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Toxin-deficient Mutants of Bacillus Anthracis Are Lethal in a Murine Model for Pulmonary Anthrax

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Journal Infect Immun
Date 2006 Aug 23
PMID 16923785
Citations 45
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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 those of the parent strain. Mutants lacking one or more of the structural genes for the toxin proteins, i.e., protective antigen, lethal factor, and edema factor, disseminated from the lung to the spleen at rates similar to that of the virulent parental strain. The 50% lethal dose (LD50) and mean time to death (MTD) of the mutants did not differ significantly from those of the parent. The LD50s or MTDs were also unaffected relative to those of 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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References
1.
Pezard C, Berche P, Mock M . Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun. 1991; 59(10):3472-7. PMC: 258908. DOI: 10.1128/iai.59.10.3472-3477.1991. View

2.
Bourgogne A, Drysdale M, Hilsenbeck S, Peterson S, Koehler T . Global effects of virulence gene regulators in a Bacillus anthracis strain with both virulence plasmids. Infect Immun. 2003; 71(5):2736-43. PMC: 153248. DOI: 10.1128/IAI.71.5.2736-2743.2003. View

3.
Ascenzi P, Visca P, Ippolito G, Spallarossa A, Bolognesi M, Montecucco C . Anthrax toxin: a tripartite lethal combination. FEBS Lett. 2002; 531(3):384-8. DOI: 10.1016/s0014-5793(02)03609-8. View

4.
Moayeri M, Haines D, Young H, Leppla S . Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. J Clin Invest. 2003; 112(5):670-82. PMC: 182199. DOI: 10.1172/JCI17991. View

5.
Moayeri M, Leppla S . The roles of anthrax toxin in pathogenesis. Curr Opin Microbiol. 2004; 7(1):19-24. DOI: 10.1016/j.mib.2003.12.001. View