Abstract
The pathogenicity of Bacillus anthracis, a gram-positive spore-forming bacterium, mainly depends on two plasmid-encoded virulence factors: a poly-gamma-D-glutamate capsule and two toxins. Bioluminescence imaging was used to follow in real-time B. anthracis population dynamics during cutaneous and inhalational infection with bacteria expressing either toxins or capsule. B. anthracis spores were shown to germinate and establish infection at the initial site of inoculation in both routes of infection. Encapsulated B. anthracis then progress to the draining lymph node, spleen, lung, and ultimately the blood. In contrast, toxinogenic non-encapsulated bacteria are initially confined for a prolonged period to the initial site of infection, and then progress to the draining lymph node, and late in the infection, to the kidneys, and frequently the gastrointestinal tract; there is minimal colonization of the spleen. Bioluminescence imaging was also applied to real-time visualization of the effects of immunisation with toxin. We identified the group IIA secretory phospholipase A2 (sPLA2-IIA) as a key anthracidal effector of host innate defense. Transgenic mice expressing human sPLA2-IIA are protected against anthrax and in vivo administration of sPLA2-IIA significantly protects sPLA2-IIA-deficient mice against B. anthracis infection. The potential of this enzyme as a natural therapeutic agent in adjunction to current therapy for treating anthrax is discussed.
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Candela, T. & Fouet, A. (2005) Bacillus anthracis CapD, belonging to the gamma-glutamyltranspeptidase family, is required for the covalent anchoring of capsule to peptidoglycan. Mol Microbiol, 57, 71726.
Candela, T. & Fouet, A. (2006) Poly-gamma-glutamate in bacteria. Mol Microbiol, 60, 1091–8.
Glomski, I. J., Piris-Gimenez, A., Huerre, M., Mock, M. & Goossens, P. L. (2007a) Primary involvement of pharynx and peyer’s patch in inhalational and intestinal anthrax. PLoS Pathog, 3, e76.
Glomski, I. J., Corre, J. P., Mock, M. & Goossens, P. L. (2007b) Noncapsulated toxinogenic Bacillus anthracis presents a specific growth and dissemination pattern in naive and protective antigen-immune mice. Infect Immun, 75, 4754–61.
Glomski, I. J., Corre, J. P., Mock, M. & Goossens, P. L. (2007c) Cutting edge: IFN-gamma-producing CD4 T lymphocytes mediate spore-induced immunity to capsulated Bacillus anthracis. J Immunol, 178, 2646–50.
Keppie, J., Smith, H. & Harris-Smith, P. W. (1953) The chemical basis of the virulence of Bacillus anthracis. II. Some biological properties of bacterial products. Br J Exp Pathol, 34, 486–96.
Laughlin, E. M., Miller, J. D., James, E., Fillos, D., Ibegbu, C. C., Mittler, R. S., Akondy, R., Kwok, W., Ahmed, R. & Nepom, G. (2007) Antigen-specific CD4+ T cells recognize epitopes of protective antigen following vaccination with an anthrax vaccine. Infect Immun, 75, 1852–60.
Leppla, S. H., Robbins, J. B., Schneerson, R. & Shiloach, J. (2002) Development of an improved vaccine for anthrax. J Clin Invest, 110, 141–4.
Mock, M. & Fouet, A. (2001) Anthrax. Annu Rev Microbiol, 55, 647–71.
Piris-Giménez, A., Corre, J. P., Jouvion, G., Candela, T., Khun, H. & Goossens, P. L. (2009) Encapsulated Bacillus anthracis interacts closely with liver endothelium. J Infect Dis, 200, 1381–9.
Piris-Giménez, A., Paya, M., Lambeau, G., Chignard, M., Mock, M., Touqui, L. & Goossens, P. L. (2005). In vivo protective role of human group IIA phospholipase A2 against experimental anthrax. J Immunol, 175, 6786–91.
Piris-Gimenez, A., Wu, Y. Z., Paya, M., Delclaux, C., Touqui, L. & Goossens, P. L. (2004) High bactericidal efficiency of type IIA phospholipase A2 against Bacillus anthracis and inhibition of its secretion by the lethal toxin. J Immunol, 173, 521–30.
Raymond, B., Leduc, D., Ravaux, L., Le Goffic, R., Candela, T., Raymondjean, M., Goossens, P. L., & Touqui, L. (2007) Edema toxins impairs anthracidal phospholipase A2 expression by alveolar macrophages. PLoS Pathog, 3, e187.
Raymond, B., Ravaux, L., Mémet, S., Wu, Y. Z., Sturny-Leclère, A., Leduc, D., Denoyelle, C., Goossens, P. L., Payá, M., Raymondjean, M. & Touqui, L. (2009) Anthrax lethal toxin down-regulates type-IIA secreted phospholipase A2 expression through MAPK/NF-kappaB inactivation. Biochem Pharmacol, http://dx.doi.org/10.1016/j.bcp.2009.11.023
Scorpio, A., Chabot, D. J., Day, W. A. et al. (2007) Poly-gamma-glutamate capsule-degrading enzyme treatment enhances phagocytosis and killing of encapsulated Bacillus anthracis. Antimicrob Agents Chemother, 51, 215–22.
Tournier, J. N., Quesnel-Hellmann, A., Cleret, A. & Vidal, D. R. (2007) Contribution of toxins to the pathogenesis of inhalational anthrax. Cell Microbiol 9, 555–65.
Welkos, S. L. & Friedlander, A. M. (1988) Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice. Microb Pathog, 5, 127–39.
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Goossens, P.L., Glomski, I.J., Touqui, L., Mock, M. (2010). Dynamics of Bacillus anthracis Infection and Control Mechanisms. 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_3
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DOI: https://doi.org/10.1007/978-90-481-9054-6_3
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