Virulence of Bacillus Anthracis Depends on Blood Bicarbonate

Scientists have identified bicarbonate as the human blood component that causes the Gram-positive bacteria, Bacillus anthracis, to become virulent.

Bicarbonate is a chemical found in all body fluids and organs that play a major role in maintaining the pH balance in cells, and it provides the signal for B. anthracis to unleash its virulence factors. Without the presence of the bicarbonate transporter in the bloodstream, the bacteria do not become virulent. This finding opens up new avenues of exploration for the development of treatments for other bacterial infections.

The major cause in the increase of community and hospital- acquired bacterial infections are Gram-positive bacteria. The U.S. Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA estimates that as many as 10 % of all patients, or about 2 million people, contract nosocomial infections each year. These bacteria are often resistant to multiple antibiotics, making the problem a growing public health concern and the need for new antibacterial treatment more urgent.

Scripps Research Institute (La Jolla CA, USA) associate professor Marta Perego, Ph.D. and colleagues identified a previously unknown adenosine triphosphate (ATP)-binding cassette transporter (ABC-transporter)--which is identified by the gene number BAS2714-12--that was essential to transporting bicarbonate. ABC-transporters use the energy of ATP hydrolysis to transport various substrates across cellular membranes. When the genes that code for the BAS2714-12 ABC transporter were deleted, the rate of bicarbonate uptake inside the cell greatly decreased, induction of toxin gene expression did not occur, and virulence in an animal model of infection was abolished.

Elimination of carbon dioxide production within the bacterial cell had no effect on toxin production, suggesting that CO2 activity is not essential to virulence factor induction and that bicarbonate, not CO2, was the signal essential for virulence induction.

This finding is significant because other pathogenic bacteria such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholerae have bicarbonate transport pathways similar to B. anthracis and possibly have similar virulence triggering mechanisms.

The study was published in the November 21, 2008 edition of the journal PLoS Pathogens.

Related Links:
U.S. Centers for Disease Control and Prevention
Scripps Research Institute