title: The bicarbonate transporter is essential for Bacillus anthracis lethality.
abstract: In the pathogenic bacterium Bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. Elevated CO2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. We identified a previously uncharacterized ABC transporter (BAS2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essential to the bicarbonate induction of virulence gene expression. Deletion of the genes for the transporter abolished induction of toxin gene expression and strongly decreased the rate of bicarbonate uptake ex vivo, demonstrating that the BAS2714-12 locus encodes a bicarbonate ABC transporter. The bicarbonate transporter deletion strain was avirulent in the A/J mouse model of infection. Carbonic anhydrase inhibitors, which prevent the interconversion of CO2 and bicarbonate, significantly affected toxin expression only in the absence of bicarbonate or the bicarbonate transporter, suggesting that carbonic anhydrase activity is not essential to virulence factor induction and that bicarbonate, and not CO2, is the signal essential for virulence induction. The identification of this novel bicarbonate transporter essential to virulence of B. anthracis may be of relevance to other pathogens, such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera that regulate virulence factor expression in response to CO2/bicarbonate, and suggests it may be a target for antibacterial intervention.
authors.affiliation: Department of Molecular and Experimental Medicine, Division of Cellular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Wilson
authors.forename: Magali
authors.initials: M
authors.lastname: Soyer
authors.forename: James A
authors.initials: JA
authors.lastname: Hoch
authors.forename: Marta
authors.initials: M
authors.lastname: Perego
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D000881:Anthrax / Q000209:etiology; D001408:Bacillus anthracis / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*; D001426:Bacterial Proteins; D001639:Bicarbonates / Q000378:metabolism*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D037521:Virulence Factors / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; C534461:BAS2714 protein, Bacillus anthracis; D001426:Bacterial Proteins; D001639:Bicarbonates; D037521:Virulence Factors