Glucose-Dependent Activation ofBacillus anthracisToxin Gene Expression and Virulence Requires the Carbon Catabolite Protein CcpA

Sensing environmental conditions is an essential aspect of bacterial physiology and virulence. InBacillus anthracis , the causative agent of anthrax, transcription of the two major virulence factors, toxin and capsule, is triggered by bicarbonate, a major compound in the mammalian body. Here it is shown that glucose is an additional signaling molecule recognized byB. anthracis for toxin synthesis. The presence of glucose increased the expression of the protective antigen toxin component-encoding gene (pagA ) by stimulating induction of transcription of the AtxA virulence transcription factor. Induction ofatxA transcription by glucose required the carbon catabolite protein CcpA via an indirect mechanism. CcpA did not bind specifically to any region of the extendedatxA promoter. The virulence of aB. anthracis strain from which theccpA gene was deleted was significantly attenuated in a mouse model of infection. The data demonstrated that glucose is an important host environment-derived signaling molecule and that CcpA is a molecular link between environmental sensing andB. anthracis pathogenesis.