Abstract
Bacillus anthracis overcome host immune response by producing capsule and secreting toxins. Production of these virulence factors in response to host environment was shown to be regulated by atxA, the major virulence regulator, that was shown to be activated by HCO3− and CO2. While toxin production is regulated directly by atxA, capsule production is mediated by either one of two regulators; acpA and acpB. In addition, it was demonstrated that acpA gene have at least two promotors were one of them was linked to atxA. We used a genetic approach to study capsule and toxin production under different conditions. Unlike previous works that used NBY-HCO3− medium in a CO2 enriched atmosphere, we used a sDMEM based medium in which toxins and capsule production can be induced in B. anthracis in ambient or CO2 enriched atmosphere. Using this system, we could differentiate between induction by 10% NRS, 10% CO2 or 0.75% HCO3−. In response to high CO2, capsule production is induced by acpA in an atxA independent manner, while little or no toxins (protective antigen PA) is produced. atxA is activated in response to serum in CO2 independent manner and induce toxins production and capsule production in an acpA or acpB dependent manner. HCO3− activates atxA as well, however in non-physiological concentrations. Our findings might be relevant to the first stages of inhalational infection were in the dendritic cell the germinating spore must be protected by the capsule without effecting cell migration to the draining lymph-node by toxin secretion.
Competing Interest Statement
The authors have declared no competing interest.