Bacillus anthracis

Theresa M. Koehler

doi:10.1128/9781555816513.ch54

Chapter 54 : Bacillus anthracis

Author: Theresa M. Koehler

Content Type: Reference

Publication Year: 2006

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555816513

Chapter DOI: 10.1128/9781555816513.ch54

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Abstract:

Prior to the extraordinary interest in Bacillus anthracis generated by the recent bioterrorism events in the United States, much of microbiologists' awareness of the bacterium resulted from its historical significance. B. anthracis can infect all mammals, some birds, and possibly even reptiles. Systemic anthrax, generally resulting from inhalation or ingestion of B. anthracis spores, has a high fatality rate. B. anthracis is a facultative anaerobe and grows in most rich undefined media with a doubling time of approximately 30 min. Experimental studies of anthrax toxin are summarized in this chapter. The majority of animal models for anthrax have been used to assess pathophysiological effects of purified toxin and to test efficacy of vaccines against anthrax. When B. anthracis is grown under appropriate conditions, the outermost surface of vegetative cells is covered by a capsule. As is true for numerous pathogens, the capsule is an important virulence factor. Toxin and capsule synthesis by B. anthracis represents an intriguing example of coordinate expression of virulence genes in response to host-related cues. Major advances in understanding of structure and function of the "classic" virulence factors of B. anthracis, the anthrax toxin proteins and the poly-D-glutamic capsule, combined with new information regarding the anthrax toxin receptors are fueling new strategies for anthrax therapeutics and improved human vaccines. Molecular genetic analyses involving multiple B. anthracis strains will continue to facilitate epidemiological studies and development of advanced methods for detection and identification.

Citation: Koehler T. 2006. Bacillus anthracis, p 659-671. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch54

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Bacillus anthracis

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FIGURE 1

(See the separate color insert for the color version of this illustration.) Ribbon diagrams representing structures of the anthrax toxin proteins. (A) Monomeric PA. Ia (blue), 20-kDa fragment removed with cleavage; Ib (yellow), forms N terminus of PA63 and contains two structural calcium ions (red); II (green), pore formation; III (magenta), oligomerization of PA63; IV (turquoise), receptor binding. (B) LF. Substrate-binding and catalytic domains (green) and PA-binding domain (magenta). (C) EF in complex with calmodulin. Catalytic core (green); PA-binding domain (magenta); helical domain (yellow) interacts with calmodulin (red). (Courtesy of W.-J. Tang.)

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FIGURE 1

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FIGURE 2

(See the separate color insert for the color version of this illustration.) Model of anthrax toxin action. PA binds to receptors TEM8 or CMG2. Following proteolytic cleavage of PA by furin, PA63 oligomerizes to form a heptameric prepore. EF-LF binds to the prepore, and the complex is endocytosed. Acidification of the intracellular compartment triggers translocation of EF and LF to the cytosol. EF, a calmodulin-dependent adenylate cyclase, converts ATP to cAMP. LF, a zinc-dependent protease, cleaves members of the MEK family and may also affect other targets. (Reprinted from Moayeri and Leppla [ 75 ].)

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FIGURE 2

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FIGURE 3

Model depicting B. anthracis virulence gene regulation.

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FIGURE 3

Model depicting B. anthracis virulence gene regulation.

References

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1. Abrami, L.,, S. Liu,, P. Cosson,, S. H. Leppla,, and F. G. van der Goot. 2003. Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J. Cell Biol. 160: 321– 328.

2. Bartkus, J. M.,, and S. H. Leppla. 1989. Transcriptional regulation of the protective antigen gene of Bacillus anthracis. Infect. Immun. 57: 2295– 2300.

3. Battisti, L.,, B. D. Green,, and C. B. Thorne. 1985. Mating system for transfer of plasmids among Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis. J. Bacteriol. 162: 543– 550.

4. Beauregard, K. E.,, R. J. Collier,, and J. A. Swanson. 2000. Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization. Cell. Microbiol. 2: 251– 258.

5. Bourgogne, A.,, M. Drysdale,, S. G. Hilsenbeck,, S. N. Peterson,, and T. M. Koehler. 2003. Global effects of virulence gene regulators in a Bacillus anthracis strain with both virulence plasmids. Infect. Immun. 71: 2736– 2743.

6. Bradley, K. A.,, J. Mogridge,, M. Mourez,, R. J. Collier,, and J. A. Young. 2001. Identification of the cellular receptor for anthrax toxin. Nature 414: 225– 229.

