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Infect. Immun. doi:10.1128/IAI.00719-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Toxin-Deficient Mutants of Bacillus anthracis are Lethal in a Murine Model for Pulmonary Anthrax

Department of Molecular Genetics and Microbiology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131, USA; Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131, USA; Lovelace Respiratory Research Institute, Albuquerque, NM 87131, USA; Department of Pathology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131, USA; Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Houston, Texas 77030, U.S.A; Departments of Internal Medicine and Molecular Genetics and Microbiology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131, USA

^* To whom correspondence should be addressed. Email: Clyons{at}salud.unm.edu.

	Abstract

Bacillus anthracis, the etiologic agent of anthrax, produces at least three primary virulence factors: lethal toxin, edema toxin, and a capsule. The capsule is absolutely required for dissemination and lethality in a murine model of inhalation anthrax, yet the roles for the toxins during infection are ill-defined. We show in a murine model that when spores of specific toxin-null mutants are introduced into the lung, dissemination and lethality are comparable to the parent strain. Mutants lacking one or more of the structural genes for the toxin proteins, protective antigen, lethal factor, and edema factor, disseminated from the lung to the spleen at rates similar to the virulent parental strain. The LD₅₀ dose and mean time to death (MTD) of the mutants did not differ significantly from the parent. The LD₅₀ or MTD values were also unaffected relative to the parent strain when mice were inoculated intravenously with vegetative cells. Nonetheless, histopathological examination of tissues revealed subtle but distinct differences in infections by the parent compared to some toxin mutants, suggesting that the host response is affected by toxin proteins synthesized during infection.

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