Abstract
The polyglutamic acid capsule of Bacillus anthracis is a well-established virulence factor, conferring antiphagocytic properties on the bacillus. We have shown that the capsule also confers partial resistance to killing by human defensins. In our research we targeted the anthrax capsule for developing medical countermeasures, first using the capsule as a vaccine, similar to successful efforts with other bacteria, and secondly, by developing a novel therapeutic against the capsule. Our experiments showed that a capsule vaccine is protective in the mouse model and its efficacy could be enhanced by conjugation to a protein carrier. In initial experiments using high challenge doses, a capsule conjugate vaccine was not protective in rabbits but did show some protection in nonhuman primates. This suggests it may be useful as an addition to a protective antigen-based vaccine. We are also developing the use of the B. anthracis capsule-depolymerizing enzyme, CapD, as a therapeutic. We demonstrated that in vitro treatment of the encapsulated anthrax bacillus with CapD enzymatically removed the capsule from the bacterial surface making it susceptible to phagocytic killing. Initial experiments in vivo showed that CapD could be used successfully to treat experimental anthrax infections. Such a novel approach to target the capsule virulence factor might be of value in the treatment of infections due to antibiotic-resistant strains.
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Acknowledgments
I thank the Defense Threat Reduction Agency for funding our research and Donald Chabot for help with several of the figures. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U.S. Army.
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Friedlander, A.M. (2010). The Anthrax Capsule: Role in Pathogenesis and Target for Vaccines and Therapeutics. In: Shafferman, A., Ordentlich, A., Velan, B. (eds) The Challenge of Highly Pathogenic Microorganisms. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9054-6_1
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DOI: https://doi.org/10.1007/978-90-481-9054-6_1
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