1887

Abstract

Antibodies (Abs) to the protective antigen (PA) component of the anthrax toxins have anti-spore as well as anti-toxin activities. Anti-PA antisera and purified anti-PA Abs enhance the phagocytosis by murine-derived macrophages (MQs) of spores of the Ames and Sterne strains and retard the germination of extracellular spores . The fate after phagocytosis of untreated and anti-PA-treated spores was further studied in culture medium that supported phagocytosis without stimulating spore germination (Dulbecco's minimal essential medium with horse serum 10%). The spores germinated within cells of primary peritoneal murine MQs (C3H/HeN) and MQs of the RAW264.7 MQ-like cell line; germination was associated with a rapid decline in spore viability. Exposure of MQs to inhibitors of phago-endosomal acidification (bafilomycin A and chloroquine) reduced the efficiency of MQ killing and allowed outgrowth and replication of the organisms. Treatment of spores with anti-PA Abs stimulated their phagocytosis and was associated with enhanced MQ killing of the spores. The enhanced killing of spores correlated with the greater extent of germination of anti-PA-treated spores after phagocytosis. A PA null mutant of the Ames strain exhibited none of the effects associated with anti-PA Ab treatment of the parental strain. Thus, the anti-PA Ab-specific immunity induced by vaccines has anti-spore activities and its role in impeding the early stages of infection with needs to be assessed.

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2002-10-01
2019-11-22
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References

