Abstract
Bacillus anthracis is an endemic soil bacterium that exhibits two different lifestyles. In the soil environment, B. anthracis undergoes a cycle of saprophytic growth, sporulation, and germination. In mammalian hosts, the pathogenic lifestyle of B. anthracis is spore germination followed by vegetative cell replication, but cells do not sporulate. During infection, and in specific culture conditions, transcription of the structural genes for the anthrax toxin proteins and the biosynthetic operon for capsule synthesis is positively controlled by the regulatory protein AtxA. A critical role for the atxA gene in B. anthracis virulence has been established. Here we report an inverse relationship between toxin production and sporulation that is linked to AtxA levels. During culture in conditions favoring sporulation, B. anthracis produces little to no AtxA. When B. anthracis is cultured in conditions favoring toxin gene expression, AtxA is expressed at relatively high levels and sporulation rate and efficiency are reduced. We found that a mutation within the atxA promoter region resulting in AtxA over-expression leads to a marked sporulation defect. The sporulation phenotype of the mutant is dependent upon pXO2-0075, an atxA-regulated open reading frame located on virulence plasmid pXO2. The predicted amino acid sequence of the pXO2-0075 protein has similarity to the sensor domain of sporulation sensor histidine kinases. It was shown previously that pXO2-0075 overexpression suppresses sporulation. We have designated pXO2-0075 “skiA” for “sporulation kinase inhibitor.” Our results indicate that in addition to serving as a positive regulator of virulence gene expression, AtxA modulates B. anthracis development.
Highlights
Sporulation is a developmental process undertaken by members of the Bacillus genus in response to unfavorable or nutrient-deplete growth conditions
Orthologs of the signal transduction phosphorelay are found in members of the Bacillus cereus group, including the anthrax-causing bacterium Bacillus anthracis, enabling these species to sporulate in a manner similar to that of B. subtilis (Stephenson and Hoch, 2002; Brunsing et al, 2005; Bongiorni et al, 2006, 2007)
We sought to examine sporulation of B. anthracis using different culture conditions: a rich medium incubated in air (PA-air), or a semi-defined minimal medium containing dissolved bicarbonate and incubated in 5% CO2 (CACO3)
Summary
In specific culture conditions, transcription of the structural genes for the anthrax toxin proteins and the biosynthetic operon for capsule synthesis is positively controlled by the regulatory protein AtxA. A critical role for the atxA gene in B. anthracis virulence has been established. During culture in conditions favoring sporulation, B. anthracis produces little to no AtxA. When B. anthracis is cultured in conditions favoring toxin gene expression, AtxA is expressed at relatively high levels and sporulation rate and efficiency are reduced. The predicted amino acid sequence of the pXO2-0075 protein has similarity to the sensor domain of sporulation sensor histidine kinases. We have designated pXO2-0075 “skiA” for “sporulation kinase inhibitor.”. Our results indicate that in addition to serving as a positive regulator of virulence gene expression, AtxA modulates B. anthracis development
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