7. Brook, I.,, T. B. Elliott,, R. A. Harding,, S. S. Bouhaouala,, S. J. Peacock,, G. D. Ledney,, and G. B. Knudson. 2001. Susceptibility of irradiated mice to Bacillus anthracis sterne by the intratracheal route of infection. J. Med. Microbiol. 50: 702– 711.

8. Brossier, F.,, M. Levy,, and M. Mock. 2002. Anthrax spores make an essential contribution to vaccine efficacy. Infect. Immun. 70: 661– 664.

9. Brossier, F.,, M. Weber-Levy,, M. Mock,, and J. C. Sirard. 2000. Role of toxin functional domains in anthrax pathogenesis. Infect. Immun. 68: 1781– 1786.

10. Brown, D. P.,, L. Ganova-Raeva,, B. D. Green,, S. R. Wilkinson,, M. Young,, and P. Youngman. 1994. Characterization of spo0A homologues in diverse Bacillus and Clostridium species identifies a probable DNA-binding domain. Mol. Microbiol. 14: 411– 426.

11. Cataldi, A.,, A. Fouet,, and M. Mock. 1992. Regulation of pag gene expression in Bacillus anthracis: use of a pag-lacZ transcriptional fusion. FEMS Microbiol. Lett. 98: 89– 94.

12. Charlton, S.,, A. J. Moir,, L. Baillie,, and A. Moir. 1999. Characterization of the exosporium of Bacillus cereus. J. Appl. Microbiol. 87: 241– 245.

13. Chen, Y.,, F. C. Tenover,, and T. M. Koehler. 2004. β-Lactamase gene expression in a penicillin-resistant Bacillus anthracis strain. Antimicrob. Agents Chemother. 48: 4873– 4877.

14. Collier, R. J.,, and J. A. Young. 2003. Anthrax toxin. Annu. Rev. Cell Dev. Biol. 19: 45– 70.

15. Couture-Tosi, E.,, H. Delacroix,, T. Mignot,, S. Mesnage,, M. Chami,, A. Fouet,, and G. Mosser. 2002. Structural analysis and evidence for dynamic emergence of Bacillus anthracis S-layer networks. J. Bacteriol. 184: 6448– 6456.

16. Dai, Z.,, and T. M. Koehler. 1997. Regulation of anthrax toxin activator gene ( atxA) expression in Bacillus anthracis: Temperature, not CO 2/bicarbonate, affects AtxA synthesis. Infect. Immun. 65: 2576– 2582.

17. Dai, Z.,, J.-C. Sirard,, M. Mock,, and T. M. Koehler. 1995. The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence. Mol. Microbiol. 16: 1171– 1181.

18. Daubenspeck, J. M.,, H. Zeng,, P. Chen,, S. Dong,, C. T. Steichen,, N. R. Krishna,, D. G. Pritchard,, and C. L. Turnbough, Jr. 2004. Novel oligosaccharide side chains of the collagen-like region of BclA, the major glycoprotein of the Bacillus anthracis exosporium. J. Biol. Chem. 279: 30945– 30953.

19. Drum, C. L.,, S. Z. Yan,, J. Bard,, Y. Q. Shen,, D. Lu,, S. Soelaiman,, Z. Grabarek,, A. Bohm,, and W. J. Tang. 2002. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature 415: 396– 402.

20. Drysdale, M.,, A. Bourgogne,, S. G. Hilsenbeck,, and T. M. Koehler. 2004. atxA controls Bacillus anthracis capsule synthesis via acpA and a newly discovered regulator, acpB. J. Bacteriol. 186: 307– 315.

21. Drysdale, M.,, S. Heninger,, J. Hutt,, Y. Chen,, C. R. Lyons,, and T. M. Koehler. 2005. Capsule synthesis by Bacillus anthracis is required for dissemination in murine inhalation anthrax. EMBO J. 24: 221– 227.

22. Duesbery, N. S.,, C. P. Webb,, S. H. Leppla,, V. M. Gordon,, K. R. Klimpel,, T. D. Copeland,, N. G. Ahn,, M. K. Oskarsson,, K. Fukasawa,, K. D. Paull,, and G. F. Vande Woude. 1998. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280: 734– 737.

23. Erwin, J. L.,, L. M. DaSilva,, S. Bavari,, S. F. Little,, A. M. Friedlander,, and T. C. Chanh. 2001. Macrophage-derived cell lines do not express proinflammatory cytokines after exposure to Bacillus anthracis lethal toxin. Infect. Immun. 69: 1175– 1177.