  1. Ivins BE, Fellows PF, Pitt MLM.et al. Efficacy of a standard human anthrax vaccine against Bacillus anthracis aerosol spore challenge in rhesus monkeys. Salisbury Med Bull 1996;; Suppl 87: 125–126.
    [Google Scholar]
  2. Pitt MLM, Ivins BE, Estep JE, Farchaus J, Friedlander AM. Comparison of the efficacy of purified protective antigen and MDPH to protect non-human primates from inhalation anthrax. Salisbury Med Bull 1996;; Suppl 87: 130.
    [Google Scholar]
  3. Pitt MLM, Little S, Ivins BE.et al. In vitro correlate of immunity in an animal model of inhalational anthrax. J Appl Microbiol 1999;; 87: 304. [CrossRef]
    [Google Scholar]
  4. Pitt MLM, Little SF, Ivins BE.et al. In vitro correlate of immunity in a rabbit model of inhalational anthrax. Vaccine 2001;; 19: 4768–4773.[CrossRef]
    [Google Scholar]
  5. Reuveny S, White MD, Adar YY.et al. Search for correlates of protective immunity conferred by anthrax vaccine. Infect Immun 2001;; 69: 2888–2893.[CrossRef]
    [Google Scholar]
  6. Stepanov AV, Marinin LI, Pomerantsev AP, Staritsin NA. Development of novel vaccines against anthrax in man. J Biotechnol 1996;; 44: 155–160.[CrossRef]
    [Google Scholar]
  7. Welkos S, Little S, Friedlander A, Fritz D, Fellows P. The role of antibodies to Bacillus anthracis and anthrax toxin components in inhibiting the early stages of infection by anthrax spores. Microbiology 2001;; 147: 1677–1685.
    [Google Scholar]
  8. Pezard C, Berche P, Mock M. Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun 1991;; 59: 3472–3477.
    [Google Scholar]
  9. Pezard C, Duflot E, Mock M. Construction of Bacillus anthracis mutant strains producing a single toxin component. J Gen Microbiol 1993;; 139: 2459–2463.[CrossRef]
    [Google Scholar]
  10. Leighton TJ, Doi RH. The stability of messenger ribonucleic acid during sporulation in Bacillus subtilis. J Biol Chem 1971;; 246: 3189–3195.
    [Google Scholar]
  11. Welkos SL, Trotter RW, Becker DM, Nelson GO. Resistance to the Sterne strain of B. anthracis: phagocytic cell responses of resistant and susceptible mice. Microb Pathog 1989;; 7: 15–35.[CrossRef]
    [Google Scholar]
  12. Guidi-Rontani C, Levy M, Ohayon H, Mock M. Fate of germinated Bacillus anthracis spores in primary murine macrophages. Mol Microbiol 2001;; 42: 931–938.[CrossRef]
    [Google Scholar]
  13. Lindgren SW, Stojiljkovic I, Heffron F. Macrophage killing is an essential virulence mechanism of Salmonella typhimurium. Proc Natl Acad Sci USA 1996;; 93: 4197–4201.[CrossRef]
    [Google Scholar]
  14. Ivins BE, Welkos SL. Cloning and expression of the Bacillus anthracis protective antigen gene in Bacillus subtilis. Infect Immun 1986;; 54: 537–542.
    [Google Scholar]
  15. Worsham PL, Sowers MR. Isolation of an asporogenic (spoOA) protective antigen-producing strain of Bacillus anthracis. Can J Microbiol 1999;; 45: 1–8.[CrossRef]
    [Google Scholar]
  16. Friedlander AM. Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J Biol Chem 1986;; 261: 7123–7126.
    [Google Scholar]
  17. Gordon VM, Leppla SH, Hewlett EL. Inhibitors of receptor-mediated endocytosis block the entry of Bacillus anthracis adenylate cyclase toxin but not that of Bordetella pertussis adenylate cyclase toxin. Infect Immun 1988;; 56: 1066–1069.
    [Google Scholar]
  18. Heinzen RA, Scidmore MA, Rockey DD, Hackstadt T. Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis. Infect Immun 1996;; 64: 796–809.
    [Google Scholar]
  19. Leppla SH. Anthrax toxin. In: Aktories K, Just I (eds) Bacterial protein toxins. Handbook of experimental pharmacology, vol 145. Berlin, Springer-Verlag. 2000:; 445–472.
  20. Ménard A, Altendorf K, Breves D, Mock M, Montecucco C. The vacuolar ATPase proton pump is required for the cytotoxicity of Bacillus anthracis lethal toxin. FEBS Lett 1996;; 386: 161–164.[CrossRef]
    [Google Scholar]
  21. Barnes JM. The development of anthrax following the administration of spores by inhalation. Br J Exp Pathol 1947;; 28: 385–394.
    [Google Scholar]
  22. Dixon TC, Meselson M, Guillemin J, Hanna PC. Anthrax. N Engl J Med 1999;; 341: 815–826.[CrossRef]
    [Google Scholar]
  23. Dixon TC, Fadl AA, Koehler TM, Swanson JA, Hanna PC. Early Bacillus anthracis-macrophage interactions: intracellular survival and escape. Cellular Microbiol 2000;; 2: 453–463.[CrossRef]
    [Google Scholar]
  24. Guidi-Rontani C, Weber-Levy M, Labruyere E, Mock M. Germination of Bacillus anthracis spores within alveolar macrophages. Mol Microbiol 1999;; 31: 9–17.[CrossRef]
    [Google Scholar]
  25. Hanna PC, Ireland JAW. Understanding Bacillus anthracis pathogenesis. Trends Microbiol 1999;; 7: 180–182.[CrossRef]
    [Google Scholar]
  26. Lincoln RE, Rhian MA, Klein F, Fernelius A. Pathogenesis as related to the physiological state of anthrax spores and cell. In: Halvorson HO (ed) Spores II. Minneapolis, Burgess Publishing Co. 1961:; 255–275.
  27. Metchnikoff E. Immunity in infective diseases. Cambridge, Cambridge University Press. 1905.
  28. Ross JM. The pathogenesis of anthrax following the administration of spores by the respiratory route. J Pathol Bacteriol 1957;; 73: 485–494.[CrossRef]
    [Google Scholar]
  29. Young GA, Zelle RE, Lincoln RE. Respiratory pathogenicity of Bacillus anthracis spores.I. Methods of study and observations on pathogenesis. J Infect Dis 1946;; 79: 233–246.[CrossRef]
    [Google Scholar]
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