LIKE PEELING AN ONION – SECOND LINE VIRULENCE IN BACILLUS ANTHRACIS

Bacillus anthracis is a spore forming gram positive bacteria that causes Anthrax. Anthrax is a fatal zoonotic disease that infects mainly herbivores but can also infect carnivores, like canines and large cats. The infection of humans usually involves contact with infected animals or animal products carrying spores, the infective form of the bacteria. There are four types of Anthrax defined by the route of infection, cutaneous, gastrointestinal, inhalational and intravenous and most of them result in 100% mortality in the absence of effective and timely antibiotic treatment. Pathogenicity of B. anthracis is correlated with two sets of virulence factors, the tripartite toxins and the poly-D-glutamic acid capsule. While the capsule protects the bacteria from lysis within the phagocytic immune cells, the secreted toxins interfere with the host immune response, resulting in systemic immunosuppression. We took a genetic approach and deleted the three toxin genes in the fully virulent Vollum strain and tested the effect of the mutation in the rabbit animal model. As expected, the toxins` deletions resulted in full attenuation of the strain in rabbits. As we have previously demonstrated the critical role of the toxins in interfering with the immune response on the first steps of host-pathogen interactions, we tested the effect of the toxins` deletion on the systemic phase of the disease. We created an artificial systemic infection by intravenous injection of the capsular toxin-deficient mutant, which resulted in the death of the host. This finding indicates that B. anthracis possess an additional, toxin-independent, virulence mechanism. In this presentation I will describe the genetic characterization of this toxin independent virulence.