Skip to main content

Bacillus anthracis Genetics and Virulence Gene Regulation

  • Chapter
Book cover Anthrax

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 271))

Abstract

The Bacillus anthracis genome consists of an approximately 5.3-Mb chromosome and two plasmids, pXO1 (182 kb) and pXO2 (96 kb). Genetic analysis has focused primarily on the structural genes for the anthrax toxin proteins, pagA, lef, and cya, the biosynthetic genes for capsule synthesis, capB, capC, and capA, and a gene associated with depolymerization of capsule, dep. The three toxin genes are located at distinct loci on pXO1, while the cap and dep genes are arranged in an apparent operon on pXO2. Additional genes that may play a role in B. anthracis virulence include the germination operon gerX and the general stress transcription factor sigB. Host-related signals affecting transcription of the toxin and capsule genes include temperature (37°C) and bicarbonate/CO2. The B. anthracis plasmids carry two regulatory genes that share little sequence similarity with regulators in other bacteria. The pXO1-encoded gene atxA positively controls expression of the toxin and capsule genes, and has been implicated in control of other genes of unknown function. atxA mutants are avirulent in mice, and mice infected with atxA-null strains show a decreased immunological response to the toxin proteins. The pXO2-encoded regulator, acpA, shares sequence similarity with atxA. Yet acpA function appears to be restricted to positive control of capsule gene expression. The chromosomal gene abrB, a homologue of a well-characterized B. subtilis transition state regulator, controls growth phase-specific transcription of the toxin genes. Genetic manipulation of B. anthracis can be achieved by using natural means of DNA transfer and by electroporation of recombinant DNAs into B. anthracis. Genetic exchange can occur between B. anthracis strains and between B. anthracis and closely-related species. Although pXO1 and pXO2 are not self-transmissible, these plasmids and others can be transferred by conjugative plasmids originating in B. thuringiensis. Generalized transducing phage that permit inter-species transfer of chromosomal and plasmid DNA have also been described.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Baillie L, Moir A, Manchee R (1998) The expression of the protective antigen of Bacillus anthracis in Bacillus subtilis. J Appl Microbiol 84: 741–746

    Article  PubMed  CAS  Google Scholar 

  • Bartkus JM, Leppla SH (1989) Transcriptional regulation of the protective antigen gene of Bacillus anthracis. Infect Immun 57: 2295–2300

    PubMed  CAS  Google Scholar 

  • Battisti L, Green BD, Thorne CB (1985) Mating system for transfer of plasmids among Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis. J Bacteriol 162: 543–550

    PubMed  CAS  Google Scholar 

  • Bragg TS, Robertson DL (1989) Nucleotide sequence and analysis of the lethal factor gene (lef) from Bacillus anthracis. Gene 81: 45–54

    Article  PubMed  CAS  Google Scholar 

  • Brown DP, Ganova-Raeva L, Green BD, Wilkinson SR, Young M, Youngman P (1994) Characterization of spo0A homologues in diverse Bacillus and Clostridium species identifies a probable DNA-binding domain. Mol Microbiol 14: 411–426

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Dai Z, Koehler TM. (1997) Regulation of anthrax toxin activator gene (atxA) expression in Bacillus anthracis: Temperature, not CO2/bicarbonate, affects AtxA synthesis. Infect Immun 65: 2576–2582

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Dunny GM, Winans SC (1999) Cell-cell signaling in bacteria. Washington, DC: ASM Press

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Fouet A, Sirard JC, Mock M (1994) Bacillus anthracis pXO1 virulence plasmid encodes a type 1 DNA topoisomerase. Mol Microbiol 11: 471–479

    Google Scholar 

  • Green BD, Battisti L, Koehler TM, Thorne CB (1985) Demonstration of a capsule plasmid in Bacillus anthracis. Infect Immun 49: 291–297

    PubMed  CAS  Google Scholar 

  • Green BD, Battisti L, Thorne CB (1989) Involvement of Tn4430 in transfer of Bacillus anthracis plasmids mediated by Bacillus thuringiensis plasmid pXO12. J Bacteriol 171: 104–113

    PubMed  CAS  Google Scholar 

  • Guidi-Rontani C, Pereira Y, Ruffie S, Sirard JC, Weber-Levy M, Mock M (1999a) Identification and characterization of a germination operon on the virulence plasmid pXO1 of Bacillus anthracis. Mol Microbiol 33: 407–414

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Helman JD, Moran CP (2002) RNA polymerase and sigma factors. In: Bacillus subtilis and its close relatives. Sonenshein AL, Hoch JA and Losick R (eds) Washington, DC: ASM Press, pp. 289–312

    Google Scholar 

  • Hoffmaster AR, Koehler TM (1997) The anthrax toxin activator gene atxA is associated with CO2-enhanced non-toxin gene expression in Bacillus anthracis. Infect Immun 65: 3091–3099

    PubMed  CAS  Google Scholar 

  • Hoffmaster AR, Koehler TM (1999) Autogenous regulation of the Bacillus anthracis pag operon. J Bacteriol 181: 4485–4492

    PubMed  CAS  Google Scholar 

  • Iv ins 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  CAS  Google Scholar 

  • Koehler TM (2000) Bacillus anthracis. In: Gram-positive pathogens. Fischetti VA, Novick RP, Ferretti JJ, Protnoy DA and Rood JI (eds) Washington, DC: ASM Press, pp 519–528

    Google Scholar 

  • Koehler TM, Dai Z, Kaufman-Yarbray M (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

    PubMed  CAS  Google Scholar 

  • Koehler TM, Thorne CB (1987) Bacillus subtilis (natto) plasmid pLS20 mediates interspecies plasmid transfer. J Bacteriol 169: 5271–5278

