Abstract
Nonencapsulated (∆pXO2) Bacillus anthracis strains are commonly used as vaccines and for anthrax research, mainly in the mouse model. Previously, we demonstrated that the infection of rabbits, intranasally or subcutaneously, with the spores of a fully virulent strain results in the systemic dissemination of the bacteria, meningitis, and death, whereas ∆pXO2 strains are fully attenuated in this animal model. We used the intravenous inoculation of rabbits to study the pathogenicity of the ∆pXO2 strain infection. Bacteremia, brain bacterial burden, and pathology were used as criteria to compare the Vollum∆pXO2 disease to the wild type Vollum infection. To test the role of adhesion in the virulence of Vollum∆pXO2, we deleted the major adhesion protein BslA and tested the virulence and immunogenicity of this mutant. We found that 50% of the rabbits succumb to Vollum∆pXO2 strain following i.v. infection, a death that was accompanied with significant neurological symptoms. Pathology revealed severe brain infection coupled with an atypical massive bacterial growth into the parenchyma. Contrary to the Vollum strain, deletion of the bslA gene fully attenuated the ∆pXO2 strain. Though the Vollum∆pXO2 cannot serve as a model for B. anthracis pathogenicity in rabbits, deletion of the bslA gene prevents central nervous system (CNS) infections, possibly leading to the generation of a safer vaccine.
Highlights
Bacillus anthracis is the etiological cause of anthrax
We studied the pathogenicity of a fully virulent Vollum strain of B. anthracis in rabbits and Guinea pigs [23], and demonstrated that, in these two models, meningitis could be detected in animals that succumbed to the infection [24,25,26], as it was previously only reported for humans and nonhuman primates (NHP) [27,28,29]
Since the Vollum∆pXO2 is similar to the Sterne vaccine strain, we tested the pathogenicity of this strain by high-dose spore infection
Summary
Bacillus anthracis is the etiological cause of anthrax. It is a gram-positive spore-forming bacillus, naturally infecting herbivores in farms and wildlife [1,2]. Humans contract anthrax by contact with diseased animals and consumption of contaminated animal products, usually leading to contact of spores or bacteria with skin lesions or the digestive tract, respectively [3]. The third and rarest route of infection is spore inhalation [3], rarely documented in natural outbreaks of the last six decades [5,6]. Inhalational anthrax was the major cause of death in the last two major events of spore release in the United States [7] and Soviet Union [8], be it intentional or accidental release. B. anthracis’ pathogenicity depends on the presence of two major classes of virulence factors, toxins and capsule, encoded by the pXO1 and pXO2 plasmids
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