Analysis of a Novel Spore Antigen in Bacillus anthracis That Contributes to Spore Opsonization

摘要

The importance of Bacillus anthracis as an agent of bioterrorism has been well established. An understanding of both the pathogenesis and the host response is required to elucidate approaches to more rapidly detect and effectively prevent or treat anthrax. Current vaccine strategies are focused primarily on production of antibodies against the protective antigen component of the anthrax toxins, which are secreted by the bacilli. It has been shown that an immune response to spore antigens can enhance vaccine efficacy. The goal of this study was to identify new spore-associated candidates for a multi- component anthrax vaccine, particularly those that are potentially able to impede early events in spore germination and subsequent toxin production. A spore-associated protein was identified that was specific to the B. cereus group of bacteria and referred to as spore opsonization-associated antigen A (SoaA). Immunoelectron microscopy localized this protein to the undercoat layer of the dormant spore. Although our data suggested that SoaA was found below the coat layers of the ungerminated spore, SoaA was involved in the interaction of spores with macrophages shortly after infection. To investigate further the specific properties of the SoaA protein, the soaA gene was inactivated in the B. anthracis Ames strain. The presence of SoaA in the Ames strain of B. anthracis appeared to increase the phagocytic uptake of the spores in the presence of anti-spore antibodies, since, unlike the wild-type strain, the soaA::Kan strain was not readily opsonized by anti-spore antibodies. While the mutant spores retained characteristic resistance properties in vitro, the soaA::Kan mutant strain was significantly less suited for survival in a guinea pig challenge model of anthrax infection.