24. Etienne-Toumelin, I.,, J. C. Sirard,, E. Duflot,, M. Mock,, and A. Fouet. 1995. Characterization of the Bacillus anthracis S-layer: cloning and sequencing of the structural gene. J. Bacteriol. 177: 614– 620.

25. Ezzell, J. W., Jr., and T. G. Abshire. 1988. Immunological analysis of cell-associated antigens of Bacillus anthracis. Infect. Immun. 56: 349– 356.

26. Farchaus, J. W.,, W. J. Ribot,, M. B. Downs,, and J. W. Ezzell. 1995. Purification and characterization of the major surface array protein from the avirulent Bacillus anthracis Delta Sterne-1. J. Bacteriol. 177: 2481– 2489.

27. Fouet, A.,, and S. Mesnage. 2002. Bacillus anthracis cell envelope components. Curr. Top. Microbiol. Immunol. 271: 87– 113.

28. Fouet, A.,, O. Namy,, and G. Lambert. 2000. Characterization of the operon encoding the alternative σ B factor from Bacillus anthracis and its role in virulence. J. Bacteriol. 182: 5036– 5045.

29. Friedlander, A. M. 1986. Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J. Biol. Chem. 261: 7123– 7126.

30. Friedlander, A. M.,, R. Bhatnagar,, S. H. Leppla,, L. Johnson,, and Y. Singh. 1993. Characterization of macrophage sensitivity and resistance to anthrax lethal toxin. Infect. Immun. 61: 245– 252.

31. Fritz, D. L.,, N. K. Jaax,, W. B. Lawrence,, K. J. Davis,, M. L. Pitt,, J. W. Ezzell,, and A. M. Friedlander. 1995. Pathology of experimental inhalation anthrax in the rhesus monkey. Lab. Investig. 73: 691– 702.

32. Galloway, D. R.,, and L. Baillie. 2004. DNA vaccines against anthrax. Expert Opin. Biol. Ther. 4: 1661– 1667.

33. Gordon, V. M.,, K. R. Klimpel,, N. Arora,, M. A. Henderson,, and S. H. Leppla. 1995. Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases. Infect. Immun. 63: 82– 87.

34. Green, B. D.,, L. Battisti,, T. M. Koehler,, and C. B. Thorne. 1985. Demonstration of a capsule plasmid in Bacillus anthracis. Infect. Immun. 49: 291– 297.

35. Guidi-Rontani, C.,, M. Levy,, H. Ohayon,, and M. Mock. 2001. Fate of germinated Bacillus anthracis spores in primary murine macrophages. Mol. Microbiol. 42: 931– 938.

36. Guidi-Rontani, C.,, M. Weber-Levy,, E. Labruyere,, and M. Mock. 1999. Germination of Bacillus anthracis spores within alveolar macrophages. Mol. Microbiol. 31: 9– 17.

37. Guignot, J.,, M. Mock,, and A. Fouet. 1997. AtxA activates the transcription of genes harbored by both Bacillus anthracis virulence plasmids. FEMS Microbiol. Lett. 147: 203– 207.

38. Hachisuka, Y.,, K. Kojima,, and T. Sato. 1966. Fine filaments on the outside of the exosporium of Bacillus anthracis spores. J. Bacteriol. 91: 2382– 2384.

39. Hachisuka, Y.,, S. Kozuka,, and M. Tsujikawa. 1984. Exosporia and appendages of spores of Bacillus species. Microbiol. Immunol. 28: 619– 624.

40. Hambleton, P.,, and P. C. Turnbull. 1990. Anthrax vaccine development: a continuing story. Adv. Biotechnol. Processes 13: 105– 122.

41. Hanna, P. 1998. Anthrax pathogenesis and host response. Curr. Top. Microbiol. Immunol. 225: 13– 35.

42. Hanna, P. C.,, D. Acosta,, and R. J. Collier. 1993. On the role of macrophages in anthrax. Proc. Natl. Acad. Sci. USA 90: 10198– 10201.

43. Hill, K. K.,, L. O. Ticknor,, R. T. Okinaka,, M. Asay,, H. Blair,, K. A. Bliss,, M. Laker,, P. E. Pardington,, A. P. Richardson,, M. Tonks,, D. J. Beecher,, J. D. Kemp,, A. B. Kolsto,, A. C. Wong,, P. Keim,, and P. J. Jackson. 2004. Fluorescent amplified fragment length polymorphism analysis of Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis isolates. Appl. Environ. Microbiol. 70: 1068– 1080.