    Google Scholar 

  • Leppla SH (1988) Production and purification of anthrax toxin. Methods Enzymol 165: 103–116

    Article  PubMed  CAS  Google Scholar 

  • Leppla SH (1991) Purification and characterization of adenylyl cyclase from Bacillus anthracis. Methods Enzymol 195: 153–168

    Article  PubMed  CAS  Google Scholar 

  • Makino S, Sasakawa C, Uchida I, Terakado N,Yoshikawa M (1988) Cloning and CO2-dependent expression of the genetic region for encapsulation from Bacillus anthracis. Mol Microbiol 2: 371–376

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Marrero R, Welkos SL (1995) The transformation frequency of plasmids into Bacillus anthracis is affected by adenine methylation. Gene 152: 75–78

    Article  PubMed  CAS  Google Scholar 

  • McIver KS, Heath AS, Green BD, Scott JR (1995) Specific binding of the activator Mga to promoter sequences of the emm and scpA genes in the group A streptococcus. J Bacteriol 177: 6619–6624

    PubMed  CAS  Google Scholar 

  • Mikesell P, Ivins BE, Ristroph JD, Dreier TM (1983) Evidence for plasmid-mediated toxin production in Bacillus anthracis. Infect Immun 39: 371–376

    PubMed  CAS  Google Scholar 

  • Mock M, Labruyere E, Glaser P, Danchin A, Ullmann A (1988) Cloning and expression of the calmodulin-sensitive Bacillus anthracis adenylate cyclase in Escherichia coli. Gene 64: 277–284

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • O’Reilly M, Devine KM (1997) Expression of AbrB, a transition state regulator from Bacillus subtilis, is growth phase dependent in a manner resembling that of Fis, the nucleoid binding protein from Escherichia coli. J Bacteriol 179: 522–529

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Robertson DL, Bragg TS, Simpson S, Kaspar R, Xie W, Tippetts MT (1990) Mapping and characterization of Bacillus anthracis plasmids pXO1 and pXO2. Salisbury Med Bull 68 (Spec Suppl): 55–58

    Google Scholar 

  • Robertson DL, Tippetts MT, Leppla SH (1988) Nucleotide sequence of the Bacillus anthracis edema factor gene (cya): a calmodulin-dependent adenylate cyclase. Gene 73: 363–371

    Article  PubMed  CAS  Google Scholar 

  • Saile E, Koehler TM (2002) Control of anthrax toxin gene expression by the transition state regulator abrB. J Bacteriol 184: 370–380

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Strauch MA (1993) Abr, a transition state regulator. In: Bacillus subtilis and other gram-positive bacteria. Sonenshein AL, Hoch JA and Losick R (eds) Washington, DC: ASM Press, pp 757–764

    Google Scholar 

  • Strauch MA (1995) Delineation of AbrB-binding sites on the Bacillus subtilis spo0H, kinB, ftsAZ, and pbpE promoters and use of a derived homology to identify a previously unsuspected binding site in the bsuB1 methylase promoter. J Bacteriol 177: 6999–7002

    PubMed  CAS  Google Scholar 

  • Thorne CB (1993) Bacillus anthracis. In: Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics. Sonenshein AL, Hoch JA and Losick R (eds) Washington, DC: American Society for Microbiology, pp 113–124

    Google Scholar 

  • Tippetts MT, Robertson DL (1988) Molecular cloning and expression of the Bacillus anthracis edema factor toxin gene: a calmodulin-dependent adenylate cyclase. J Bacteriol 170: 2263–2266

    PubMed  CAS  Google Scholar 

  • Trieu-Cuot P, Carlier C, Poyart-Salmeron C, Courvalin P (1991) Shuttle vectors containing a multiple cloning site and a lacZ alpha gene for conjugal transfer of DNA from Escherichia coli to gram-positive bacteria. Gene 102: 99–104

    Article  PubMed  CAS  Google Scholar 

  • Uchida I, Hashimoto K, Makino S, Sasakawa C,Yoshikawa M, Terakado N (1987) Restriction map of a capsule plasmid of Bacillus anthracis. Plasmid 18: 178–181

    CAS  Google Scholar 

  • Uchida I, Hornung JM, Thorne CB, Klimpel KR, and Leppla SH (1993 a) Cloning and characterization of a gene whose product is a trans-activator of anthracis toxin synthesis. J Bacteriol 175: 5329–5338

    Google Scholar 

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

    Google Scholar 

  • Uchida I, Makino S, Sekizaki T, Terakado N (1997) Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis. Mol Microbiol 23: 1229–1240

    Article  PubMed  CAS  Google Scholar 

  • Uchida I, Sekizaki T, Hashimoto K, Terakado N (1985) Association of encapsulation of Bacillus anthracis with a 60 megadalton plasmid. J Gen Microbiol 131: 363–367

    PubMed  CAS  Google Scholar 

  • Vietri NJ, Marrero R, Hoover TA, Welkos SL (1995) Identification and characterization of a trans-activator involved in the regulation of encapsulation by Bacillus anthracis. Gene 152: 1–9

    Article  PubMed  CAS  Google Scholar 

  • Vodkin MH, Leppla SH (1983) Cloning of the protective antigen gene of Bacillus anthracis. Cell 34: 693–697

    Article  PubMed  CAS  Google Scholar 

  • Welkos SL,Lowe JR, Eden-McCutchan F,Vodkin M,Leppla SH,Schmidt JJ (1988) Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis. Gene 69: 287–300

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Koehler, T.M. (2002). Bacillus anthracis Genetics and Virulence Gene Regulation. In: Koehler, T.M. (eds) Anthrax. Current Topics in Microbiology and Immunology, vol 271. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-05767-4_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-05767-4_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-07799-9

  • Online ISBN: 978-3-662-05767-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics