Control of virulence gene expression in Bacillus anthracis.

The atxA gene is an important regulator of virulence gene expression in Bacillus anthracis. atxA positively regulates expression of the three genes encoding the anthrax toxin proteins and at least one gene is required for capsule production. Here we report that an atxA-null mutant exhibits phenotypes unrelated to toxin and capsule synthesis. An atxA-null mutant grows poorly on minimal media and sporulates more efficiently than the parent strain. 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. We also report that the atxA-activated pagA gene (encoding the protective antigen toxin protein) is co-transcribed with a 300-bp gene, pagR, located downstream of pagA. The predicted protein product of pagR has some amino acid sequence similarity to transcriptional regulators in other organisms. Our data indicate that pagR represses expression of pagA and atxA. pagR also controls expression of some CO2/atxA-activated transcriptional fusions on pXO1 that do not correspond to the toxin genes. Regulation of these fusions and pagA and pagR may be due to changes in AtxA levels, or may be independent of atxA expression.