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Infect. Immun. doi:10.1128/IAI.00575-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Non-capsulated toxinogenic Bacillus anthracis present a specific growth and dissemination pattern in naive and PA-immune mice

Ian J. Glomski, Jean-Philippe Corre, Michèle Mock, and Pierre L. Goossens*

Institut Pasteur, Unité des Toxines et Pathogénie Bactérienne, Paris, F-75015, France; CNRS, URA 2172, Paris, F-75015, France

* To whom correspondence should be addressed. Email: pierre.goossens{at}pasteur.fr.


   Abstract

Bacillus anthracis is a spore-forming bacterium that causes anthrax. B. anthracis has three major virulence factors; lethal toxin, edema toxin, and a poly-{gamma}-D-glutamic acid capsule. The toxins modulate host immune responses and the capsule inhibits phagocytosis. With the goal of increasing safety, decreasing security concerns, and taking advantage of mammalian genetic tools and reagents, mouse models of B. anthracis infection have been developed using attenuated bacteria that produce toxins but no capsule. While these models have been useful in studying both toxinogenic infections and anti-toxin vaccine efficacy, we questioned whether eliminating capsule changed bacterial growth and dissemination characteristics. Thus, the progression of infection by toxinogenic non-capsulated B. anthracis was analyzed and compared to previously reported non-toxinogenic capsulated bacteria using in vivo bioluminescent imaging. The influence of immunization with the toxin component, protective antigen (PA), on the development of infection was also examined. The toxinogenic non-capsulated bacteria were initially confined to the cutaneous site of infection. Bacteria then progressed to the draining lymph node, and finally, late in the infection, to the lungs, kidneys, and frequently the gastrointestinal tract. There was minimal colonization of the spleen. PA immunization reduced bacterial growth from the outset and limited infection to the site of inoculation. These in vivo observations show that dissemination by toxinogenic non-capsulated strains differ markedly from non-toxinogenic capsulated strains. Additionally, PA-immunization counters bacterial growth and dissemination in vivo from the onset of infection.




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