Control of virulence gene expression in Bacillus anthracis

Area of Science:

• Microbiology
• Bacterial Genetics
• Molecular Biology

Background:

• The atxA gene in Bacillus anthracis is a key regulator of virulence factors, including anthrax toxin and capsule production.
• Previous studies established atxA's role in positively regulating toxin gene expression.

Purpose of the Study:

• To investigate phenotypes of an atxA-null mutant beyond toxin and capsule synthesis.
• To identify novel genes and regulatory mechanisms controlled by atxA and CO2 levels.
• To characterize the function of the pagR gene in relation to atxA and virulence.

Main Methods:

• Construction and analysis of an atxA-null mutant in Bacillus anthracis.
• Generation of transposon-based promoter-lacZ fusions on the pXO1 plasmid.
• Analysis of gene co-transcription and protein sequence similarity.
• Assessment of gene expression under varying CO2 conditions.

Main Results:

• An atxA-null mutant displayed impaired growth on minimal media and enhanced sporulation.
• CO2-enhanced, atxA-dependent expression was observed for multiple loci on pXO1, similar to toxin genes.
• The pagA gene is co-transcribed with pagR, a novel gene that represses pagA and atxA expression.
• PagR also regulates other CO2/atxA-activated genes on pXO1, independent of atxA levels.

Conclusions:

• The atxA gene influences Bacillus anthracis growth and sporulation, in addition to virulence.
• The newly identified pagR gene acts as a repressor of atxA and toxin gene expression.
• PagR-mediated regulation may occur independently of atxA levels, suggesting complex regulatory networks.