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Animal Models for the Pathogenesis, Treatment, and Prevention of Infection by

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  • Authors: Susan Welkos1, Joel Bozue2, Nancy Twenhafel3, Christopher Cote4
  • Editors: Patrick Eichenberger5, Adam Driks6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702; 2: Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702; 3: Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702; 4: Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702; 5: New York University, New York, NY; 6: Loyola University Medical Center, Maywood, IL
  • Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.TBS-0001-2012
  • Received 08 June 2012 Accepted 28 December 2014 Published 20 February 2015
  • Susan Welkos, susan.welkos@us.army.mil
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  • Abstract:

    This article reviews the characteristics of the major animal models utilized for studies on and highlights their contributions to understanding the pathogenesis and host responses to anthrax and its treatment and prevention. Advantages and drawbacks associated with each model, to include the major models (murine, guinea pig, rabbit, nonhuman primate, and rat), and other less frequently utilized models, are discussed. Although the three principal forms of anthrax are addressed, the main focus of this review is on models for inhalational anthrax. The selection of an animal model for study is often not straightforward and is dependent on the specific aims of the research or test. No single animal species provides complete equivalence to humans; however, each species, when used appropriately, can contribute to a more complete understanding of anthrax and its etiologic agent.

  • Citation: Welkos S, Bozue J, Twenhafel N, Cote C. 2015. Animal Models for the Pathogenesis, Treatment, and Prevention of Infection by . Microbiol Spectrum 3(1):TBS-0001-2012. doi:10.1128/microbiolspec.TBS-0001-2012.

References

1. Davies JC. 1983. A major epidemic of anthrax in Zimbabwe. Part II. Cent Afr J Med 29:8–12. [PubMed]
2. De Vos V. 1990. The ecology of anthrax in the Kruger National Park, South Africa. Salisbury Med Bull 87:26–30.
3. Turnbull P. 2008. Anthrax in Humans and Animals, 4th ed. WHO Press, Geneva, Switzerland.
4. Brachman P, Friedlander A, Grabenstein J. 2008. Anthrax vaccine, p 111–126. In Plotkin S, Orenstein W, Offit P (ed), Vaccines, 5th ed. Saunders Elsevier Press, Philadelphia, PA.
5. Friedlander A, Little S, Gurwith M. 2009. Anthrax vaccines, p 851–863. In Levine MM, Dougan G, Good MF, Liu MA (ed), New Generation Vaccines, 4th ed. Informa Healthcare, New York, NY.
6. Laforce FM. 1978. Woolsorters' disease in England. Bull N Y Acad Med 54:956–963. [PubMed]
7. Purcell BK, Worsham PL, Friedlander AM. 2007. Anthrax, p 69–90. In Dembek ZF (ed), Medical Aspects of Biological Warfare. Borden Institute, Walter Reed Army Medical Center, Washington, DC.
8. Plotkin SA, Brachman PS, Utell M, Bumford FH, Atchison MM. 1960. An epidemic of inhalation anthrax, the first in the twentieth century. I. Clinical features. Am J Med 29:992–1001. [PubMed][CrossRef]
9. Cieslak TJ, Henretig FM. 2001. Medical consequences of biological warfare: the Ten Commandments of management. Mil Med 166:11–12. [PubMed]
10. Bell DM, Kozarsky PE, Stephens DS. 2002. Clinical issues in the prophylaxis, diagnosis, and treatment of anthrax. Emerg Infect Dis 8:222–225. [PubMed][CrossRef]
11. Bell JH, Fee E, Brown TM. 2002. Anthrax and the wool trade. 1902. Am J Public Health 92:754–757. [PubMed][CrossRef]
12. Dixon TC, Meselson M, Guillemin J, Hanna PC. 1999. Anthrax. N Engl J Med 341:815–826. [PubMed][CrossRef]
13. Guarner J, Del Rio C. 2011. Pathology, diagnosis, and treatment of anthrax in humans, p 251–268. In Bergman NH (ed), Bacillus anthracis and anthrax. John Wiley & Sons, Inc., Hoboken, NJ.
14. Holty JE, Bravata DM, Liu H, Olshen RA, McDonald KM, Owens DK. 2006. Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med 144:270–280. [PubMed][CrossRef]
15. Holty JE, Kim RY, Bravata DM. 2006. Anthrax: a systematic review of atypical presentations. Ann Emerg Med 48:200–211. [PubMed][CrossRef]
16. Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm MT, Parker G, Perl TM, Russell PK, Tonat K. 2002. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 287:2236–2252. [PubMed][CrossRef]
17. Beatty ME, Ashford DA, Griffin PM, Tauxe RV, Sobel J. 2003. Gastrointestinal anthrax: review of the literature. Arch Intern Med 163:2527–2531. [PubMed][CrossRef]
18. Mock M, Fouet A. 2001. Anthrax. Annu Rev Microbiol 55:647–671. [PubMed][CrossRef]
19. Grinberg LM, Abramova FA, Yampolskaya OV, Walker DH, Smith JH. 2001. Quantitative pathology of inhalational anthrax I: quantitative microscopic findings. Mod Pathol 14:482–495. [PubMed][CrossRef]
20. ProMED-mail. 2005. Anthrax, human-Russia (Northern Osetia). http://www.promedmail.org. Accessed 14 September 2005.
21. Mayo L, Dionne-Odom J, Talbot EA, Adamski C, Bean C, Daly ER. 2009. Gastrointestinal anthrax after an animal-hide drumming event – New Hampshire and Massachusetts, 2009. MMWR Morb Mortal Wkly Rep 59:872–877.
22. ProMED-mail. 2009. Anthrax, human, 2006-UK. http://www.promedmail.org. Accessed 21 April 2009.
23. ProMED-mail. 2010. Anthrax-United Kingdom: (Scotland). http://www.promedmail.org. Accessed 29 January 2010.
24. Ringertz SH, Hoiby EA, Jensenius M, Maehlen J, Caugant DA, Myklebust A, Fossum K. 2000. Injectional anthrax in a heroin skin-popper. Lancet 356:1574–1575. [PubMed][CrossRef]
25. Walsh J, Fraser G, Hunt B, Husband B, Nalluswami K, Pollard K. 2006. Inhalation anthrax associated with dried animal hides – Pennsylvania and New York City, 2006. MMWR Morb MortalWkly Rep 55:280–282. [PubMed]
26. Abramova AA, Grinberg LM. 1993. Pathology of anthrax sepsis according to materials of the infectious outbreak in 1979 in Sverdlovsk (microscopic changes). Arkh Patol 55:18–23. (In Russian.) [PubMed]
27. Guarner J, Jernigan JA, Shieh WJ, Tatti K, Flannagan LM, Stephens DS, Popovic T, Ashford DA, Perkins BA, Zaki SR. 2003. Pathology and pathogenesis of bioterrorism-related inhalational anthrax. Am J Pathol 163:701–709. [PubMed][CrossRef]
28. Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M, Tapper M, Fisk TL, Zaki S, Popovic T, Meyer RF, Quinn CP, Harper SA, Fridkin SK, Sejvar JJ, Shepard CW, McConnell M, Guarner J, Shieh WJ, Malecki JM, Gerberding JL, Hughes JM, Perkins BA. 2001. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis 7:933–944. [PubMed][CrossRef]
29. Keim P, Smith KL, Keys C, Takahashi H, Kurata T, Kaufmann A. 2001. Molecular investigation of the Aum Shinrikyo anthrax release in Kameido, Japan. J Clin Microbiol 39:4566–4567. [PubMed][CrossRef]
30. Meselson M, Guillemin J, Hugh-Jones M, Langmuir A, Popova I, Shelokov A, Yampolskaya O. 1994. The Sverdlovsk anthrax outbreak of 1979. Science 266:1202–1208. [PubMed][CrossRef]
31. Zilinskas RA. 1997. Iraq's biological weapons. The past as future? JAMA 278:418–424. [PubMed][CrossRef]
32. Koch R. 1938. Beitrage zur Biologie der Pflanzen. Med Classics 2:787–820.
33. Pasteur L. 1881. De l'attenuation des virus et de leur retour à la virulence. C R Acad Sci Agric Bulg 1881, 92:429–435.
34. Pasteur L, Chamberland, Roux. 2002. Summary report of the experiments conducted at Pouilly-le-Fort, near Melun, on the anthrax vaccination, 1881. Yale J Biol Med 75:59–62. [PubMed]
35. Turnbull PCB, Shadomy SV. 2011. Anthrax from 5000 BC to AD2010, p 1–16. In Bergman NH (ed), Bacillus anthracis and anthrax. John Wiley & Sons, Inc., Hoboken, NJ. [PubMed]
36. Buchner H, Merkel F, Enderlen E. 1888. Arch Hyg (Berlin) 8:145.
37. Young GA, Zelle MR, Lincoln RE. 1946. Respiratory pathogenecity of Bacillus anthracis spores. I. Methods of study and observation on pathogenesis. J Infect Dis 79:233–246. [PubMed][CrossRef]
38. Barnes JM. 1947. The development of anthrax following the administration of spores by inhalation. Br J Exp Pathol 28:385–393.
39. Ross JM. 1957. The pathogenesis of anthrax following the administration of spores by the respiratory route. J Pathol Bacteriol 73:485–494. [CrossRef]
40. Albrink WS, Goodlow RJ. 1959. Experimental inhalation anthrax in the chimpanzee. Am J Pathol 35:1055–1065. [PubMed]
41. Henderson DW, Peacock S, Belton FC. 1956. Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. J Hyg (Lond) 54:28–36. [PubMed][CrossRef]
42. Lincoln RE, Hodges DR, Klein F, Mahlandt BG, Jones WI, Jr, Haines BW, Rhian MA, Walker JS. 1965. Role of the lymphatics in the pathogenesis of anthrax. J Infect Dis 115:481–494. [PubMed][CrossRef]
43. Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH. 1993. Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979. Proc Natl Acad Sci USA 90:2291–2294. [PubMed][CrossRef]
44. Albrink WS, Brooks SM, Biron RE, Kopel M. 1960. Human inhalation anthrax. A report of three fatal cases. Am J Pathol 36:457–471. [PubMed]
45. Brachman PS, Plotkin SA, Bumford FH, Atchison MM. 1960. An epidemic of inhalation anthrax: the first in the twentieth century. II. Epidemiology. Am J Hyg 72:6–23. [PubMed]
46. Grinberg LM, Abramova AA. 1993. Pathology of anthrax sepsis according to materials of the infectious outbreak in 1979 in Sverdlovsk (various aspects of morpho-, patho- and thanatogenesis). Arkh Patol 55:23–26. (In Russian.) [PubMed]
47. Bail O. 1914. Changes to bacteria inside the animal body. IX. Regarding the correlation between capsule formation, spore formation and infectiousness of the anthrax bacillus. Zentb Bakteriol 75:159–173.
48. Shlyakhov EN, Rubinstein E. 1994. Human live anthrax vaccine in the former USSR. Vaccine 12:727–730. [PubMed][CrossRef]
49. Turnbull PC. 1991. Anthrax vaccines: past, present and future. Vaccine 9:533–539. [PubMed][CrossRef]
50. Keppie J, Smith H, Harris-Smith PW. 1953. The chemical basis of the virulence of bacillus anthracis. II. Some biological properties of bacterial products. Br J Exp Pathol 34:486–496. [PubMed]
51. Keppie J, Smith H, Harris-Smith PW. 1955. The chemical basis of the virulence of Bacillus anthracis. III. The role of the terminal bacteraemia in death of guinea-pigs from anthrax. Br J Exp Pathol 36:315–322. [PubMed]
52. Evans DG, Shoesmith JG. 1954. Production of toxin by Bacillus anthracis. Lancet 263:136. doi:10.1016/S0140-6736(54)90984-8. [CrossRef]
53. Lincoln RE, Walker JS, Klein F, Rosenwald AJ, Jones WI, Jr. 1967. Value of field data for extrapolation in anthrax. Fed Proc 26:1558–1562. [PubMed]
54. Abalakin VA, Cherkasskii BL. 1978. Use of inbred mice as a model for the indication and differentiation of Bacillus-anthracis strains. Zh Mikrobiol Epidemiol Immunobiol 146–147. (In Russian.) [PubMed]
55. Welkos SL, Keener TJ, Gibbs PH. 1986. Differences in susceptibility of inbred mice to Bacillus anthracis. Infect Immun 51:795–800. [PubMed]
56. Coleman ME, Thran B, Morse SS, Hugh-Jones M, Massulik S. 2008. Inhalation anthrax: dose response and risk analysis. Biosecur Bioterror 6:147–160. [PubMed][CrossRef]
57. Bartrand TA, Weir MH, Haas CN. 2008. Dose-response models for inhalation of Bacillus anthracis spores: interspecies comparisons. Risk Anal 28:1115–1124. [PubMed][CrossRef]
58. Brookmeyer R, Johnson E, Barry S. 2005. Modelling the incubation period of anthrax. Stat Med 24:531–542. [PubMed][CrossRef]
59. Cohen M, Whalen T. 2007. Implications of low level human exposure to respirable B. anthracis. Appl Biosafety 12:109–115.