44. Hoffmaster, A. R.,, and T. M. Koehler. 1997. The anthrax toxin activator gene atxA is associated with CO 2-enhanced non-toxin gene expression in Bacillus anthracis. Infect. Immun. 65: 3091– 3099.

45. Hoffmaster, A. R.,, and T. M. Koehler. 1999. Autogenous regulation of the Bacillus anthracis pag operon. J. Bacteriol. 181: 4485– 4492.

46. Hoffmaster, A. R.,, J. Ravel,, D. A. Rasko,, G. D. Chapman,, M. D. Chute,, C. K. Marston,, B. K. De,, C. T. Sacchi,, C. Fitzgerald,, L. W. Mayer,, M. C. Maiden,, F. G. Priest,, M. Barker,, L. Jiang,, R. Z. Cer,, J. Rilstone,, S. N. Peterson,, R. S. Weyant,, D. R. Galloway,, T. D. Read,, T. Popovic,, and C. M. Fraser. 2004. Identification of anthrax toxin genes in a Bacillus cereus associated with an illness resembling inhalation anthrax. Proc. Natl. Acad. Sci. USA 101: 8449– 8454.

47. Hugh-Jones, M. E.,, and V. de Vos. 2002. Anthrax and wildlife. Rev. Sci. Tech. 21: 359– 383.

48. Ireland, J.,, and P. Hanna. 2002. Amino acid- and purine ribonucleoside-induced germination of Bacillus anthracis ΔSterne endospores: gerS mediates responses to aromatic ring structures. J. Bacteriol. 184: 1296– 1303.

49. Ivanova, N.,, A. Sorokin,, I. Anderson,, N. Galleron,, B. Candelon,, V. Kapatral,, A. Bhattacharyya,, G. Reznik,, N. Mikhailova,, A. Lapidus,, L. Chu,, M. Mazur,, E. Goltsman,, N. Larsen,, M. D’Souza,, T. Walunas,, Y. Grechkin,, G. Pusch,, R. Haselkorn,, M. Fonstein,, S. D. Ehrlich,, R. Overbeek,, and N. Kyrpides. 2003. Genome sequence of Bacillus cereus and comparative analysis with Bacillus anthracis. Nature 423: 87– 91.

50. Ivins, B. E.,, S. L. Welkos,, G. B. Knudson,, and D. J. Leblanc. 1988. Transposon Tn916 mutagenesis in Bacillus anthracis. Infect. Immun. 56: 176– 181.

51. Ivins, B. E.,, S. L. Welkos,, G. B. Knudson,, and S. F. Little. 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.

52. Ivins, B. E.,, S. L. Welkos,, S. F. Little,, M. H. Crumrine,, and G. O. Nelson. 1992. Immunization against anthrax with Bacillus anthracis protective antigen combined with adjuvants. Infect. Immun. 60: 662– 668.

53. Jernigan, D. B.,, P. L. Raghunathan,, B. P. Bell,, R. Brechner,, E. A. Bresnitz,, J. C. Butler,, M. Cetron,, M. Cohen,, T. Doyle,, M. Fischer,, C. Greene,, K. S. Griffith,, J. Guarner,, J. L. Hadler,, J. A. Hayslett,, R. Meyer,, L. R. Petersen,, M. Phillips,, R. Pinner,, T. Popovic,, C. P. Quinn,, J. Reefhuis,, D. Reissman,, N. Rosenstein,, A. Schuchat,, W. J. Shieh,, L. Siegal,, D. L. Swerdlow,, F. C. Tenover,, M. Traeger,, J. W. Ward,, I. Weisfuse,, S. Wiersma,, K. Yeskey,, S. Zaki,, D. A. Ashford,, B. A. Perkins,, S. Ostroff,, J. Hughes,, D. Fleming,, J. P. Koplan,, and J. L. Gerberding. 2002. Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings. Emerg. Infect. Dis. 8: 1019– 1028.

54. Keim, P.,, and K. L. Smith. 2002. Bacillus anthracis evolution and epidemiology. Curr. Top. Microbiol. Immunol. 271: 21– 32.

55. Kim, S. O.,, Q. Jing,, K. Hoebe,, B. Beutler,, N. S. Duesbery,, and J. Han. 2003. Sensitizing anthrax lethal toxinresistant macrophages to lethal toxin-induced killing by tumor necrosis factor-alpha. J. Biol. Chem. 278: 7413– 7421.

