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The bicarbonate transporter is essential for Bacillus anthracis lethality
Adam C Wilson1, Magali Soyer, James A Hoch
1Department of Molecular and Experimental Medicine, Division of Cellular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Plos Pathogens
|November 22, 2008
Summary
Bacillus anthracis virulence relies on a novel bicarbonate transporter essential for toxin gene expression. This transporter
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Bacillus anthracis virulence gene expression is induced by elevated CO2/bicarbonate levels.
- The mechanism and in vivo relevance of this induction are not fully understood.
Purpose of the Study:
- To identify the mechanism responsible for bicarbonate-mediated induction of virulence factors in B. anthracis.
- To determine the role of this mechanism in vivo.
Main Methods:
- Genetic deletion of a candidate ABC transporter (BAS2714-12).
- Measurement of bicarbonate uptake ex vivo.
- Assessment of virulence gene expression.
- Evaluation of bacterial virulence in a mouse model.
- Inhibition of carbonic anhydrase activity.
Main Results:
- A novel ABC transporter (BAS2714-12) was identified as essential for bicarbonate induction of virulence genes.
- Deletion of the transporter abolished toxin gene induction and reduced bicarbonate uptake.
- The transporter deletion strain was avirulent in mice.
- Bicarbonate, not CO2, was identified as the essential signaling molecule for virulence induction.
Conclusions:
- A novel bicarbonate ABC transporter is critical for Bacillus anthracis virulence.
- This transporter mediates the induction of toxin and capsule gene expression in response to host bicarbonate levels.
- The transporter represents a potential target for novel antibacterial interventions against B. anthracis and potentially other pathogens.
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