60. Glassman HN. 1966. Industrail inhalational anthrax. Discussion. Bacteriol Rev 30:657–659. [PubMed]
61. Webb GF, Blaser MJ. 2002. Mailborne transmission of anthrax: Modeling and implications. Proc Natl Acad Sci USA 99:7027–7032. [PubMed][CrossRef]
62. Wilkening DA. 2006. Sverdlovsk revisited: modeling human inhalation anthrax. Proc Natl Acad Sci USA 103:7589–7594. [PubMed][CrossRef]
63. Wilkening DA. 2008. Modeling the incubation period of inhalational anthrax. Med Decis Making 28:593–605. [PubMed][CrossRef]
64. Nelson M, Stagg AJ, Stevens DJ, Brown MA, Pearce PC, Simpson AJ, Lever MS. 2011. Post-exposure therapy of inhalational anthrax in the common marmoset. Int J Antimicrob Agents 38:60–64. [PubMed][CrossRef]
65. Twenhafel NA, Leffel E, Pitt ML. 2007. Pathology of inhalational anthrax infection in the african green monkey. Vet Pathol 44:716–721. [PubMed][CrossRef]
66. Liu S, Miller-Randolph S, Crown D, Moayeri M, Sastalla I, Okugawa S, Leppla SH. 2010. Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice. Cell Host Microbe 8:455–462. [PubMed][CrossRef]
67. McAllister RD, Singh Y, du Bois WD, Potter M, Boehm T, Meeker ND, Fillmore PD, Anderson LM, Poynter ME, Teuscher C. 2003. Susceptibility to anthrax lethal toxin is controlled by three linked quantitative trait loci. Am J Pathol 163:1735–1741. [PubMed][CrossRef]
68. Moayeri M, Crown D, Newman ZL, Okugawa S, Eckhaus M, Cataisson C, Liu S, Sastalla I, Leppla SH. 2010. Inflammasome sensor Nlrp1b-dependent resistance to anthrax is mediated by caspase-1, IL-1 signaling and neutrophil recruitment. PLoS Pathog 6:e1001222. doi:10.1371/journal.ppat.1001222. [PubMed][CrossRef]
69. Terra JK, Cote CK, France B, Jenkins AL, Bozue JA, Welkos SL, LeVine SM, Bradley KA. 2010. Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b. J Immunol 184:17–20. [PubMed][CrossRef]
70. Watters JW, Dietrich WF. 2001. Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11. Genomics 73:223–231. [PubMed][CrossRef]
71. Yadav JS, Pradhan S, Kapoor R, Bangar H, Burzynski BB, Prows DR, Levin L. 2011. Multigenic control and sex bias in host susceptibility to spore-induced pulmonary anthrax in mice. Infect Immun 79:3204–3215. [PubMed][CrossRef]
72. Hau J. 2008. Animal models for human diseases, p 3–8. In Conn PM (ed), Sourcebook of Models for Biomedical Research. Humana Press, Inc., Towota, NJ. [CrossRef]
73. Phipps AJ, Premanandan C, Barnewall RE, Lairmore MD. 2004. Rabbit and nonhuman primate models of toxin-targeting human anthrax vaccines. Microbiol Mol Biol Rev 68:617–629. [PubMed][CrossRef]
74. Cote CK, Rea KM, Norris SL, van Rooijen N, Welkos SL. 2004. The use of a model of in vivo macrophage depletion to study the role of macrophages during infection with Bacillus anthracis spores. Microb Pathog 37:169–175. [PubMed][CrossRef]
75. Cote CK, van Rooijen N, Welkos SL. 2006. The roles of macrophages and neutrophils in the early host response to Bacillus anthracis spores using a mouse model of infection. Infect Immun 74:469–480. [PubMed][CrossRef]
76. Dumetz F, Jouvion G, Khun H, Glomski IJ, Corre JP, Rougeaux C, Tang WJ, Mock M, Huerre M, Goossens PL. 2011. Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax. Am J Pathol 178:2523–2535. [PubMed][CrossRef]
77. Heine HS, Bassett J, Miller L, Hartings JM, Ivins BE, Pitt ML, Fritz D, Norris SL, Byrne WR. 2007. Determination of antibiotic efficacy against Bacillus anthracis in a mouse aerosol challenge model. Antimicrob Agents Chemother 51:1373–1379. [PubMed][CrossRef]
78. Lyons CR, Lovchik J, Hutt J, Lipscomb MF, Wang E, Heninger S, Berliba L, Garrison K. 2004. Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility. Infect Immun 72:4801–4809. [PubMed][CrossRef]
79. Glomski IJ, Dumetz F, Jouvion G, Huerre MR, Mock M, Goossens PL. 2008. Inhaled non-capsulated Bacillus anthracis in A/J mice: nasopharynx and alveolar space as dual portals of entry, delayed dissemination, and specific organ targeting. Microbes Infect 10:1398–1404. [PubMed][CrossRef]
80. Cleret A, Quesnel-Hellmann A, Vallon-Eberhard A, Verrier B, Jung S, Vidal D, Mathieu J, Tournier JN. 2007. Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route. J Immunol 178:7994–8001. [PubMed][CrossRef]
81. Duong S, Chiaraviglio L, Kirby JE. 2006. Histopathology in a murine model of anthrax. Int J Exp Pathol 87:131–137. [PubMed][CrossRef]
82. Glomski IJ, Corre JP, Mock M, Goossens PL. 2007. Noncapsulated toxinogenic Bacillus anthracis presents a specific growth and dissemination pattern in naive and protective antigen-immune mice. Infect Immun 75:4754–4761. [PubMed][CrossRef]
83. Glomski IJ, Piris-Gimenez A, Huerre M, Mock M, Goossens PL. 2007. Primary involvement of pharynx and Peyer's patch in inhalational and intestinal anthrax. PLoS Pathog 3:e76. doi:10.1371/journal.ppat.0030076. [PubMed][CrossRef]
84. Loving CL, Kennett M, Lee GM, Grippe VK, Merkel TJ. 2007. Murine aerosol challenge model of anthrax. Infect Immun 75:2689–2698. [PubMed][CrossRef]
85. Loving CL, Khurana T, Osorio M, Lee GM, Kelly VK, Stibitz S, Merkel TJ. 2009. Role of anthrax toxins in dissemination, disease progression, and induction of protective adaptive immunity in the mouse aerosol challenge model. Infect Immun 77:255–265. [PubMed][CrossRef]
86. Heninger S, Drysdale M, Lovchik J, Hutt J, Lipscomb MF, Koehler TM, Lyons CR. 2006. Toxin-deficient mutants of Bacillus anthracis are lethal in a murine model for pulmonary anthrax. Infect Immun 74:6067–6074. [PubMed][CrossRef]
87. Welkos SL. 1991. Plasmid-associated virulence factors of non-toxigenic (pX01-) Bacillus anthracis. Microb Pathog 10:183–198. [PubMed][CrossRef]
88. Welkos SL, Vietri NJ, Gibbs PH. 1993. Non-toxigenic derivatives of the Ames strain of Bacillus anthracis are fully virulent for mice: role of plasmid pX02 and chromosome in strain-dependent virulence. Microb Pathog 14:381–388. [PubMed][CrossRef]
89. Friedlander AM, Welkos SL, Ivins BE. 2002. Anthrax vaccines. Curr Top Microbiol Immunol 271:33–60. [PubMed][CrossRef]
90. Ivins BE, Ezzell JW, Jr, Jemski J, Hedlund KW, Ristroph JD, Leppla SH. 1986. Immunization studies with attenuated strains of Bacillus anthracis. Infect Immun 52:454–458. [PubMed]
91. Fellows PF, Linscott MK, Ivins BE, Pitt ML, Rossi CA, Gibbs PH, Friedlander AM. 2001. Efficacy of a human anthrax vaccine in guinea pigs, rabbits, and rhesus macaques against challenge by Bacillus anthracis isolates of diverse geographical origin. Vaccine 19:3241–3247. [PubMed][CrossRef]
92. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Emes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigó R, Guyer M, Hardison RC, Haussler D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK, Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, Levine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mott R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O'Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tesler G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, Lander ES. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562. [PubMed][CrossRef]
93. Haley PJ. 2003. Species differences in the structure and function of the immune system. Toxicology 188:49–71. [PubMed][CrossRef]
94. Mestas J, Hughes CC. 2004. Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738. [PubMed][CrossRef]
95. Mizgerd JP, Skerrett SJ. 2008. Animal models of human pneumonia. Am J Physiol Lung Cell Mol Physiol 294:L387–L398. [PubMed][CrossRef]
96. Deziel MR, Heine H, Louie A, Kao M, Byrne WR, Basset J, Miller L, Bush K, Kelly M, Drusano GL. 2005. Effective antimicrobial regimens for use in humans for therapy of Bacillus anthracis infections and postexposure prophylaxis. Antimicrob Agents Chemother 49:5099–5106. [PubMed][CrossRef]
97. Castelan-Vega J, Corvette L, Sirota L, Arciniega J. 2011. Reduction of immunogenicity of anthrax vaccines subjected to thermal stress, as measured by a toxin neutralization assay. Clin Vaccine Immunol 18:349–351. [PubMed][CrossRef]
98. Little SF, Webster WM, Ivins BE, Fellows PF, Norris SL, Andrews GP. 2004. Development of an in vitro-based potency assay for anthrax vaccine. Vaccine 22:2843–2852. [PubMed][CrossRef]
99. Albrecht MT, Li H, Williamson ED, LeButt CS, Flick-Smith HC, Quinn CP, Westra H, Galloway D, Mateczun A, Goldman S, Groen H, Baillie LW. 2007. Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax. Infect Immun 75:5425–5433. [PubMed][CrossRef]
100. Williamson ED, Duchars MG, Kohberger R. 2010. Predictive models and correlates of protection for testing biodefence vaccines. Expert Rev Vaccines 9:527–537. [PubMed][CrossRef]
101. Beedham RJ, Turnbull PC, Williamson ED. 2001. Passive transfer of protection against Bacillus anthracis infection in a murine model. Vaccine 19:4409–4416. [PubMed][CrossRef]
102. Welkos S, Becker D, Friedlander A, Trotter R. 1989. Pathogenesis and host response to Bacillus anthracis: a mouse model. Salisbury Med Bull 87:49–52.