56. Koehler, T. M.,, Z. Dai,, and M. Kaufman-Yarbray. 1994. Regulation of the Bacillus anthracis protective antigen gene: CO2 and a trans-acting element activate transcription from one of two promoters. J. Bacteriol. 176: 586– 595.

57. Kozel, T. R.,, W. J. Murphy,, S. Brandt,, B. R. Blazar,, J. A. Lovchik,, P. Thorkildson,, A. Percival,, and C. R. Lyons. 2004. mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia. Proc. Natl. Acad. Sci. USA 101: 5042– 5047.

58. Kramer, M. J.,, and I. L. Roth. 1968. Ultrastructural differences in the exosporium of the Sterne and Vollum strains of Bacillus anthracis. Can. J. Microbiol. 14: 1297– 1299.

59. Lai, E. M.,, N. D. Phadke,, M. T. Kachman,, R. Giorno,, S. Vazquez,, J. A. Vazquez,, J. R. Maddock,, and A. Driks. 2003. Proteomic analysis of the spore coats of Bacillus subtilis and Bacillus anthracis. J. Bacteriol. 185: 1443– 1454.

60. Lentner, C. 1981 Geigy Scientific Tables: Units of Measurement, Body Fluids, Composition of the Body, Nutrition, vol. 1 Ciba Geigy, Basel, Switzerland.

61. Leppla, S. H., 1995. Anthrax toxins, p. 543– 572. In J. Moss,, B. Iglewski,, M. Vaughan,, and A. T. Tu (ed.), Bacterial Toxins and Virulence Factors in Disease. Marcel Dekker, New York, N.Y..

62. Little, S. F.,, and G. B. Knudson. 1986. Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig. Infect. Immun. 52: 509– 512.

63. Liu, H.,, N. H. Bergman,, B. Thomason,, S. Shallom,, A. Hazen,, J. Crossno,, D. A. Rasko,, J. Ravel,, T. D. Read,, S. N. Peterson,, J. Yates III,, and P. C. Hanna. 2004. Formation and composition of the Bacillus anthracis endospore. J. Bacteriol. 186: 164– 178.

64. Lyons, C. R.,, J. Lovchik,, J. Hutt,, M. F. Lipscomb,, E. Wang,, S. Heninger,, L. Berliba,, and K. Garrison. 2004. Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility. Infect. Immun. 72: 4801– 4809.

65. Makino, S.,, C. Sasakawa,, I. Uchida,, N. Terakado,, and M. Yoshikawa. 1988. Cloning and CO 2-dependent expression of the genetic region for encapsulation from Bacillus anthracis. Mol. Microbiol. 2: 371– 376.

66. Makino, S.,, M. Watarai,, H. I. Cheun,, T. Shirahata,, and I. Uchida. 2002. Effect of the lower molecular capsule released from the cell surface of Bacillus anthracis on the pathogenesis of anthrax. J. Infect. Dis. 186: 227– 233.

67. Makino, S.-I.,, I. Uchida,, N. Terakado,, C. Sasakawa,, and M. Yoshikawa. 1989. Molecular characterization and protein analysis of the cap region, which is essential for encapsulation in Bacillus anthracis. J. Bacteriol. 171: 722– 730.

68. Marrero, R.,, and S. L. Welkos. 1995. The transformation frequency of plasmids into Bacillus anthracis is affected by adenine methylation. Gene 152: 75– 78.

69. Mesnage, S.,, E. Tosi-Couture,, P. Gounon,, M. Mock,, and A. Fouet. 1998. The capsule and S-layer: two independent and yet compatible macromolecular structures in Bacillus anthracis. J. Bacteriol. 180: 52– 58.

70. Mesnage, S.,, E. Tosi-Couture,, M. Mock,, P. Gounon,, and A. Fouet. 1997. Molecular characterization of the Bacillus anthracis main S-layer component: evidence that it is the major cell-associated antigen. Mol. Microbiol. 23: 1147– 1155.

71. Mignot, T.,, S. Mesnage,, E. Couture-Tosi,, M. Mock,, and A. Fouet. 2002. Developmental switch of S-layer protein synthesis in Bacillus anthracis. Mol. Microbiol. 43: 1615– 1627.

72. Mignot, T.,, M. Mock,, and A. Fouet. 2003. A plasmid-encoded regulator couples the synthesis of toxins and surface structures in Bacillus anthracis. Mol. Microbiol. 47: 917– 927.

