Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits

The major virulence factor of Bacillus anthracis is the tripartite anthrax toxin, comprising the protective antigen (PA), lethal factor (LF) and edema factor (EF). The LF of B. anthracis is a metalloprotease that has been shown to play an important role in pathogenicity. Deletion of this gene (lef) in the Sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was reported to be as dramatic as the deletion of PA. We evaluated the effect on pathogenicity of the lef deletion in the fully virulent Vollum strain in guinea pigs and NZW rabbits by either subcutaneous injection or intranasal instillation. In guinea pigs, no major differences between the mutant strain and the wild type could be detected in the LD(50) or mean time to death values. On the other hand, the lef deletion caused death of 50-70% of all rabbits infected with the mutant spores at doses equivalent or higher than the wild type LD(50). The surviving rabbits, which were infected with spore doses higher than the wild type LD(50), developed a protective immune response that conferred resistance to challenge with the wild type strain. These findings may indicate that the mutant lacking the LF is capable of host colonization which causes death in 50-70% of the animals and a protective immune response in the others. These results indicate that unlike the data obtained in mice, the LF mutation does not abolish B. anthracis pathogenicity.