promoter activity, we cloned in Bacillus subtilis a gene (atxA) whose product acts in trans to stimulate anthrax toxin expression [3].
• Preliminary work relied on plasmid vectors in both E. coli and B. thuringiensis expressing the atxA gene [4].

High impact information on atxA

• We identified a cluster of germination genes extending for 3608 nucleotides between the pag and atxA genes on the B. anthracis virulence plasmid pXO1 [5].
• The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence [1].
• These data suggest that the atxA gene product also regulates toxin gene expression during infection [1].
• Moreover, the antibody response to all three toxin proteins is decreased significantly in atxA-null mutant-infected mice [1].
• We determined that in addition to the toxin and capsule genes, atxA controls expression of numerous other genes on both plasmids and the chromosome [6].

Biological context of atxA

• A derivative strain cured of pXO1 produced less capsular substance than the parent strain harbouring both pXO1 and pXO2, and electroporation of the strain cured of pXO1 with a plasmid containing the cloned atxA gene resulted in an increased level of capsule production [2].
• Two regulatory genes, acpA and atxA, have been reported to control expression of the Bacillus anthracis capsule biosynthesis operon capBCAD [7].
• Here we report that an atxA-null mutant exhibits phenotypes unrelated to toxin and capsule synthesis [8].

Associations of atxA with chemical compounds

• Surprisingly, mRNA levels of atxA, a regulator of exotoxin gene expression, rose in the presence of GML [9].
• Numerous transposon-generated promoter-lacZ fusions at distinct loci on pXO1 exhibit CO2-enhanced atxA-dependent expression similar to that observed for the toxin genes [8].

Regulatory relationships of atxA

• One atxA-independent and two atxA-regulated start sites map upstream of capB [10].

Other interactions of atxA

• In B. subtilis cells, the B. anthracis promoters from the atxA and abrB genes were regulated by AbrB(BS), and the B. subtilis promoter from the yxbB operon was regulated by AbrB(BA) [11].
• Transcriptional analyses of a genetically complete strain indicate that capB expression is several hundred-fold higher during growth in 5% CO2 compared to growth in air. atxA was expressed appreciably during growth in air and induced only 2.5-fold by CO2 [10].
• Autogenous control of the operon may involve atxA, a trans-acting positive regulator of pagA [12].
• A 182-kb plasmid, pXO1, carries the anthrax toxin genes and the genes responsible for their regulation of transcription, namely atxA and, pagR, the second gene of the pag operon [13].
• Whereas pXO2 harbours the cap operon coding for the capsule, pXO1 contains the pag, lef, and cya genes coding for protective antigen, lethal, and oedema factors, respectively, as well as the atxA regulatory gene [14].

Analytical, diagnostic and therapeutic context of atxA

• Previously, the anthrax toxins activator ( atxA) mRNA had been used in our laboratory for the development of a biosensor for the detection of a single B. anthracis spore within 12 h [15].

References