73. Milne, J. C.,, D. Furlong,, P. C. Hanna,, J. S. Wall,, and R. J. Collier. 1994. Anthrax protective antigen forms oligomers during intoxication of mammalian cells. J. Biol. Chem. 269: 20607– 20612.

74. Moayeri, M.,, D. Haines,, H. A. Young,, and S. H. Leppla. 2003. Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. J. Clin. Investig. 112: 670– 682.

75. Moayeri, M.,, and S. H. Leppla. 2004. The roles of anthrax toxin in pathogenesis. Curr. Opin. Microbiol. 7: 19– 24.

76. Mogridge, J.,, K. Cunningham,, and R. J. Collier. 2002. Stoichiometry of anthrax toxin complexes. Biochemistry 41: 1079– 1082.

77. Mourez, M.,, D. B. Lacy,, K. Cunningham,, R. Legmann,, B. R. Sellman,, J. Mogridge,, and R. J. Collier. 2002. 2001: a year of major advances in anthrax toxin research. Trends Microbiol. 10: 287– 293.

78. Okinaka, R. T.,, K. Cloud,, O. Hampton,, A. Hoffmaster,, K. K. Hill,, P. Keim,, T. M. Koehler,, G. Lamke,, S. Kumano,, J. Mahillon,, D. Manter,, Y. Martinez,, D. Ricke,, R. Svensson,, and P. J. Jackson. 1999. The sequence and organization of pXO1, the large Bacillus anthracis plasmid harboring the anthrax toxin genes. J. Bacteriol. 181: 6509– 6515.

79. Ooi, Y. M.,, and H. R. Colten. 1979. Genetic defect in secretion of complement C5 in mice. Nature 282: 207– 208.

80. Pannifer, A. D.,, T. Y. Wong,, R. Schwarzenbacher,, M. Renatus,, C. Petosa,, J. Bienkowska,, D. B. Lacy,, R. J. Collier,, S. Park,, S. H. Leppla,, P. Hanna,, and R. C. Liddington. 2001. Crystal structure of the anthrax lethal factor. Nature 414: 229– 233.

81. Park, J. M.,, F. R. Greten,, Z. W. Li,, and M. Karin. 2002. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297: 2048– 2051.

82. Pellizzari, R.,, C. Guidi-Rontani,, G. Vitale,, M. Mock,, and C. Montecucco. 2000. Lethal factor of Bacillus anthracis cleaves the N-terminus of MAPKKs: analysis of the intracellular consequences in macrophages. Int. J. Med. Microbiol. 290: 421– 427.

83. Petosa, C.,, R. J. Collier,, K. R. Klimpel,, S. H. Leppla,, and R. C. Liddington. 1997. Crystal structure of the anthrax toxin protective antigen. Nature 385: 833– 838.

84. Pezard, C.,, P. Berche,, and M. Mock. 1991. Contribution of individual toxin components to virulence of Bacillus anthracis. Infect. Immun. 59: 3472– 3477.

85. Pezard, C.,, M. Weber,, J. C. Sirard,, P. Berche,, and M. Mock. 1995. Protective immunity induced by Bacillus anthracis toxin-deficient strains. Infect. Immun. 63: 1369– 1372.

86. Phipps, A. J.,, C. Premanandan,, R. E. Barnewall,, and M. D. Lairmore. 2004. Rabbit and nonhuman primate models of toxin-targeting human anthrax vaccines. Microbiol. Mol. Biol. Rev. 68: 617– 629.

87. Pitt, M. L.,, S. F. Little,, B. E. Ivins,, P. Fellows,, J. Barth,, J. Hewetson,, P. Gibbs,, M. Dertzbaugh,, and A. M. Friedlander. 2001. In vitro correlate of immunity in a rabbit model of inhalational anthrax. Vaccine 19: 4768– 4773.

88. Priest, F. G.,, M. Barker,, L. W. Baillie,, E. C. Holmes,, and M. C. Maiden. 2004. Population structure and evolution of the Bacillus cereus group. J. Bacteriol. 186: 7959– 7970.

89. Rasko, D. A.,, J. Ravel,, O. A. Okstad,, E. Helgason,, R. Z. Cer,, L. Jiang,, K. A. Shores,, D. E. Fouts,, N. J. Tourasse,, S. V. Angiuoli,, J. Kolonay,, W. C. Nelson,, A. B. Kolsto,, C. M. Fraser,, and T. D. Read. 2004. The genome sequence of Bacillus cereus ATCC 10987 reveals metabolic adaptations and a large plasmid related to Bacillus anthracis pXO1. Nucleic Acids Res. 32: 977– 988.

