Anthrax is caused by the Gram-positive bacterium, Bacillus anthracis. The disease mainly affects herbivorous mammals which ingest or inhale the spores while grazing, but can also be passed to humans by contact with infected animal products. Once within the host, the bacteria begin to multiply and infection typically proves lethal within a few days or weeks. Virulence requires expression of both the anthrax toxin and capsule genes, and one of the first factors found to be important in controlling virulence was elevated levels of CO2/bicarbonate which are thought to signal the presence of a mammalian host environment. It has been difficult to unravel the precise mechanism of virulence control because of the equilibrium between CO2, H2CO3, HCO3–, and CO32-, but a study by scientists at the Scripps Research Institute published in the journal PLos Pathogens has demonstrated that expression of a specific bicarbonate transporter is critical for virulence. Deletion of the genes for the transporter strongly decreased the rate of bicarbonate uptake ex vivo and abolished induction of toxin gene expression. Importantly, the strain lacking the transporter was avirulent in a mouse model of anthrax infection, demonstrating the importance of this pathway for recognition of the host environment and pathogenesis.
The identification of an essential bicarbonate transporter may be of relevance to other pathogens, such as Staphylococcus aureus, that also regulate expression of virulence factors in response to CO2/bicarbonate levels, and suggests a novel target for antibacterial intervention. Similar transporters have been identified and characterized in photosynthetic bacteria, and the availability of 3-dimensional structures of the bicarbonate binding domain of the Synechococcus transporter may help with the design of new inhibitors.