103. Welkos SL, Friedlander AM. 1988. Pathogenesis and genetic control of resistance to the Sterne strain of Bacillus anthracis. Microb Pathog 4:53–69. [PubMed][CrossRef]
104. Welkos SL, Trotter RW, Becker DM, Nelson GO. 1989. Resistance to the Sterne strain of B. anthracis: phagocytic cell responses of resistant and susceptible mice. Microb Pathog 7:15–35. [PubMed][CrossRef]
105. Harvill ET, Osorio M, Loving CL, Lee GM, Kelly VK, Merkel TJ. 2008. Anamnestic protective immunity to Bacillus anthracis is antibody mediated but independent of complement and Fc receptors. Infect Immun 76:2177–2182. [PubMed][CrossRef]
106. Pickering AK, Osorio M, Lee GM, Grippe VK, Bray M, Merkel TJ. 2004. Cytokine response to infection with Bacillus anthracis spores. Infect Immun 72:6382–6389. [PubMed][CrossRef]
107. Sanz P, Teel LD, Alem F, Carvalho HM, Darnell SC, O'Brien AD. 2008. Detection of Bacillus anthracis spore germination in vivo by bioluminescence imaging. Infect Immun 76:1036–1047. [PubMed][CrossRef]
108. Kang TJ, Basu S, Zhang L, Thomas KE, Vogel SN, Baillie L, Cross AS. 2008. Bacillus anthracis spores and lethal toxin induce IL-1beta via functionally distinct signaling pathways. Eur J Immunol 38:1574–1584. [PubMed][CrossRef]
109. Popov SG, Popova TG, Grene E, Klotz F, Cardwell J, Bradburne C, Jama Y, Maland M, Wells J, Nalca A, Voss T, Bailey C, Alibek K. 2004. Systemic cytokine response in murine anthrax. Cell Microbiol 6:225–233. [PubMed][CrossRef]
110. Harvill ET, Lee G, Grippe VK, Merkel TJ. 2005. Complement depletion renders C57BL/6 mice sensitive to the Bacillus anthracis Sterne strain. Infect Immun 73:4420–4422. [PubMed][CrossRef]
111. Gleiser CA, Berdjis CC, Hartman HA, Gochenour WS. 1963. Pathology of experimental respiratory anthrax in Macaca mulatta. Br J Exp Pathol 44:416–426. [PubMed]
112. Bozue J, Cote CK, Moody KL, Welkos SL. 2007. Fully virulent Bacillus anthracis does not require the immunodominant protein, BclA, for pathogenesis. Infect Immun 75:508–511. [PubMed][CrossRef]
113. Friedlander AM, Welkos SL, Pitt ML, Ezzell JW, Worsham PL, Rose KJ, Ivins BE, Lowe JR, Howe GB, Mikesell P. 1993. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis 167:1239–1243. [PubMed][CrossRef]
114. Fritz DL, Jaax NK, Lawrence WB, Davis KJ, Pitt ML, Ezzell JW, Friedlander AM. 1995. Pathology of experimental inhalation anthrax in the rhesus monkey. Lab Invest 73:691–702. [PubMed]
115. Guidi-Rontani C. 2002. The alveolar macrophage: the Trojan horse of Bacillus anthracis. Trends Microbiol 10:405–409. [PubMed][CrossRef]
116. Guidi-Rontani C, Weber-Levy M, Labruyere E, Mock M. 1999. Germination of Bacillus anthracis spores within alveolar macrophages. Mol Microbiol 31:9–17. [PubMed][CrossRef]
117. Carr KA, Lybarger SR, Anderson EC, Janes BK, Hanna PC. 2010. The role of Bacillus anthracis germinant receptors in germination and virulence. Mol Microbiol 75:365–375. [PubMed][CrossRef]
118. McKevitt MT, Bryant KM, Shakir SM, Larabee JL, Blanke SR, Lovchik J, Lyons CR, Ballard JD. 2007. Effects of endogenous D-alanine synthesis and autoinhibition of Bacillus anthracis germination on in vitro and in vivo infections. Infect Immun 75:5726–5734. [PubMed][CrossRef]
119. Cote CK, Bozue J, Twenhafel N, Welkos SL. 2009. Effects of altering the germination potential of Bacillus anthracis spores by exogenous means in a mouse model. J Med Microbiol 58:816–825. [PubMed][CrossRef]
120. Fisher N, Shetron-Rama L, Herring-Palmer A, Heffernan B, Bergman N, Hanna P. 2006. The dltABCD operon of Bacillus anthracis sterne is required for virulence and resistance to peptide, enzymatic, and cellular mediators of innate immunity. J Bacteriol 188:1301–1309. [PubMed][CrossRef]
121. Cendrowski S, MacArthur W, Hanna P. 2004. Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence. Mol Microbiol 51:407–417. [PubMed][CrossRef]
122. Chung MC, Popova TG, Jorgensen SC, Dong L, Chandhoke V, Bailey CL, Popov SG. 2008. Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem 283:9531–9542. [PubMed][CrossRef]
123. Chung MC, Popova TG, Millis BA, Mukherjee DV, Zhou W, Liotta LA, Petricoin EF, Chandhoke V, Bailey C, Popov SG. 2006. Secreted neutral metalloproteases of Bacillus anthracis as candidate pathogenic factors. J Biol Chem 281:31408–31418. [PubMed][CrossRef]
124. Cowan GJ, Atkins HS, Johnson LK, Titball RW, Mitchell TJ. 2007. Immunisation with anthrolysin O or a genetic toxoid protects against challenge with the toxin but not against Bacillus anthracis. Vaccine 25:7197–7205. [PubMed][CrossRef]
125. Heffernan BJ, Thomason B, Herring-Palmer A, Shaughnessy L, McDonald R, Fisher N, Huffnagle GB, Hanna P. 2006. Bacillus anthracis phospholipases C facilitate macrophage-associated growth and contribute to virulence in a murine model of inhalation anthrax. Infect Immun 74:3756–3764. [PubMed][CrossRef]
126. Honsa ES, Fabian M, Cardenas AM, Olson JS, Maresso AW. 2011. The five near-iron transporter (NEAT) domain anthrax hemophore, IsdX2, scavenges heme from hemoglobin and transfers heme to the surface protein IsdC. J Biol Chem 286:33652–33660. [PubMed][CrossRef]
127. Honsa ES, Maresso AW. 2011. Mechanisms of iron import in anthrax. Biometals 24:533–545. [PubMed][CrossRef]
128. Mosser EM, Rest RF. 2006. The Bacillus anthracis cholesterol-dependent cytolysin, Anthrolysin O, kills human neutrophils, monocytes and macrophages. BMC Microbiol 6:56. doi:10.1186/1471-2180-6-56. [PubMed][CrossRef]
129. Mukherjee DV, Tonry JH, Kim KS, Ramarao N, Popova TG, Bailey C, Popov S, Chung MC. 2011. Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. PLoS One 6:e17921. doi:10.1371/journal.pone.0017921. [PubMed][CrossRef]
130. Shannon JG, Ross CL, Koehler TM, Rest RF. 2003. Characterization of anthrolysin O, the Bacillus anthracis cholesterol-dependent cytolysin. Infect Immun 71:3183–3189. [PubMed][CrossRef]
131. Shatalin K, Gusarov I, Avetissova E, Shatalina Y, McQuade LE, Lippard SJ, Nudler E. 2008. Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages. Proc Natl Acad Sci USA 105:1009–1013. [PubMed][CrossRef]
132. Bozue J, Moody KL, Cote CK, Stiles BG, Friedlander AM, Welkos SL, Hale ML. 2007. Bacillus anthracis spores of the bclA mutant exhibit increased adherence to epithelial cells, fibroblasts, and endothelial cells but not to macrophages. Infect Immun 75:4498–4505. [PubMed][CrossRef]
133. Brahmbhatt TN, Janes BK, Stibitz ES, Darnell SC, Sanz P, Rasmussen SB, O'Brien AD. 2007. Bacillus anthracis exosporium protein BclA affects spore germination, interaction with extracellular matrix proteins, and hydrophobicity. Infect Immun 75:5233–5239. [PubMed][CrossRef]
134. Oliva C, Turnbough CL, Jr, Kearney JF. 2009. CD14-Mac-1 interactions in Bacillus anthracis spore internalization by macrophages. Proc Natl Acad Sci USA 106:13957–13962. [PubMed][CrossRef]
135. Sylvestre P, Couture-Tosi E, Mock M. 2002. A collagen-like surface glycoprotein is a structural component of the Bacillus anthracis exosporium. Mol Microbiol 45:169–178. [PubMed][CrossRef]
136. Flick-Smith HC, Walker NJ, Gibson P, Bullifent H, Hayward S, Miller J, Titball RW, Williamson ED. 2002. A recombinant carboxy-terminal domain of the protective antigen of Bacillus anthracis protects mice against anthrax infection. Infect Immun 70:1653–1656. [PubMed][CrossRef]
137. Flick-Smith HC, Waters EL, Walker NJ, Miller J, Stagg AJ, Green M, Williamson ED. 2005. Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain. Microb Pathog 38:33–40. [PubMed][CrossRef]
138. Welkos SL, Friedlander AM. 1988. Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice. Microb Pathog 5:127–139. [PubMed][CrossRef]
139. Brahmbhatt TN, Darnell SC, Carvalho HM, Sanz P, Kang TJ, Bull RL, Rasmussen SB, Cross AS, O'Brien AD. 2007. Recombinant exosporium protein BclA of Bacillus anthracis is effective as a booster for mice primed with suboptimal amounts of protective antigen. Infect Immun 75:5240–5247. [PubMed][CrossRef]
140. Cybulski RJ, Jr, Sanz P, McDaniel D, Darnell S, Bull RL, O'Brien AD. 2008. Recombinant Bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigen. Vaccine 26:4927–4939. [PubMed][CrossRef]
141. Duc le H, Hong HA, Atkins HS, Flick-Smith HC, Durrani Z, Rijpkema S, Titball RW, Cutting SM. 2007. Immunization against anthrax using Bacillus subtilis spores expressing the anthrax protective antigen. Vaccine 25:346–355. [PubMed][CrossRef]
142. Galen JE, Zhao L, Chinchilla M, Wang JY, Pasetti MF, Green J, Levine MM. 2004. Adaptation of the endogenous Salmonella enterica serovar Typhi clyA-encoded hemolysin for antigen export enhances the immunogenicity of anthrax protective antigen domain 4 expressed by the attenuated live-vector vaccine strain CVD 908-htrA. Infect Immun 72:7096–7106. [PubMed][CrossRef]
143. Garmory HS, Titball RW, Griffin KF, Hahn U, Bohm R, Beyer W. 2003. Salmonella enterica serovar Typhimurium expressing a chromosomally integrated copy of the Bacillus anthracis protective antigen gene protects mice against an anthrax spore challenge. Infect Immun 71:3831–3836. [PubMed][CrossRef]
144. Lee JS, Groebner JL, Hadjipanayis AG, Negley DL, Schmaljohn AL, Welkos SL, Smith LA, Smith JF. 2006. Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice. Vaccine 24:6886–6892. [PubMed][CrossRef]
145. Lee JS, Hadjipanayis AG, Welkos SL. 2003. Venezuelan equine encephalitis virus-vectored vaccines protect mice against anthrax spore challenge. Infect Immun 71:1491–1496. [PubMed][CrossRef]
146. Stokes MG, Titball RW, Neeson BN, Galen JE, Walker NJ, Stagg AJ, Jenner DC, Thwaite JE, Nataro JP, Baillie LW, Atkins HS. 2007. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect Immun 75:1827–1834. [PubMed][CrossRef]
147. Tan Y, Hackett NR, Boyer JL, Crystal RG. 2003. Protective immunity evoked against anthrax lethal toxin after a single intramuscular administration of an adenovirus-based vaccine encoding humanized protective antigen. Hum Gene Ther 14:1673–1682. [PubMed][CrossRef]
148. Zeng M, Xu Q, Hesek ED, Pichichero ME. 2006. N-fragment of edema factor as a candidate antigen for immunization against anthrax. Vaccine 24:662–670. [PubMed][CrossRef]
149. Vergis JM, Cote CK, Bozue J, Alem F, Ventura CL, Welkos SL, O'Brien AD. 2013. Immunization of mice with formalin-inactivated spores from avirulent Bacillus cereus strains provides significant protection from challenge with Bacillus anthracis Ames. Clin Vacc Immunol 20:56–65. [PubMed][CrossRef]
150. Basu S, Kang T, Whitford M, Meldorf M, Lowry I, Cross A. 2009. Mechanisms of an anti-PA antibody (Valortim) that mediate protection against B. anthracis infection, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Santa Fe, NM, 30 August to 3 September, 2009.
151. Basu S, Kang TJ, Langermann S, Riddle V, Lowy I, Cross AS. 2007. A monoclonal antibody that neutralizes lethal toxin mediates the killing of B. anthracis by murine macrophages, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Oslo, Norway, 17 to 21 June 2007.