90. Read, T. D.,, S. N. Peterson,, N. Tourasse,, L. W. Baillie,, I. T. Paulsen,, K. E. Nelson,, H. Tettelin,, D. E. Fouts,, J. A. Eisen,, S. R. Gill,, E. K. Holtzapple,, O. A. Okstad,, E. Helgason,, J. Rilstone,, M. Wu,, J. F. Kolonay,, M. J. Beanan,, R. J. Dodson,, L. M. Brinkac,, M. Gwinn,, R. T. DeBoy,, R. Madpu,, S. C. Daugherty,, A. S. Durkin,, D. H. Haft,, W. C. Nelson,, J. D. Peterson,, M. Pop,, H. M. Khouri,, D. Radune,, J. L. Benton,, Y. Mahamoud,, L. Jiang,, I. R. Hance,, J. F. Weidman,, K. J. Berry,, R. D. Plaut,, A. M. Wolf,, K. L. Watkins,, W. C. Nierman,, A. Hazen,, R. Cline,, C. Redmond,, J. E. Thwaite,, O. White,, S. L. Salzberg,, B. Thomason,, A. M. Friedlander,, T. M. Koehler,, P. C. Hanna,, A. B. Kolsto,, and C. M. Fraser. 2003. The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature 423: 81– 86.

91. Rhie, G. E.,, M. H. Roehrl,, M. Mourez,, R. J. Collier,, J. J. Mekalanos,, and J. Y. Wang. 2003. A dually active anthrax vaccine that confers protection against both bacilli and toxins. Proc. Natl. Acad. Sci. USA 100: 10925– 10930.

92. Ross, J. M. 1957. Pathogenesis of anthrax following administration of spores by the respiratory route. J. Pathol. Bacteriol. 73: 485– 494.

93. Ruthel, G.,, W. J. Ribot,, S. Bavari,, and T. A. Hoover. 2004. Time-lapse confocal imaging of development of Bacillus anthracis in macrophages. J. Infect. Dis. 189: 1313– 1316.

94. Saile, E.,, and T. M. Koehler. 2002. Control of anthrax toxin gene expression by the transition state regulator abrB. J. Bacteriol. 184: 370– 380.

95. Salles, I. I.,, A. E. Tucker,, D. E. Voth,, and J. D. Ballard. 2003. Toxin-induced resistance in Bacillus anthracis lethal toxin-treated macrophages. Proc. Natl. Acad. Sci. USA 100: 12426– 12431.

96. Schneerson, R.,, J. Kubler-Kielb,, T. Y. Liu,, Z. D. Dai,, S. H. Leppla,, A. Yergey,, P. Backlund,, J. Shiloach,, F. Majadly,, and J. B. Robbins. 2003. Poly(γ-D-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of Bacillus anthracis: a potential addition to the anthrax vaccine. Proc. Natl. Acad. Sci. USA 100: 8945– 8950.

97. Scobie, H. M.,, G. J. Rainey,, K. A. Bradley,, and J. A. Young. 2003. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc. Natl. Acad. Sci. USA 100: 5170– 5174.

98. Shafa, F.,, B. J. Moberly,, and P. Gerhardt. 1966. Cytological features of anthrax spores phagocytized in vitro by rabbit alveolar macrophages. J. Infect. Dis. 116: 401– 413.

99. Sirard, J.-C.,, M. Mock,, and A. Fouet. 1995. Molecular tools for the study of transcriptional regulation in Bacillus anthracis. Res. Microbiol. 146: 729– 737.

100. Sirard, J.-C.,, M. Mock,, and A. Fouet. 1994. The three Bacillus anthracis toxin genes are coordinately regulated by bicarbonate and temperature. J. Bacteriol. 176: 5188– 5192.

101. Smith, H. 2000. Discovery of the anthrax toxin: the beginning of in vivo studies on pathogenic bacteria. Trends Microbiol. 8: 199– 200.

102. Steichen, C.,, P. Chen,, J. F. Kearney,, and C. L. Turnbough, Jr. 2003. Identification of the immunodominant protein and other proteins of the Bacillus anthracis exosporium. J. Bacteriol. 185: 1903– 1910.

103. Sterne, M. 1939. The use of anthrax vaccines prepared from avirulent (uncapsulated) variants of Bacillus anthracis. Onderstepoort J. Vet. Sci. Anim. Ind. 13: 307– 312.

