1887

Abstract

The Gram-positive, spore-forming pathogen is the aetiological agent of anthrax. Its main virulence factors are two toxins and an anti-phagocytic capsule. When is grown in laboratory culture, the highest expression of the anthrax toxin genes occurs during entry into stationary phase, suggesting that nutrient limitation is an environmental cue which induces toxin production. A common bacterial response to starvation is the so-called stringent response, in which the hyperphosphorylated guanosine nucleotide (p)ppGpp is the effector molecule. In , and other bacteria, accumulation of this molecule leads to down-regulation of stable RNA synthesis and upregulation of the expression of genes involved in survival under nutrient-poor conditions. This study focuses on the stringent response of . We show that in the gene is responsible for the synthesis of (p)ppGpp and the stringent down-regulation of stable RNA synthesis upon starvation for the essential amino acids isoleucine, leucine and valine. The deletion of did not affect the expression of the virulence gene or virulence in a mouse model of infection. In contrast, spore counts upon growth and sporulation in a defined medium were approximately 10 000-fold lower for the deletion mutant than for the parental strain. The contribution of the stringent response to efficient sporulation of is notable, as this suggests that the stringent response may contribute to the persistence of in the natural environment.

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2007-12-01
2020-09-23
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References

  1. Bourgogne A., Drysdale M., Hilsenbeck S. G., Peterson S. N., Koehler T. M.. 2003; Global effects of virulence gene regulators in a Bacillus anthracis strain with both virulence plasmids. Infect Immun71:2736–2743
    [Google Scholar]
  2. Braeken K., Moris M., Daniels R., Vanderleyden J., Michiels J.. 2005; New horizons for (p)ppGpp in bacterial and plant physiology. Trends Microbiol14:45–54
    [Google Scholar]
  3. Buono F., Testa R., Lundgren D. G.. 1966; Physiology of growth and sporulation in Bacillus cereus . I. Effect of glutamic and other amino acids. J Bacteriol91:2291–2299
    [Google Scholar]
  4. Candela T., Fouet A.. 2005; Bacillus anthracis CapD, belonging to the γ -glutamyltranspeptidase family, is required for the covalent anchoring of capsule to peptidoglycan. Mol Microbiol57:717–726
    [Google Scholar]
  5. Candela T., Mock M., Fouet A.. 2005; CapE, a 47-amino-acid peptide, is necessary for Bacillus anthracis polyglutamate capsule synthesis. J Bacteriol187:7765–7772
    [Google Scholar]
  6. Cashel M., Gentry D. R., Hernandez V. J., Vinella D.. others 1996; The stringent response. In Escherichia coli and Salmonella: Cellular and Molecular Biology , 2nd edn. pp1458–1496 Edited by Neidhardt F. C. Washington, DC: American Society for Microbiology;
  7. Dahl J. L., Kraus C. N., Boshoff H. I., Doan B., Foley K., Avarbock D., Kaplan G., Mizrahi V., Rubin H., Barry C. E. III. 2003; The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci U S A100:10026–10031
    [Google Scholar]
  8. Dragon D. C., Bader D. E., Mitchell J., Woollen N.. 2005; Natural dissemination of Bacillus anthracis spores in northern Canada. Appl Environ Microbiol71:1610–1615
    [Google Scholar]
  9. Eymann C., Mittenhuber G., Hecker M.. 2001; The stringent response, σ H-dependent gene expression and sporulation in Bacillus subtilis . Mol Gen Genet264:913–923
    [Google Scholar]
  10. Fouet A., Mock M.. 1996; Differential influence of the two Bacillus anthracis plasmids on regulation of virulence gene expression. Infect Immun64:4928–4932
    [Google Scholar]
  11. Fouet A., Mock M.. 2006; Regulatory networks for virulence and persistence of Bacillus anthracis . Curr Opin Microbiol9:160–166
    [Google Scholar]
  12. Gimenez A. P., Wu Y. Z., Paya M., Delclaux C., Touqui L., Goossens P. L.. 2004; High bactericidal efficiency of type IIA phospholipase A2 against Bacillus anthracis and inhibition of its secretion by the lethal toxin. J Immunol173:521–530
    [Google Scholar]
  13. Green B. D., Battisti L., Koehler T. M., Thorne C. B.. 1985; Demonstration of a capsule plasmid in Bacillus anthracis . Infect Immun49:291–297
    [Google Scholar]
  14. Guidi-Rontani C., Weber-Levy M., Labruyere E., Mock M.. 1999; Germination of Bacillus anthracis spores within alveolar macrophages. Mol Microbiol31:9–17
    [Google Scholar]
  15. Guignot J., Mock M., Fouet A.. 1997; AtxA activates the transcription of genes harbored by both Bacillus anthracis virulence plasmids. FEMS Microbiol Lett147:203–207