152. Mett V, Chichester JA, Stewart ML, Musiychuk K, Bi H, Reifsnyder CJ, Hull AK, Albrecht MT, Goldman S, Baillie LW, Yusibov V. 2011. A non-glycosylated, plant-produced human monoclonal antibody against anthrax protective antigen protects mice and non-human primates from B. anthracis spore challenge. Hum Vaccin 7(Suppl):183–190. [PubMed][CrossRef]
153. Cote CK, Rossi CA, Kang AS, Morrow PR, Lee JS, Welkos SL. 2005. The detection of protective antigen (PA) associated with spores of Bacillus anthracis and the effects of anti-PA antibodies on spore germination and macrophage interactions. Microb Pathog 38:209–225. [PubMed][CrossRef]
154. Welkos S, Friedlander A, Weeks S, Little S, Mendelson I. 2002. In-vitro characterisation of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody. J Med Microbiol 51:821–831. [PubMed]
155. Welkos S, Little S, Friedlander A, Fritz D, Fellows P. 2001. The role of antibodies to Bacillus anthracis and anthrax toxin components in inhibiting the early stages of infection by anthrax spores. Microbiology 147:1677–1685. [PubMed]
156. Vuyisich M, Gnanakaran S, Lovchik JA, Lyons CR, Gupta G. 2008. A dual-purpose protein ligand for effective therapy and sensitive diagnosis of anthrax. Protein J 27:292–302. [PubMed][CrossRef]
157. Brossier F, Weber-Levy M, Mock M, Sirard JC. 2000. Role of toxin functional domains in anthrax pathogenesis. Infect Immun 68:1781–1786. [PubMed][CrossRef]
158. Kalns J, Morris J, Eggers J, Kiel J. 2002. Delayed treatment with doxycycline has limited effect on anthrax infection in BLK57/B6 mice. Biochem Biophys Res Commun 297:506–509. [PubMed][CrossRef]
159. Pezard C, Berche P, Mock M. 1991. Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun 59:3472–3477. [PubMed]
160. Pezard C, Duflot E, Mock M. 1993. Construction of Bacillus anthracis mutant strains producing a single toxin component. J Gen Microbiol 139(Pt 10):2459–2463. [PubMed][CrossRef]
161. Pezard C, Sirard JC, Mock M. 1996. Protective immunity induced by Bacillus anthracis toxin mutant strains. Adv Exp Med Biol 397:69–72. [PubMed][CrossRef]
162. Pezard C, Weber M, Sirard JC, Berche P, Mock M. 1995. Protective immunity induced by Bacillus anthracis toxin-deficient strains. Infect Immun 63:1369–1372. [PubMed]
163. Russell BH, Liu Q, Jenkins SA, Tuvim MJ, Xu Y. 2008. In vivo demonstration and quantification of intracellular Bacillus anthracis in lung epithelial cells. Infect Immun 76:3975–3983. [PubMed][CrossRef]
164. Zaucha GM, Pitt LM, Estep J, Ivins BE, Friedlander AM. 1998. The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation. Arch Pathol Lab Med 122:982–992. [PubMed]
165. Kalns J, Scruggs J, Millenbaugh N, Vivekananda J, Shealy D, Eggers J, Kiel J. 2002. TNF receptor 1, IL-1 receptor, and iNOS genetic knockout mice are not protected from anthrax infection. Biochem Biophys Res Commun 292:41–44. [PubMed][CrossRef]
166. Hahn BL, Sharma S, Sohnle PG. 2005. Analysis of epidermal entry in experimental cutaneous Bacillus anthracis infections in mice. J Lab Clin Med 146:95–102. [PubMed][CrossRef]
167. Hahn BL, Bischof TS, Sohnle PG. 2008. Superficial exudates of neutrophils prevent invasion of Bacillus anthracis bacilli into abraded skin of resistant mice. Int J Exp Pathol 89:180–187. [PubMed][CrossRef]
168. van Sorge NM, Ebrahimi CM, McGillivray SM, Quach D, Sabet M, Guiney DG, Doran KS. 2008. Anthrax toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitis. PLoS One 3:e2964. doi:10.1371/journal.pone.0002964. [PubMed][CrossRef]
169. Ebrahimi CM, Sheen TR, Renken CW, Gottlieb RA, Doran KS. 2011. Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infect Immun 79:2510–2518. [PubMed][CrossRef]
170. Friedlander AM. 1986. Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J Biol Chem 261:7123–7126. [PubMed]
171. Friedlander AM, Bhatnagar R, Leppla SH, Johnson L, Singh Y. 1993. Characterization of macrophage sensitivity and resistance to anthrax lethal toxin. Infect Immun 61:245–252. [PubMed]
172. Guidi-Rontani C, Levy M, Ohayon H, Mock M. 2001. Fate of germinated Bacillus anthracis spores in primary murine macrophages. Mol Microbiol 42:931–938. [PubMed][CrossRef]
173. Guidi-Rontani C, Pereira Y, Ruffie S, Sirard JC, Weber-Levy M, Mock M. 1999. Identification and characterization of a germination operon on the virulence plasmid pXO1 of Bacillus anthracis. Mol Microbiol 33:407–414. [PubMed][CrossRef]
174. Brittingham KC, Ruthel G, Panchal RG, Fuller CL, Ribot WJ, Hoover TA, Young HA, Anderson AO, Bavari S. 2005. Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis. J Immunol 174:5545–5552. [PubMed][CrossRef]
175. Cleret A, Quesnel-Hellmann A, Mathieu J, Vidal D, Tournier JN. 2006. Resident CD11c+ lung cells are impaired by anthrax toxins after spore infection. J Infect Dis 194:86–94. [PubMed][CrossRef]
176. Tournier JN, Quesnel-Hellmann A, Mathieu J, Montecucco C, Tang WJ, Mock M, Vidal DR, Goossens PL. 2005. Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells. J Immunol 174:4934–4941. [PubMed][CrossRef]
177. Hsu LC, Ali SR, McGillivray S, Tseng PH, Mariathasan S, Humke EW, Eckmann L, Powell JJ, Nizet V, Dixit VM, Karin M. 2008. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci USA 105:7803–7808. [PubMed][CrossRef]
178. Duesbery NS, Webb CP, Leppla SH, Gordon VM, Klimpel KR, Copeland TD, Ahn NG, Oskarsson MK, Fukasawa K, Paull KD, Vande Woude GF. 1998. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280:734–737. [PubMed][CrossRef]
179. Moayeri M, Leppla SH. 2009. Cellular and systemic effects of anthrax lethal toxin and edema toxin. Mol Aspects Med 30:439–455. [PubMed][CrossRef]
180. Park JM, Greten FR, Li ZW, Karin M. 2002. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297:2048–2051. [PubMed][CrossRef]
181. Pellizzari R, Guidi-Rontani C, Vitale G, Mock M, Montecucco C. 1999. Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha. FEBS Lett 462:199–204. [PubMed][CrossRef]
182. Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C. 1998. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun 248:706–711. [PubMed][CrossRef]
183. Leppla SH. 1982. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci USA 79:3162–3166. [PubMed][CrossRef]
184. Roberts JE, Watters JW, Ballard JD, Dietrich WF. 1998. Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11. Mol Microbiol 29:581–591. [PubMed][CrossRef]
185. Boyden ED, Dietrich WF. 2006. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38:240–244. [PubMed][CrossRef]
186. Martinon F. 2007. Orchestration of pathogen recognition by inflammasome diversity: variations on a common theme. Eur J Immunol 37:3003–3006. [PubMed][CrossRef]
187. Tschopp J. 1989. NALPs: resistance to Sterne strain of Bacillus anthracis: phagocytic cell response of resistant and susceptible mice. Microb Pathog 7:15–35. [PubMed][CrossRef]
188. Hanna PC, Acosta D, Collier RJ. 1993. On the role of macrophages in anthrax. Proc Natl Acad Sci USA 90:10198–10201. [PubMed][CrossRef]
189. Moayeri M, Martinez NW, Wiggins J, Young HA, Leppla SH. 2004. Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. Infect Immun 72:4439–4447. [PubMed][CrossRef]
190. Terra JK, France B, Cote CK, Jenkins A, Bozue J, Welkos SL, Lusis AJ, Davis R, LeVine SM, Bradley KA. 2011. Identification of a novel quantitative trait locus controlling inflammatory response to anthrax lethal toxin and resistance to Bacillus anthracis. PLoS Pathog 7(12):e1002469. [PubMed][CrossRef]
191. Banks DJ, Barnajian M, Maldonado-Arocho FJ, Sanchez AM, Bradley KA. 2005. Anthrax toxin receptor 2 mediates Bacillus anthracis killing of macrophages following spore challenge. Cell Microbiol 7:1173–1185. [PubMed][CrossRef]
192. Liu S, Crown D, Miller-Randolph S, Moayeri M, Wang H, Hu H, Morley T, Leppla SH. 2009. Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo. Proc Natl Acad Sci USA 106:12424–12429. [PubMed][CrossRef]
193. Moayeri M, Haines D, Young HA, Leppla SH. 2003. Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. J Clin Invest 112:670–682. [PubMed][CrossRef]
194. Brossier F, Levy M, Mock M. 2002. Anthrax spores make an essential contribution to vaccine efficacy. Infect Immun 70:661–664. [PubMed]
195. Chand HS, Drysdale M, Lovchik J, Koehler TM, Lipscomb MF, Lyons CR. 2009. Discriminating virulence mechanisms among Bacillus anthracis strains by using a murine subcutaneous infection model. Infect Immun 77:429–435. [PubMed][CrossRef]
196. Gauthier YP, Tournier JN, Paucod JC, Corre JP, Mock M, Goossens PL, Vidal DR. 2009. Efficacy of a vaccine based on protective antigen and killed spores against experimental inhalational anthrax. Infect Immun 77:1197–1207. [PubMed][CrossRef]
197. Little SF, Knudson GB. 1986. Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig. Infect Immun 52:509–512. [PubMed]
198. Moen ST, Yeager LA, Lawrence WS, Ponce C, Galindo CL, Garner HR, Baze WB, Suarez G, Peterson JW, Chopra AK. 2008. Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores. Microb Pathog 44:293–310. [PubMed][CrossRef]
199. Vasconcelos D, Barnewall R, Babin M, Hunt R, Estep J, Nielsen C, Carnes R, Carney J. 2003. Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis). Lab Invest 83:1201–1209. [PubMed][CrossRef]
200. Hahn UK, Boehm R, Beyer W. 2006. DNA vaccination against anthrax in mice-combination of anti-spore and anti-toxin components. Vaccine 24:4569–4571. [PubMed][CrossRef]
201. Kozel TR, Murphy WJ, Brandt S, Blazar BR, Lovchik JA, Thorkildson P, Percival A, Lyons CR. 2004. mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia. Proc Natl Acad Sci USA 101:5042–5047. [PubMed][CrossRef]
202. Barr JR, Boyer AE, Hoffmaster AR, Quinn CP, Gallegos-Candela M, Lins RC, Shadomy SV, Lehman M, Pesik N, Jahangir H, Chakraborty A, Ramsay CN, Smith TL, Pirkle JL. 2011. Detection and quantification of anthrax toxins by mass spectrometry-application to clinical anthrax, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruges, Belgium, 7 to 11 August 2011.
203. Boyer AE, Lins RC, Gallegos-Candella M, Kuklenyik Z, Quinn CP, Hoffmaster A, Marston CK, Beesley CA, Barr JR. 2011. Kinetics of anthrax toxins, lethal factor, edmea factor, and lethal toxin during inhalational anthrax in rhesus macaques, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruges, Belgium, 7 to 11 August 2011.
204. Meister G, Blosser E, Herr-Calomeni P, Padgett N, Mott J. 2007. Development of an inhalational Bacillus anthracis exposure therapeutic model in New Zealand White rabbits, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Oslo, Norway, 17 to 21 June 2007.