104. Sylvestre, P.,, E. Couture-Tosi,, and M. Mock. 2002. A collagen-like surface glycoprotein is a structural component of the Bacillus anthracis exosporium. Mol. Microbiol. 45: 169– 178.

105. Sylvestre, P.,, E. Couture-Tosi,, and M. Mock. 2003. Polymorphism in the collagen-like region of the Bacillus anthracis BclA protein leads to variation in exosporium filament length. J. Bacteriol. 185: 1555– 1563.

106. Thorne, C. B., 1993. Bacillus anthracis, p. 113– 124. In A. L. Sonenshein,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics. American Society for Microbiology, Washington, D.C..

107. Thorne, C. B., 1985. Genetics of Bacillus anthracis, p. 56– 62. In L. Leive (ed.), Microbiology. American Society for Microbiology, Washington, D.C..

108. Tinsley, E.,, A. Naqvi,, A. Bourgogne,, T. M. Koehler,, and S. A. Khan. 2004. Isolation of a minireplicon of the virulence plasmid pXO2 of Bacillus anthracis and characterization of the plasmid-encoded RepS replication protein. J. Bacteriol. 186: 2717– 2723.

109. Todd, S. J.,, A. J. Moir,, M. J. Johnson,, and A. Moir. 2003. Genes of Bacillus cereus and Bacillus anthracis encoding proteins of the exosporium. J. Bacteriol. 185: 3373– 3378.

110. Turnbull, P. C. 1991. Anthrax vaccines: past, present and future. Vaccine 9: 533– 539.

111. Turnbull, P. C. 1991. Bacillus, p. 233– 245. In S. Baron (ed.), Medical Microbiology, 4th ed. The University Medical Branch at Galveston, Galveston, Tex..

112. Turnbull, P. C.,, R. A. Hutson,, M. J. Ward,, M. N. Jones,, C. P. Quinn,, N. J. Finnie,, C. J. Duggleby,, J. M. Kramer,, and J. Melling. 1992. Bacillus anthracis but not always anthrax. J. Appl. Bacteriol. 72: 21– 28.

113. Turnbull, P. C. B. (ed.). 1996. Proceedings of the International Workshop on Anthrax, vol. 87, special supplement. Salisbury Medical Society, Salisbury, United Kingdom.

114. Uchida, I.,, J. M. Hornung,, C. B. Thorne,, K. R. Klimpel,, and S. H. Leppla. 1993. Cloning and characterization of a gene whose product is a trans-activator of anthracis toxin synthesis. J. Bacteriol. 175: 5329– 5338.

115. Uchida, I.,, S. Makino,, C. Sasakawa,, M. Yoshikawa,, C. Sugimoto,, and N. Terakado. 1993. Identification of a novel gene, dep, associated with depolymerization of the capsular polymer in Bacillus anthracis. Mol. Microbiol. 9: 487– 496.

116. Vietri, N. J.,, R. Marrero,, T. A. Hoover,, and S. L. Welkos. 1995. Identification and characterization of a trans-activator involved in the regulation of encapsulation by Bacillus anthracis. Gene 152: 1– 9.

117. Vitale, G.,, R. Pellizzari,, C. Recchi,, G. Napolitani,, M. Mock,, and C. Montecucco. 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.

118. Wang, T. T.,, P. F. Fellows,, T. J. Leighton,, and A. H. Lucas. 2004. Induction of opsonic antibodies to the gamma-D-glutamic acid capsule of Bacillus anthracis by immunization with a synthetic peptide-carrier protein conjugate. FEMS Immunol. Med. Microbiol. 40: 231– 237.

119. Watters, J. W.,, K. Dewar,, J. Lehoczky,, V. Boyartchuk,, and W. F. Dietrich. 2001. Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor. Curr. Biol. 11: 1503– 1511.

120. Watters, J. W.,, and W. F. Dietrich. 2001. Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11. Genomics 73: 223– 231.

121. Welkos, S. L.,, T. J. Keener,, and P. H. Gibbs. 1986. Differences in susceptibility of inbred mice to Bacillus anthracis. Infect. Immun. 51: 795– 800.

122. Wesche, J.,, J. L. Elliott,, P. O. Falnes,, S. Olsnes,, and R. J. Collier. 1998. Characterization of membrane translocation by anthrax protective antigen. Biochemistry 37: 15737– 15746.

123. Whiting, G. C.,, S. Rijpkema,, T. Adams,, and M. J. Corbel. 2004. Characterisation of adsorbed anthrax vaccine by two-dimensional gel electrophoresis. Vaccine 22: 4245– 4251.