205. Bergman NH, Passalacqua KD, Gaspard R, Shetron-Rama LM, Quackenbush J, Hanna PC. 2005. Murine macrophage transcriptional responses to Bacillus anthracis infection and intoxication. Infect Immun 73:1069–1080. [PubMed][CrossRef]
206. Bradley KA, LeVine SM. 2010. Anthrax toxin delivers a one-two punch. Cell Host Microbe 8:394–395. [PubMed][CrossRef]
207. Cote CK, Dimezzo TL, Banks DJ, France B, Bradley KA, Welkos SL. 2008. Early interactions between fully virulent Bacillus anthracis and macrophages that influence the balance between spore clearance and development of a lethal infection. Microbes Infect. 10:613–619. [PubMed][CrossRef]
208. Giorno R, Bozue J, Cote C, Wenzel T, Moody KS, Mallozzi M, Ryan M, Wang R, Zielke R, Maddock JR, Friedlander A, Welkos S, Driks A. 2007. Morphogenesis of the Bacillus anthracis spore. J Bacteriol 189:691–705. [PubMed][CrossRef]
209. Giorno R, Mallozzi M, Bozue J, Moody KS, Slack A, Qiu D, Wang R, Friedlander A, Welkos S, Driks A. 2009. Localization and assembly of proteins comprising the outer structures of the Bacillus anthracis spore. Microbiology 155:1133–1145. [PubMed][CrossRef]
210. Mallozzi M, Bozue J, Giorno R, Moody KS, Slack A, Cote C, Qiu D, Wang R, McKenney P, Lai EM, Maddock JR, Friedlander A, Welkos S, Eichenberger P, Driks A. 2008. Characterization of a Bacillus anthracis spore coat-surface protein that influences coat-surface morphology. FEMS Microbiol Lett 289:110–117. [PubMed][CrossRef]
211. Severson KM, Mallozzi M, Bozue J, Welkos SL, Cote CK, Knight KL, Driks A. 2009. Roles of the Bacillus anthracis spore protein ExsK in exosporium maturation and germination. J Bacteriol 191:7587–7596. [PubMed][CrossRef]
212. Bielinska AU, Janczak KW, Landers JJ, Makidon P, Sower LE, Peterson JW, Baker JR, Jr. 2007. Mucosal immunization with a novel nanoemulsion-based recombinant anthrax protective antigen vaccine protects against Bacillus anthracis spore challenge. Infect Immun 75:4020–4029. [PubMed][CrossRef]
213. Boyaka PN, Tafaro A, Fischer R, Leppla SH, Fujihashi K, McGhee JR. 2003. Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen. J Immunol 170:5636–5643. [PubMed][CrossRef]
214. Shivachandra SB, Li Q, Peachman KK, Matyas GR, Leppla SH, Alving CR, Rao M, Rao VB. 2007. Multicomponent anthrax toxin display and delivery using bacteriophage T4. Vaccine 25:1225–1235. [PubMed][CrossRef]
215. Williamson ED, Beedham RJ, Bennett AM, Perkins SD, Miller J, Baillie LW. 1999. Presentation of protective antigen to the mouse immune system: immune sequelae. J Appl Microbiol 87:315–317. [PubMed][CrossRef]
216. Gaur R, Gupta PK, Banerjea AC, Singh Y. 2002. Effect of nasal immunization with protective antigen of Bacillus anthracis on protective immune response against anthrax toxin. Vaccine 20:2836–2839. [PubMed][CrossRef]
217. Gu M, Hine PM, James Jackson W, Giri L, Nabors GS. 2007. Increased potency of BioThrax anthrax vaccine with the addition of the C-class CpG oligonucleotide adjuvant CPG 10109. Vaccine 25:526–534. [PubMed][CrossRef]
218. Matyas GR, Friedlander AM, Glenn GM, Little S, Yu J, Alving CR. 2004. Needle-free skin patch vaccination method for anthrax. Infect Immun 72:1181–1183. [PubMed][CrossRef]
219. Mikszta JA, Sullivan VJ, Dean C, Waterston AM, Alarcon JB, Dekker JP, 3rd, Brittingham JM, Huang J, Hwang CR, Ferriter M, Jiang G, Mar K, Saikh KU, Stiles BG, Roy CJ, Ulrich RG, Harvey NG. 2005. Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms. J Infect Dis 191:278–288. [PubMed][CrossRef]
220. Peachman KK, Rao M, Alving CR, Burge R, Leppla SH, Rao VB, Matyas GR. 2006. Correlation between lethal toxin-neutralizing antibody titers and protection from intranasal challenge with Bacillus anthracis Ames strain spores in mice after transcutaneous immunization with recombinant anthrax protective antigen. Infect Immun 74:794–797. [PubMed][CrossRef]
221. Chabot DJ, Scorpio A, Tobery SA, Little SF, Norris SL, Friedlander AM. 2004. Anthrax capsule vaccine protects against experimental infection. Vaccine 23:43–47. [PubMed][CrossRef]
222. Iacono-Connors LC, Welkos SL, Ivins BE, Dalrymple JM. 1991. Protection against anthrax with recombinant virus-expressed protective antigen in experimental animals. Infect Immun 59:1961–1965. [PubMed]
223. Ivins BE, Welkos SL, Knudson GB, Little SF. 1990. Immunization against anthrax with aromatic compound-dependent (Aro-) mutants of Bacillus anthracis and with recombinant strains of Bacillus subtilis that produce anthrax protective antigen. Infect Immun 58:303–308. [PubMed]
224. Welkos SL, Cote CK, Rea KM, Gibbs PH. 2004. A microtiter fluorometric assay to detect the germination of Bacillus anthracis spores and the germination inhibitory effects of antibodies. J Microbiol Methods 56:253–265. [PubMed][CrossRef]
225. Piris Gimenez A, Wu Y-Z, Paya M, Delclaux C, Touqui L, Goosens PL. 2004. High bactericidal efficiency of type IIA phospholipase A2 against Bacillus anthracis and inhibition of its secretion by the lethal toxin. J Immunol 173:521–530. [PubMed][CrossRef]
226. Piris-Gimenez A, Paya M, Lambeau G, Chignard M, Mock M, Touqui L, Goossens PL. 2005. In vivo protective role of human group IIa phospholipase A2 against experimental anthrax. J Immunol 175:6786–6791. [PubMed][CrossRef]
227. Peterson JW, Moen ST, Healy D, Pawlik JE, Taormina J, Hardcastle J, Thomas JM, Lawrence WS, Ponce C, Chatuev BM, Gnade BT, Foltz SM, Agar SL, Sha J, Klimpel GR, Kirtley ML, Eaves-Pyles T, Chopra AK. 2010. Protection afforded by fluoroquinolones in animal models of respiratory infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis. Open Microbiol J 4:34–46. [PubMed][CrossRef]
228. Steward J, Lever MS, Simpson AJ, Sefton AM, Brooks TJ. 2004. Post-exposure prophylaxis of systemic anthrax in mice and treatment with fluoroquinolones. J Antimicrob Chemother 54:95–99. [PubMed][CrossRef]
229. Louie A, Heine HS, Kim K, Brown DL, VanScoy B, Liu W, Kinzig-Schippers M, Sorgel F, Drusano GL. 2008. Use of an in vitro pharmacodynamic model to derive a linezolid regimen that optimizes bacterial kill and prevents emergence of resistance in Bacillus anthracis. Antimicrob Agents Chemother 52:2486–2496. [PubMed][CrossRef]
230. Peterson JW, Comer JE, Noffsinger DM, Wenglikowski A, Walberg KG, Chatuev BM, Chopra AK, Stanberry LR, Kang AS, Scholz WW, Sircar J. 2006. Human monoclonal anti-protective antigen antibody completely protects rabbits and is synergistic with ciprofloxacin in protecting mice and guinea pigs against inhalation anthrax. Infect Immun 74:1016–1024. [PubMed][CrossRef]
231. Chen Z, Schneerson R, Lovchik J, Lyons CR, Zhao H, Dai Z, Kubler-Kielb J, Leppla SH, Purcell RH. 2011. Pre- and postexposure protection against virulent anthrax infection in mice by humanized monoclonal antibodies to Bacillus anthracis capsule. Proc Natl Acad Sci USA 108:739–744. [PubMed][CrossRef]
232. Drysdale M, Heninger S, Hutt J, Chen Y, Lyons CR, Koehler TM. 2005. Capsule synthesis by Bacillus anthracis is required for dissemination in murine inhalation anthrax. EMBO J 24:221–227. [PubMed][CrossRef]
233. Ivins BE, Welkos SL. 1988. Recent advances in the development of an improved, human anthrax vaccine. Eur J Epidemiol 4:12–19. [PubMed][CrossRef]
234. Garufi G, Wang Y, Oh SY, Maier H, Schneewind O, Missiakas D. 2012. Sortase-conjugation generates a capsule vaccine that protects guinea pigs against Bacillus anthracis. Vaccine 30:3435-3444. [PubMed][CrossRef]
235. Cote C, Kaatz L, Reinhardt J, Bozue J, Tobery S, Bassett A, Sanz P, Darnell S, Alem F, O’Brien A, Welkos S. 2012. Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxemia. J Med Microbiol 61:1393-1400. [PubMed][CrossRef]
236. Glomski IJ, Corre JP, Mock M, Goossens PL. 2007. Cutting Edge: IFN-gamma-producing CD4 T lymphocytes mediate spore-induced immunity to capsulated Bacillus anthracis. J Immunol 178:2646–2650. [PubMed][CrossRef]
237. Scorpio A, Tobery SA, Ribot WJ, Friedlander AM. 2008. Treatment of experimental anthrax with recombinant capsule depolymerase. Antimicrob Agents Chemother 52:1014–1020. [PubMed][CrossRef]
238. Gill DM. 1982. Bacterial toxins: a table of lethal amounts. Microbiol Rev 46:86–94. [PubMed]
239. Jones WI, Jr, Klein F, Walker JS, Mahlandt BG, Dobbs JP, Lincoln RE. 1967. In vivo growth and distribution of anthrax bacilli in resistant, susceptible, and immunized hosts. J Bacteriol 94:600–608. [PubMed]
240. Day J, Friedman A, Schlesinger LS. 2011. Modeling the host response to inhalation anthrax. J Theor Biol 276:199–208. [PubMed][CrossRef]
241. Popov S. 2008. New candidate anthrax pathogenic factors, p 25–35. In Georgiev V, Western KA, McGowan JJ (ed), National Institute of Allergy and Infectious Diseases, NIH, vol I. Frontiers in Research. Humana Press, Inc., Totowa, NJ.
242. Moayeri M, Leppla SH. 2004. The roles of anthrax toxin in pathogenesis. Curr Opin Microbiol 7:19–24. [PubMed][CrossRef]
243. Moayeri M, Crown D, Dorward DW, Gardner D, Ward JM, Li Y, Cui X, Eichacker P, Leppla SH. 2009. The heart is an early target of anthrax lethal toxin in mice: a protective role for neuronal nitric oxide synthase (nNOS). PLoS Pathog 5:e1000456. doi:10.1371/journal.ppat.1000456. [PubMed][CrossRef]
244. Duverger A, Jackson RJ, van Ginkel FW, Fischer R, Tafaro A, Leppla SH, Fujihashi K, Kiyono H, McGhee JR, Boyaka PN. 2006. Bacillus anthracis edema toxin acts as an adjuvant for mucosal immune responses to nasally administered vaccine antigens. J Immunol 176:1776–1783. [PubMed][CrossRef]
245. Firoved AM, Miller GF, Moayeri M, Kakkar R, Shen Y, Wiggins JF, McNally EM, Tang WJ, Leppla SH. 2005. Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice. Am J Pathol 167:1309–1320. [PubMed][CrossRef]
246. Crowe SR, Garman L, Engler RJ, Farris AD, Ballard JD, Harley JB, James JA. 2011. Anthrax vaccination induced anti-lethal factor IgG: fine specificity and neutralizing capacity. Vaccine 29:3670–3678. [PubMed][CrossRef]
247. Aulinger BA, Roehrl MH, Mekalanos JJ, Collier RJ, Wang JY. 2005. Combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccines. Infect Immun 73:3408–3414. [PubMed][CrossRef]
248. Chen Z, Moayeri M, Zhao H, Crown D, Leppla SH, Purcell RH. 2009. Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding. Proc Natl Acad Sci USA 106:13487–13492. [PubMed][CrossRef]
249. Kulshreshtha P, Bhatnagar R. 2011. Inhibition of anthrax toxins with a bispecific monoclonal antibody that cross reacts with edema factor as well as lethal factor of Bacillus anthracis. Mol Immunol 48:1958–1965. [PubMed][CrossRef]
250. vor dem Esche U, Huber M, Zgaga-Griesz A, Grunow R, Beyer W, Hahn U, Bessler WG. 2011. Passive vaccination with a human monoclonal antibody: generation of antibodies and studies for efficacy in Bacillus anthracis infections. Immunobiology 216:847–853. [PubMed][CrossRef]
251. Cromartie WJ, Bloom WL, Watson DS. 1947. Studies on infection with Bacillus anthracis. J Infect Dis 80:1–52. [CrossRef]
252. Cromartie WJ, Bloom WL, Watson DW. 1947. Studies on infection with Bacillus anthracis. II. A histopathological study of skin lesions produced by B. anthracis in susceptible and resistant animal species. J Infect Dis 80:1–13. [PubMed][CrossRef]
253. Cromartie WJ, Watson DW, Bloom WL, Heckly RJ. 1947. Studies on infection with Bacillus anthracis. II. The immunological and tissue damaging properties of extracts prepared from lesions of B. anthracis infections. J Infect Dis 80:14–27. [PubMed][CrossRef]
254. Smith H, Keppie J, Stanley JL. 1954. Observations on the cause of death in experimental anthrax. Lancet 267:474–476. [PubMed][CrossRef]
255. Smith H, Keppie J, Stanley JL, Harris-Smith PW. 1955. The chemical basis of the virulence of Bacillus anthracis. IV. Secondary shock as the major factor in death of guinea-pigs from anthrax. Br J Exp Pathol 36:323–335. [PubMed]
256. Ward MK, McGann VG, Hogge AL, Jr, Huff ML, Kanode RG, Jr, Roberts EO. 1965. Studies on anthrax infections in immunized guinea pigs. J Infect Dis 115:59–67. [PubMed][CrossRef]
257. Walker JS, Klein F, Lincoln RE, Fernelius AL. 1967. Temperature response in animals infected with Bacillus anthracis. J Bacteriol 94:552–556. [PubMed]
258. Lincoln RE, Rhian MM, Klein F, Fernelius A. 1961. Pathogenesis as Related to Physiological State of Anthrax Spore and Cell. Burgess Publishing Company, Minneapolis, MN.
259. Jenkins A, Cote C, Twenhafel N, Merkel T, Bozue J, Welkos S. 2011. Role of purine biosynthesis in Bacillus anthracis pathogenesis and virulence. Infect Immun 79:153–166. [PubMed][CrossRef]
260. Coker PR, Smith KL, Fellows PF, Rybachuck G, Kousoulas KG, Hugh-Jones ME. 2003. Bacillus anthracis virulence in guinea pigs vaccinated with anthrax vaccine adsorbed is linked to plasmid quantities and clonality. J Clin Microbiol 41:1212–1218. [PubMed][CrossRef]
261. Chitlaru T, Zaide G, Gat O, Ariel N, Zvi A, Grosfeld H, Cohen O, Shafferman A. 2011. Novel essential virulence determinants of Bacillus anthracis identified by various complementary high throughput analyses, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruges, Belgium, 7 to 11 August 2011.
262. Bozue JA, Parthasarathy N, Phillips LR, Cote CK, Fellows PF, Mendelson I, Shafferman A, Friedlander AM. 2005. Construction of a rhamnose mutation in Bacillus anthracis affects adherence to macrophages but not virulence in guinea pigs. Microb Pathog 38:1–12. [PubMed][CrossRef]
263. Chitlaru T, Gat O, Grosfeld H, Inbar I, Gozlan Y, Shafferman A. 2007. Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome. Infect Immun 75:2841–2852. [PubMed][CrossRef]
264. Cote CK, Bozue J, Moody KL, DiMezzo TL, Chapman CE, Welkos SL. 2008. Analysis of a novel spore antigen in Bacillus anthracis that contributes to spore opsonization. Microbiology 154:619–632. [PubMed][CrossRef]
265. Scorpio A, Chabot DJ, Day WA, Hoover TA, Friedlander AM. Capsule depolymerase overexpression reduces Bacillus anthracis virulence. Microbiology 156:1459–1467. [PubMed][CrossRef]
266. Ivins BE, Fellows PF, Nelson GO. 1994. Efficacy of a standard human anthrax vaccine against Bacillus anthracis spore challenge in guinea-pigs. Vaccine 12:872–874. [CrossRef]
267. Turnbull PC, Broster MG, Carman JA, Manchee RJ, Melling J. 1986. Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity. Infect Immun 52:356–363. [PubMed]
268. Kobiler D, Gozes Y, Rosenberg H, Marcus D, Reuveny S, Altboum Z. 2002. Efficiency of protection of guinea pigs against infection with Bacillus anthracis spores by passive immunization. Infect Immun 70:544–560. [PubMed][CrossRef]
269. Little SF, Ivins BE, Fellows PF, Friedlander AM. 1997. Passive protection by polyclonal antibodies against Bacillus anthracis infection in guinea pigs. Infect Immun 65:5171–5175. [PubMed]
270. Reuveny S, White MD, Adar YY, Kafri Y, Altboum Z, Gozes Y, Kobiler D, Shafferman A, Velan B. 2001. Search for correlates of protective immunity conferred by anthrax vaccine. Infect Immun 69:2888–2893. [PubMed][CrossRef]
271. Lee DY, Chun JH, Ha HJ, Park J, Kim BS, Oh HB, Rhie GE. 2009. Poly-gamma-d-glutamic acid and protective antigen conjugate vaccines induce functional antibodies against the protective antigen and capsule of Bacillus anthracis in guinea-pigs and rabbits. FEMS Immunol Med Microbiol 57:165–172. [PubMed][CrossRef]
272. Skoble J, Beaber JW, Gao Y, Lovchik JA, Sower LE, Liu W, Luckett W, Peterson JW, Calendar R, Portnoy DA, Lyons CR, Dubensky TW, Jr. 2009. Killed but metabolically active Bacillus anthracis vaccines induce broad and protective immunity against anthrax. Infect Immun 77:1649–1663. [PubMed][CrossRef]
273. Savransky V, Austin J, Tordoff K, Sanford D, Lemiale L, Park S, Nabors GS, Ionin B, Skiadopoulos MH. 2011. Protective efficacy of a novel anthrax vaccine against inhalational anthrax in guinea pigs is associated with induction of robust immune response, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruge, Belgium, 7 to 11 August 2011.
274. Twenhafel NA. 2010. Pathology of inhalational anthrax animal models. Vet Pathol 47:819–830. [PubMed][CrossRef]
275. Comer JE, Noffsinger DM, McHenry DJ, Weisbaum DM, Chatuev BM, Chopra AK, Peterson JW. 2006. Evaluation of the protective effects of quinacrine against Bacillus anthracis Ames. J Toxicol Environ Health A 69:1083–1095. [PubMed][CrossRef]
276. Lawrence WS, Hardcastle JM, Brining DL, Weaver LE, Ponce C, Whorton EB, Peterson JW. 2009. The physiologic responses of Dutch belted rabbits infected with inhalational anthrax. Comp Med 59:257–265. [PubMed]
277. Weiss S, Kobiler D, Levy H, Marcus H, Pass A, Rothschild N, Altboum Z. 2006. Immunological correlates for protection against intranasal challenge of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits. Infect Immun 74:394–398. [PubMed][CrossRef]
278. Palmer JR, Albrecht M, Groen H, Elberson M, Fonseca M, Barnwell R, Pesce J, Mateczun A, Kean-Myers A. 2011. Protective efficacy of candidate anthrax vaccines and medical countermeasures against an aerosol challenge with the novel Bacillus cereus G9241 strain, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruge, Belgium, 7 to 11 August 2011.
279. Burrows TW, Gillett WA. 1971. Host specificity of Brazilian strains of Pasteurella pestis. Nature 229:51–52. [PubMed][CrossRef]
280. Meyer KF, Smith G, Foster L, Brookman M, Sung M. 1974. Live, attenuated Yersinia pestis vaccine: virulent in nonhuman primates, harmless to guinea pigs. J Infect Dis 129(Suppl):S85–S12. [PubMed][CrossRef]
281. Oyston PC, Russell P, Williamson ED, Titball RW. 1996. An aroA mutant of Yersinia pestis is attenuated in guinea-pigs, but virulent in mice. Microbiology 142(Pt 7):1847–1853. [PubMed][CrossRef]
282. Levy H, Weiss S, Altboum Z, Schlomovitz J, Rothschild N, Blachinsky E, Kobiler D. 2011. Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits. Microb Pathog 51:345–351. [PubMed][CrossRef]
283. Yee SB, Hatkin JM, Dyer DN, Orr SA, Pitt ML. 2010. Aerosolized Bacillus anthracis infection in New Zealand white rabbits: natural history and intravenous levofloxacin treatment. Comp Med 60:461–468. [PubMed]
284. Wright GG, Hedberg MA, Feinberg RJ. 1951. Studies on immunity in anthrax. II. In vitro elaboration of protective antigen by non-proteolytic mutants of Bacillus anthracis. J Exp Med 93:523–527. [PubMed][CrossRef]
285. Fasanella A, Scasciamacchia S, Garofolo G. 2009. The behaviour of virulent Bacillus anthracis strain AO843 in rabbits. Vet Microbiol 133:208–209. [PubMed][CrossRef]
286. Yee SB, Dyer DN, Pitt MLM. 2011. Bacterial lipopolysaccharide-induced resistance to inhalational anthracis infection in New Zealand white rabbits, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruges, Belgium, 7 to 11 August 2011.
287. Lawrence WS, Marshall JR, Zavala DL, Weaver LE, Baze WB, Moen ST, Whorton EB, Gourley RL, Peterson JW. 2011. Hemodynamic effects of anthrax toxins in the rabbit model and the cardiac pathology induced by lethal toxin. Toxins 3:721–736. [PubMed][CrossRef]
288. Nordberg BK, Schmiterlow CG, Hansen HJ. 1961. Pathophysiological investigations into the terminal course of experimental anthrax in the rabbit. Acta Pathol Microbiol Scand 53:295–318. [PubMed][CrossRef]
289. Kobiler D, Weiss S, Levy H, Fisher M, Mechaly A, Pass A, Altboum Z. 2006. Protective antigen as a correlative marker for anthrax in animal models. Infect Immun 74:5871–5876. [PubMed][CrossRef]
290. Sela-Abramovich S, Chitlaru T, Gat O, Grosfeld H, Cohen O, Shafferman A. 2009. Novel and unique diagnostic biomarkers for Bacillus anthracis infection. Appl Environ Microbiol 75:6157–6167. [PubMed][CrossRef]
291. Wilson MK, Vergis JM, Alem F, Palmer JR, Keane-Myers AM, Brahmbhatt TN, Ventura CL, O'Brien AD. 2011. Bacillus cereus G9241 makes anthrax toxin and capsule like highly virulent B. anthracis Ames but behaves like attenuated toxigenic nonencapsulated B. anthracis Sterne in rabbits and mice. Infect Immun 79:3012–3019. [PubMed][CrossRef]
292. Hoffmaster AR, Ravel J, Rasko DA, Chapman GD, Chute JD, Chung KM, De BK, Sacchi CT, Fitzgerald C, Mauer LW, Maiden MCJ, Priest FG, Barker M, Jiang L, Cer RZ, Rilstone J, Peterson SN, Weyant RS, Galloway DR, Read TD, Popovic T, Fraser CM. 2004. Identification of anthrax toxin genes in Bacillus cereus associated with an illness resembling inhalation anthrax. Proc Natl Acad Sci USA 101:8449–8454. [PubMed][CrossRef]
293. Little SF, Ivins BE, Webster WM, Fellows PF, Pitt ML, Norris SL, Andrews GP. 2006. Duration of protection of rabbits after vaccination with Bacillus anthracis recombinant protective antigen vaccine. Vaccine 24:2530–2536. [PubMed][CrossRef]
294. Little SF, Ivins BE, Webster WM, Norris SL, Andrews GP. 2007. Effect of aluminum hydroxide adjuvant and formaldehyde in the formulation of rPA anthrax vaccine. Vaccine 25:2771–2777. [PubMed][CrossRef]
295. Ribot WJ, Powell BS, Ivins BE, Little SF, Johnson WM, Hoover TA, Norris SL, Adamovicz JJ, Friedlander AM, Andrews GP. 2006. Comparative vaccine efficacy of different isoforms of recombinant protective antigen against Bacillus anthracis spore challenge in rabbits. Vaccine 24:3469–3476. [PubMed][CrossRef]
296. Auerbach S, Wright GG. 1955. Studies on immunity in anthrax. VI. Immunizing activity of protective antigen against various strains of Bacillus anthracis. J Immunol 75:129–133. [PubMed]
297. Chawla A, Midha S, Bhatnagar R. 2009. Efficacy of recombinant anthrax vaccine against Bacillus anthracis aerosol spore challenge: preclinical evaluation in rabbits and Rhesus monkeys. Biotechnol J 4:391–399. [PubMed][CrossRef]
298. Klas SD, Petrie CR, Warwood SJ, Williams MS, Olds CL, Stenz JP, Cheff AM, Hinchcliffe M, Richardson C, Wimer S. 2008. A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge. Vaccine 26:5494–5502. [PubMed][CrossRef]
299. Ren J, Dong D, Zhang J, Liu S, Li B, Fu L, Xu J, Yu C, Hou L, Li J, Chen W. 2009. Protection against anthrax and plague by a combined vaccine in mice and rabbits. Vaccine 27:7436–7441. [PubMed][CrossRef]
300. Wimer-Mackin S, Hinchcliffe M, Petrie CR, Warwood SJ, Tino WT, Williams MS, Stenz JP, Cheff A, Richardson C. 2006. An intranasal vaccine targeting both the Bacillus anthracis toxin and bacterium provides protection against aerosol spore challenge in rabbits. Vaccine 24:3953–3963. [PubMed][CrossRef]
301. Galloway DR, Baillie L. 2004. DNA vaccines against anthrax. Expert Opin Biol Ther 4:1661–1667. [PubMed][CrossRef]
302. Keitel WA, Treanor JJ, El Sahly HM, Evans TG, Kopper S, Whitlow V, Selinsky C, Kaslow DC, Rolland A, Smith LR, Lalor PA. 2009. Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults. Hum Vaccin 5:536–544. [PubMed][CrossRef]
303. Hermanson G, Whitlow V, Parker S, Tonsky K, Rusalov D, Ferrari M, Lalor P, Komai M, Mere R, Bell M, Brenneman K, Mateczun A, Evans T, Kaslow D, Galloway D, Hobart P. 2004. A cationic lipid-formulated plasmid DNA vaccine confers sustained antibody-mediated protection against aerosolized anthrax spores. Proc Natl Acad Sci USA 101:13601–13606. [PubMed][CrossRef]
304. Migone TS, Subramanian GM, Zhong J, Healey LM, Corey A, Devalaraja M, Lo L, Ullrich S, Zimmerman J, Chen A, Lewis M, Meister G, Gillum K, Sanford D, Mott J, Bolmer SD. 2009. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med 361:135–144. [PubMed][CrossRef]
305. Mohamed N, Clagett M, Li J, Jones S, Pincus S, D'Alia G, Nardone L, Babin M, Spitalny G, Casey L. 2005. A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge. Infect Immun 73:795–802. [PubMed][CrossRef]
306. Peterson JW, Comer JE, Baze WB, Noffsinger DM, Wenglikowski A, Walberg KG, Hardcastle J, Pawlik J, Bush K, Taormina J, Moen S, Thomas J, Chatuev BM, Sower L, Chopra AK, Stanberry LR, Sawada R, Scholz WW, Sircar J. 2007. Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model. Infect Immun 75:3414–3424. [PubMed][CrossRef]
307. Wycoff KL, Belle A, Deppe D, Schaefer L, Maclean JM, Haase S, Trilling AK, Liu S, Leppla SH, Geren IN, Pawlik J, Peterson JW. Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax. Antimicrob Agents Chemother 55:132–139. [PubMed][CrossRef]
308. Hering D, Thompson W, Hewetson J, Little S, Norris S, Pace-Templeton J. 2004. Validation of the anthrax lethal toxin neutralization assay. Biologicals 32:17–27. [PubMed][CrossRef]
309. Little SF, Ivins BE, Fellows PF, Pitt ML, Norris SL, Andrews GP. 2004. Defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine. Vaccine 22:422–430. [PubMed][CrossRef]
310. Pitt ML, Little SF, Ivins BE, Fellows P, Barth J, Hewetson J, Gibbs P, Dertzbaugh M, Friedlander AM. 2001. In vitro correlate of immunity in a rabbit model of inhalational anthrax. Vaccine 19:4768–4773. [CrossRef]
311. Pittman PR, Norris SL, Barrera Oro JG, Bedwell D, Cannon TL, McKee KT, Jr. 2006. Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series. Vaccine 24:3654–3660. [PubMed][CrossRef]
312. Williamson ED, Hodgson I, Walker NJ, Topping AW, Duchars MG, Mott JM, Estep J, Lebutt C, Flick-Smith HC, Jones HE, Li H, Quinn CP. 2005. Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax. Infect Immun 73:5978–5987. [PubMed][CrossRef]
313. Ingram RJ, Chu KK, Metan G, Maillere B, Doganay M, Ozkul Y, Dyson H, Williamson ED, Baillie L, Kim LU, Ascough S, Sriskandan S, Altmann DM. 2010. An epitope of Bacillus anthracis protective antigen that is cryptic in rabbits may be immunodominant in humans. Infect Immun 78:2353; author reply 2353–2354. [PubMed][CrossRef]
314. Oscherwitz J, Yu F, Cease KB. 2009. A heterologous helper T-cell epitope enhances the immunogenicity of a multiple-antigenic-peptide vaccine targeting the cryptic loop-neutralizing determinant of Bacillus anthracis protective antigen. Infect Immun 77:5509–5518. [PubMed][CrossRef]
315. Oscherwitz J, Yu F, Jacobs JL, Liu TH, Johnson PR, Cease KB. 2009. Synthetic peptide vaccine targeting a cryptic neutralizing epitope in domain 2 of Bacillus anthracis protective antigen. Infect Immun 77:3380–3388. [PubMed][CrossRef]
316. Albrink WS. 1961. Pathogenesis of inhalational anthrax. Bacteriol Rev 25:268–273. [PubMed]
317. Gleiser CA. 1967. Pathology of anthrax infection in animal hosts. Fed Proc 26:1518–1521. [PubMed]
318. Lever MS, Stagg AJ, Nelson M, Pearce P, Stevens DJ, Scott EA, Simpson AJ, Fulop MJ. 2008. Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus). Int J Exp Pathol 89:171–179. [PubMed][CrossRef]
319. Dabisch PA, Kline J, Lewis C, Yeager J, Pitt ML. 2010. Characterization of a head-only aerosol exposure system for nonhuman primates. Inhal Toxicol 22:224–233. [PubMed][CrossRef]
320. Roy CJ, Reed DS, Hutt JA. 2010. Aerobiology and inhalation exposure to biological select agents and toxins. Vet Pathol 47:779–789. [PubMed][CrossRef]
321. Passalacqua KD, Bergman NH. 2006. Bacillus anthracis: interactions with the host and establishment of inhalational anthrax. Future Microbiol 1:397–415. [PubMed][CrossRef]
322. Allerberger F, Grif K, Dierich MP, Wimmer A, Plicka H. 2002. Anthrax inhalation and lethal human infection. Lancet 359:711. doi:10.1016/S0140-6736(02)07793-0. [PubMed][CrossRef]
323. Brachman PS. 1965. Human anthrax in the United States. Antimicrobial Agents Chemother (Bethesda) 5:111–114. [PubMed]
324. Brachman PS. 1970. Anthrax. Ann N Y Acad Sci 174:577–582. [PubMed][CrossRef]
325. Brachman PS. 1980. Inhalation anthrax. Ann N Y Acad Sci 353:83–93. [PubMed][CrossRef]
326. Brachman PS, Fekety FR. 1958. Industrial anthrax. Ann N Y Acad Sci 70:574–584. [PubMed][CrossRef]
327. Friedlander AM. 1999. Clinical aspects, diagnosis and treatment of anthrax. J Appl Microbiol 87:303. doi:10.1046/j.1365-2672.1999.00896.x. [PubMed][CrossRef]
328. Jernigan DB, Raghunathan PL, Bell BP, Brechner R, Bresnitz EA, Butler JC, Cetron M, Cohen M, Doyle T, Fischer M, Greene C, Griffith KS, Guarner J, Hadler JL, Hayslett JA, Meyer R, Petersen LR, Phillips M, Pinner R, Popovic T, Quinn CP, Reefhuis J, Reissman D, Rosenstein N, Schuchat A, Shieh WJ, Siegal L, Swerdlow DL, Tenover FC, Traeger M, Ward JW, Weisfuse I, Wiersma S, Yeskey K, Zaki S, Ashford DA, Perkins BA, Ostroff S, Hughes J, Fleming D, Koplan JP, Gerberding JL. 2002. Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings. Emerg Infect Dis 8:1019–1028. [PubMed][CrossRef]
329. Stern EJ, Uhde KB, Shadomy SV, Messonnier N. 2008. Conference report on public health and clinical guidelines for anthrax. Emerg Infect Dis 14. doi:10.3201/eid1404.070969. [PubMed][CrossRef]
330. Wright M, Team NCAS. 2011. Long-term sequelae in a subset of 2001 anthrax survivors, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Bruges, Belgium, 7 to 11August 2011.
331. Rossi CA, Ulrich M, Norris S, Reed DS, Pitt LM, Leffel EK. 2008. Identification of a surrogate marker for infection in the African green monkey model of inhalation anthrax. Infect Immun 76:5790–5801. [PubMed][CrossRef]
332. Boyer AE, Quinn CP, Hoffmaster AR, Kozel TR, Saile E, Marston CK, Percival A, Plikaytis BD, Woolfitt AR, Gallegos M, Sabourin P, McWilliams LG, Pirkle JL, Barr JR. 2009. Kinetics of lethal factor and poly-D-glutamic acid antigenemia during inhalation anthrax in rhesus macaques. Infect Immun 77:3432–3441. [PubMed][CrossRef]
333. Hoffmaster AR, Meyer RF, Bowen MD, Marston CK, Weyant RS, Thurman K, Messenger SL, Minor EE, Winchell JM, Rassmussen MV, Newton BR, Parker JT, Morrill WE, McKinney N, Barnett GA, Sejvar JJ, Jernigan JA, Perkins BA, Popovic T. 2002. Evaluation and validation of a real-time polymerase chain reaction assay for rapid identification of Bacillus anthracis. Emerg Infect Dis 8:1178–1182. [PubMed][CrossRef]
334. Tang S, Moayeri M, Chen Z, Harma H, Zhao J, Hu H, Purcell RH, Leppla SH, Hewlett IK. 2009. Detection of anthrax toxin by an ultrasensitive immunoassay using europium nanoparticles. Clin Vaccine Immunol 16:408–413. [PubMed][CrossRef]
335. Saile E, Boons GJ, Buskas T, Carlson RW, Kannenberg EL, Barr JR, Boyer AE, Gallegos-Candela M, Quinn CP. 2011. Antibody responses to a spore carbohydrate antigen as a marker of nonfatal inhalation anthrax in rhesus macaques. Clin Vaccine Immunol 18:743–748. [PubMed][CrossRef]
336. Mabry R, Brasky K, Geiger R, Carrion R, Jr, Hubbard GB, Leppla S, Patterson JL, Georgiou G, Iverson BL. 2006. Detection of anthrax toxin in the serum of animals infected with Bacillus anthracis by using engineered immunoassays. Clin Vaccine Immunol 13:671–677. [PubMed][CrossRef]
337. Quinn CP, Dull PM, Semenova V, Li H, Crotty S, Taylor TH, Steward-Clark E, Stamey KL, Schmidt DS, Stinson KW, Freeman AE, Elie CM, Martin SK, Greene C, Aubert RD, Glidewell J, Perkins BA, Ahmed R, Stephens DS. 2004. Immune responses to Bacillus anthracis protective antigen in patients with bioterrorism-related cutaneous or inhalation anthrax. J Infect Dis 190:1228–1236. [PubMed][CrossRef]
338. Modlin JF, Advisory Committee on Immunization Practices. 2000. Use of anthrax vaccine in the United States. Morb Mortal Wkly Rep 49(RR15):1–20. [PubMed]
339. Galen JE, Chinchilla M, Pasetti MF, Wang JY, Zhao L, Arciniega-Martinez I, Silverman DJ, Levine MM. 2009. Mucosal immunization with attenuated Salmonella enterica serovar Typhi expressing protective antigen of anthrax toxin (PA83) primes monkeys for accelerated serum antibody responses to parenteral PA83 vaccine. J Infect Dis 199:326–335. [PubMed][CrossRef]
340. Gochenour WS, Jr, Gleiser CA, Tigertt WD. 1962. Observations on penicillin prophylaxis of experimental inhalation anthrax in the monkey. J Hyg (Lond) 60:29–33. [PubMed][CrossRef]
341. Ivins BE, Pitt ML, Fellows PF, Farchaus JW, Benner GE, Waag DM, Little SF, Anderson GW, Jr, Gibbs PH, Friedlander AM. 1998. Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques. Vaccine 16:1141–1148. [PubMed][CrossRef]
342. Kao LM, Bush K, Barnewall R, Estep J, Thalacker FW, Olson PH, Drusano GL, Minton N, Chien S, Hemeryck A, Kelley MF. 2006. Pharmacokinetic considerations and efficacy of levofloxacin in an inhalational anthrax (postexposure) rhesus monkey model. Antimicrob Agents Chemother 50:3535–3542. [PubMed][CrossRef]
343. Kelly DJ, Chulay JD, Mikesell P, Friedlander AM. 1992. Serum concentrations of penicillin, doxycycline, and ciprofloxacin during prolonged therapy in rhesus monkeys. J Infect Dis 166:1184–1187. [PubMed][CrossRef]
344. Vietri NJ, Purcell BK, Lawler JV, Leffel EK, Rico P, Gamble CS, Twenhafel NA, Ivins BE, Heine HS, Sheeler R, Wright ME, Friedlander AM. 2006. Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax. Proc Natl Acad Sci USA 103:7813–7816. [PubMed][CrossRef]
345. Vietri NJ, Purcell BK, Tobery SA, Rasmussen SL, Leffel EK, Twenhafel NA, Ivins BE, Kellogg MD, Webster WM, Wright ME, Friedlander AM. 2009. A short course of antibiotic treatment is effective in preventing death from experimental inhalational anthrax after discontinuing antibiotics. J Infect Dis 199:336–341. [PubMed][CrossRef]
346. Vitale L, Blanset D, Lowy I, O'Neill T, Goldstein J, Little SF, Andrews GP, Dorough G, Taylor RK, Keler T. 2006. Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity. Infect Immun 74:5840–5847. [PubMed][CrossRef]
347. Ivins BE, Fellows P, Pitt LM, Estep J, Welkos SL, Worsham PL. 1996. Efficacy of a standard human anthrax vaccine against Bacillus anthracis spore challenge in rhesus monkeys. Salisbury Med Bull Suppl:125–126.
348. Pitt LM, Ivins BE, Estep J, Farchaus JW, Friedlander A. 1996. Comparative efficacy of a recombinant protective antigen vaccine against inhalational anthrax in guinea pigs, rabbits, and rhesus monkeys, abstr 96th Annual meeting of the American Society of Microbiology, New Orleans, LA, 19 to 23 May, 1996.
349. Ivins BE, Pitt MLM, Fellows PF, Farchaus JW, Benner GE, Waag DM, Little SF, Anderson GW, Jr, Gibbs PH, Friedlander AM. 1998. Comparative efficacy of experimental anthrax vaccine candidates against inhalational anthrax in rhesus macaques. Vaccine 16:1141–1148. [PubMed][CrossRef]
350. Klinman DM, Klaschik S, Sato T, Tross D. 2009. CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases. Adv Drug Deliv Rev 61:248–255. [PubMed][CrossRef]
351. Nguyen ML, Crowe SR, Kurella S, Teryzan S, Cao B, Ballard JD, James JA, Farris AD. 2009. Sequential B-cell epitopes of Bacillus anthracis lethal factor bind lethal toxin-neutralizing antibodies. Infect Immun 77:162–169. [PubMed][CrossRef]
352. Winterroth L, Rivera J, Nakouzi AS, Dadachova E, Casadevall A. 2010. Neutralizing monoclonal antibody to edema toxin and its effect on murine anthrax. Infect Immun 78:2890–2898. [PubMed][CrossRef]
353. Chabot D, Joyce JG, Caulfield M, Wang S, Vietri NJ, Leffel E, Pitt ML, Cook C, Helper W, Friedlander AM. 2009. Efficacy of a poly-gamma-D-Glutamic acid capsule conjugate vaccine against inhalational anthrax in rabbits and non-human primates, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Santa Fe, New Mexico, 30 August to 3 September 2009.
354. Lincoln RE, Klein F, Walker JS, Haines BW, Jones WI, Mahlandt BG, Friedman RH. 1964. Successful treatment of Rhesus Monkeys for septicemia anthrax. Antimicrob Agents Chemother (Bethesda) 10:759–763. [PubMed]
355. Pitt ML, Dyer D, Washington R, Blanset D, Riddle V, Meldorf M. 2009. Thereapeutic efficacy of Valortim, an anti-toxin monoclonal antibody, in the African green monkey model of inhalational anthrax, abstr Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Santa Fe, New Mexico, 30 August to 3 September 2009.
356. Dyer D, Leffel E, Washington R, Pitt ML. 2009. Development of a therapeutic African Green monkey model for inhalational anthrax to demonstrate added value of adjunct therapies, Bacillus-ACT: The International Conference on Bacillus anthracis, B. cereus, and B. thuringiensis, Santa Fe, New Mexico, 30 August to 3 September 2009.
357. Henning LN, Comer JE, Stark GV, Ray BD, Tordoff KP, Knostman KA, Meister GT. 2012. Development of an inhalational Bacillus anthracis exposure therapeutic model in cynomolgus macaques. Clin Vaccine Immunol 19:1765–1775. [PubMed][CrossRef]
358. Snoy PJ. 2010. Establishing efficacy of human products using animals: the US food and drug administration's “animal rule.” Vet Pathol 47:774–778. [PubMed][CrossRef]
359. Watson LE, Kuo SR, Katki K, Dang T, Park SK, Dostal DE, Tang WJ, Leppla SH, Frankel AE. 2007. Anthrax toxins induce shock in rats by depressed cardiac ventricular function. PLoS One 2:e466. doi:10.1371/journal.pone.0000466. [PubMed][CrossRef]
360. Gupta PK, Moayeri M, Crown D, Fattah RJ, Leppla SH. 2008. Role of N-terminal amino acids in the potency of anthrax lethal factor. PLoS One 3:e3130. doi:10.1371/journal.pone.0003130. [PubMed][CrossRef]
361. Beall FA, Dalldorf FG. 1966. The pathogenesis of the lethal effect of anthrax toxin in the rat. J Infect Dis 116:377–389. [PubMed][CrossRef]
362. Beall FA, Taylor MJ, Thorne CB. 1962. Rapid lethal effect in rats of a third component found upon fractionating the toxin of Bacillus anthracis. J Bacteriol 83:1274–1280. [PubMed]
363. Ezzell JW, Ivins BE, Leppla SH. 1984. Immunoelectrophoretic analysis, toxicity, and kinetics of in vitro production of the protective antigen and lethal factor components of Bacillus anthracis toxin. Infect Immun 45:761–767. [PubMed]
364. Haines BW, Klein F, Lincoln RE. 1965. Quantitative assay for crude anthrax toxins. J Bacteriol 89:74–83. [PubMed]
365. Nye SH, Wittenburg AL, Evans DL, O'Connor JA, Roman RJ, Jacob HJ. 2008. Rat survival to anthrax lethal toxin is likely controlled by a single gene. Pharmacogenomics J 8:16–22. [PubMed][CrossRef]
366. Newman ZL, Printz MP, Liu S, Crown D, Breen L, Miller-Randolph S, Flodman P, Leppla SH, Moayeri M. 2010. Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1. PLoS Pathog 6:e1000906. doi:10.1371/journal.ppat.1000906. [PubMed][CrossRef]
367. Printz MP, Jirout M, Jaworski R, Alemayehu A, Kren V. 2003. Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics. J Appl Physiol 94:2510–2522. [PubMed]
368. Chen Z, Moayeri M, Crown D, Emerson S, Gorshkova I, Schuck P, Leppla SH, Purcell RH. 2009. Novel chimpanzee/human monoclonal antibodies that neutralize anthrax lethal factor, and evidence for possible synergy with anti-protective antigen antibody. Infect Immun 77:3902–3908. [PubMed][CrossRef]
369. Cui X, Li Y, Moayeri M, Choi GH, Subramanian GM, Li X, Haley M, Fitz Y, Feng J, Banks SM, Leppla SH, Eichacker PQ. 2005. Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis. J Infect Dis 191:422–434. [PubMed][CrossRef]
370. Joshi A, Kate S, Poon V, Mondal D, Boggara MB, Saraph A, Martin JT, McAlpine R, Day R, Garcia AE, Mogridge J, Kane RS. 2011. Structure-based design of a heptavalent anthrax toxin inhibitor. Biomacromolecules 12:791–796. [PubMed][CrossRef]
371. Scobie HM, Thomas D, Marlett JM, Destito G, Wigelsworth DJ, Collier RJ, Young JA, Manchester M. 2005. A soluble receptor decoy protects rats against anthrax lethal toxin challenge. J Infect Dis 192:1047–1051. [PubMed][CrossRef]
372. Sharma M, Swain PK, Chopra AP, Chaudhary VK, Singh Y. 1996. Expression and purification of anthrax toxin protective antigen from Escherichia coli. Protein Expr Purif 7:33–38. [PubMed][CrossRef]
373. Sharma S, Thomas D, Marlett J, Manchester M, Young JA. 2009. Efficient neutralization of antibody-resistant forms of anthrax toxin by a soluble receptor decoy inhibitor. Antimicrob Agents Chemother 53:1210–1212. [PubMed][CrossRef]
374. Manayani DJ, Thomas D, Dryden KA, Reddy V, Siladi ME, Marlett JM, Rainey GJ, Pique ME, Scobie HM, Yeager M, Young JA, Manchester M, Schneemann A. 2007. A viral nanoparticle with dual function as an anthrax antitoxin and vaccine. PLoS Pathog 3:1422–1431. [PubMed][CrossRef]
375. Little SF, Webster WM, Fisher DE. 2011. Monoclonal antibodies directed against protective antigen of Bacillus anthracis enhance lethal toxin activity in vivo. FEMS Immunol Med Microbiol 62:11–22. [PubMed][CrossRef]
376. Goossens PL. 2009. Animal models of human anthrax: the Quest for the Holy Grail. Mol Aspects Med 30:467–480. [PubMed][CrossRef]
377. Bolcome RE, 3rd, Sullivan SE, Zeller R, Barker AP, Collier RJ, Chan J. 2008. Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature. Proc Natl Acad Sci USA 105:2439–2444. [PubMed][CrossRef]
378. Fellows PF, Linscott MK, Little SF, Gibbs P, Ivins BE. 2002. Anthrax vaccine efficacy in golden Syrian hamsters. Vaccine 20:1421–1424. [PubMed][CrossRef]
379. Pomerantsev AP, Staritsin NA, Mockov Yu V, Marinin LI. 1997. Expression of cereolysine AB genes in Bacillus anthracis vaccine strain ensures protection against experimental hemolytic anthrax infection. Vaccine 15:1846–1850. [CrossRef]
380. Stepanov AV, Marinin LI, Pomerantsev AP, Staritsin NA. 1996. Development of novel vaccines against anthrax in man. J Biotechnol 44:155–160. [PubMed][CrossRef]
381. Hoffmaster AR, Hill KK, Gee JE, Marston CK, De BK, Popovic T, Sue D, Wilkins PP, Avashia SB, Drumgoole R, Helma CH, Ticknor LO, Okinaka RT, Jackson PJ. 2006. Characterization of Bacillus cereus isolates associated with fatal pneumonias: strains are closely related to Bacillus anthracis and harbor B. anthracis virulence genes. J Clin Microbiol 44:3352–3360. [PubMed][CrossRef]
382. Saile E, Koehler TM. 2006. Bacillus anthracis multiplication, persistence, and genetic exchange in the rhizosphere of grass plants. Appl Environ Microbiol 72:3168–3174. [PubMed][CrossRef]
383. Weiner Z, Glomski I. 2012. Updating perspectives on the initiation of Bacillus anthracis growth and dissemination through its host. Infect Immun 80:1626–1644. [PubMed][CrossRef]
384. Candela T, Dumetz F, Tosi-Couture E, Mock M, Goossens PL, Fouet A. 2012. Cell-wall preparation containing poly-gamma-d-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection. Vaccine 31:171–175. [PubMed][CrossRef]
385. Uchida M, Harada T, Enkhtuya J, Kusumoto A, Kobayashi Y, Chiba S, Shyaka A, Kawamoto K. 2012. Protective effect of Bacillus anthracis surface protein EA1 against anthrax in mice. Biochem Biophys Res Commun 421:323–328. [PubMed][CrossRef]
386. Levy H, Weiss S, Altboum Z, Schlomovitz J, Rothschild N, Glinert I, Sittner A, Kobiler D. 2012. The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits. Microb Pathog 52:55–50. [PubMed][CrossRef]
387. Levy H, Weiss S, Altboum Z, Schlomovitz J, Glinert I, Sittner A, Shafferman A, Kobiler D. 2012. Differential contribution of Bacillus anthracis toxins to pathogenicity in two animal models. Infect Immun 80:2623–2631. [PubMed][CrossRef]
388. Levy H, Glinert I, Weiss S, Sittner A, Schlomovitz J, Altboum Z, Kobiler D. 2014. Toxin-independent virulence of Bacillus anthracis in rabbits. PLoS One 9:e84947. doi:10.1371/journal.pone.0084947. [PubMed][CrossRef]
389. Peachman KK, Li Q, Matyas GR, Shivachandra SB, Lovchik J, Lyons RC, Alving CR, Rao VB, Rao M. 2012. Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores. Clin Vaccine Immunol 19:11–16. [PubMed][CrossRef]
390. Lovchik J, Drysdale M, Koehler T, Hutt J, Lyons CR. 2012. Expression of either lethal toxin or edema toxin by Bacillus anthracis is sufficient for virulence in a rabbit model of inhalational anthrax. Infect Immun 80:2414–2425. [PubMed][CrossRef]
391. Oscherwitz J,Yu F, Cease KB. 2010. A synthetic peptide vaccine directed against the 2β2-2β3 loop of domain 2 of protective antigen protects rabbits from inhalation anthrax. J Immunol 185:3661–3668. [PubMed][CrossRef]
392. Bozue J, Welkos S, Cote CK. The Bacillus anthracis exosporium: what's the big hairy deal? In Eichenberger P, Driks A (ed), The Bacterial Spore: From Molecules to Systems. ASM Press, Washington, DC, in press.
393. Shah A, Liu MC, Vaughan D, Heller AH. 1999. Oral bioequivalence of three ciprofloxacin formulations following single-dose administration: 500 mg tablet compared with 500 mg/10 mL or 500 mg/5 mL suspension and the effect of food on the absorption of ciprofloxacin oral suspension. J Antimicrob Chemother 43(Suppl A):49–54. [PubMed][CrossRef]
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/content/journal/microbiolspec/10.1128/microbiolspec.TBS-0001-2012
2015-02-20
2017-09-21

Abstract:

This article reviews the characteristics of the major animal models utilized for studies on and highlights their contributions to understanding the pathogenesis and host responses to anthrax and its treatment and prevention. Advantages and drawbacks associated with each model, to include the major models (murine, guinea pig, rabbit, nonhuman primate, and rat), and other less frequently utilized models, are discussed. Although the three principal forms of anthrax are addressed, the main focus of this review is on models for inhalational anthrax. The selection of an animal model for study is often not straightforward and is dependent on the specific aims of the research or test. No single animal species provides complete equivalence to humans; however, each species, when used appropriately, can contribute to a more complete understanding of anthrax and its etiologic agent.

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Methods for delivery of by the pulmonary route

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.TBS-0001-2012
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Animal species: comparative use as models

Source: microbiolspec February 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.TBS-0001-2012

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