    [Google Scholar]
  16. Hadjifrangiskou M., Chen Y., Koehler T. M.. 2007; The alternative sigma factor σ H is required for toxin gene expression by Bacillus anthracis . J Bacteriol189:1874–1883
    [Google Scholar]
  17. Jensen G. B., Hansen B. M., Eilenberg J., Mahillon J.. 2003; The hidden lifestyles of Bacillus cereus and relatives. Environ Microbiol5:631–640
    [Google Scholar]
  18. Kasai K., Nishizawa T., Takahashi K., Hosaka T., Aoki H., Ochi K.. 2006; Physiological analysis of the stringent response elicited in an extreme thermophilic bacterium, Thermus thermophilus . J Bacteriol188:7111–7122
    [Google Scholar]
  19. Lemos J. A., Brown T. A. Jr, Burne R. A.. 2004; Effects of RelA on key virulence properties of planktonic and biofilm populations of Streptococcus mutans . Infect Immun72:1431–1440
    [Google Scholar]
  20. Lewis P. J., Thaker S. D., Errington J.. 2000; Compartmentalization of transcription and translation in Bacillus subtilis . EMBO J19:710–718
    [Google Scholar]
  21. Mignot T., Mock M., Fouet A.. 2003; A plasmid-encoded regulator couples the synthesis of toxins and surface structures in Bacillus anthracis . Mol Microbiol47:917–927
    [Google Scholar]
  22. Mittenhuber G.. 2001; Comparative genomics and evolution of genes encoding bacterial (p)ppGpp synthetases/hydrolases (the Rel, RelA and SpoT proteins. J Mol Microbiol Biotechnol3:585–600
    [Google Scholar]
  23. Mock M., Fouet A.. 2001; Anthrax. Annu Rev Microbiol55:647–671
    [Google Scholar]
  24. Ochi K.. 1987; Changes in nucleotide pools during sporulation of Streptomyces griseus in submerged culture. J Gen Microbiol133:2787–2795
    [Google Scholar]
  25. Ochi K., Kandala J. C., Freese E.. 1981; Initiation of Bacillus subtilis sporulation by the stringent response to partial amino acid deprivation. J Biol Chem256:6866–6875
    [Google Scholar]
  26. Pezard C., Berche P., Mock M.. 1991; Contribution of individual toxin components to virulence of Bacillus anthracis . Infect Immun59:3472–3477
    [Google Scholar]
  27. Read T. D., Peterson S. N., Tourasse N., Baillie L. W., Paulsen I. T., Nelson K. E., Tettelin H., Fouts D. E., Eisen J. A.. other authors 2003; The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature423:81–86
    [Google Scholar]
  28. Reed L. J., Muench H.. 1938; A simple method of estimating fifty percent endpoints. Am J Hyg27:493–497
    [Google Scholar]
  29. Saile E., Koehler T. M.. 2002; Control of anthrax toxin gene expression by the transition state regulator abrB . J Bacteriol184:370–380
    [Google Scholar]
  30. Saile E., Koehler T. M.. 2006; Bacillus anthracis multiplication, persistence, and genetic exchange in the rhizosphere of grass plants. Appl Environ Microbiol72:3168–3174
    [Google Scholar]
  31. Sirard J. C., Mock M., Fouet A.. 1994; The three Bacillus anthracis toxin genes are coordinately regulated by bicarbonate and temperature. J Bacteriol176:5188–5192
    [Google Scholar]
  32. Strauch M. A., Ballar P., Rowshan A. J., Zoller K. L.. 2005; The DNA-binding specificity of the Bacillus anthracis AbrB protein. Microbiology151:1751–1759
    [Google Scholar]
  33. Taylor C. M., Beresford M., Epton H. A., Sigee D. C., Shama G., Andrew P. W., Roberts I. S.. 2002; Listeria monocytogenes relA and hpt mutants are impaired in surface-attached growth and virulence. J Bacteriol184:621–628
    [Google Scholar]
  34. Trieu-Cuot P., Courvalin P.. 1983; Nucleotide sequence of the Streptococcus faecalis plasmid gene encoding the 3′5′′-aminoglycoside phosphotransferase type III. Gene23:331–341
    [Google Scholar]
  35. Trieu-Cuot P., Carlier C., Martin P., Courvalin P.. 1987; Plasmid transfer by conjugation from Escherichia coli to Gram-positive bacteria. FEMS Microbiol Lett48:289–294
    [Google Scholar]
  36. Tsvetanova B., Wilson A. C., Bongiorni C., Chiang C., Hoch J. A., Perego M.. 2007; Opposing effects of histidine phosphorylation regulate the AtxA virulence transcription factor in Bacillus anthracis . Mol Microbiol63:644–655
    [Google Scholar]
  37. Uchida I., Hornung J. M., Thorne C. B., Klimpel K. R., Leppla S. H.. 1993; Cloning and characterization of a gene whose product is a trans -activator of anthrax toxin synthesis. J Bacteriol175:5329–5338
    [Google Scholar]
  38. Van Ness G. B.. 1971; Ecology of anthrax. Science172:1303–1307
    [Google Scholar]
  39. Welkos S. L., Vietri N. J., Gibbs P. H.. 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 Pathog14:381–388
    [Google Scholar]
  40. Wendrich T. M., Marahiel M. A.. 1997; Cloning and characterization of a relA/spoT homologue from Bacillus subtilis . Mol Microbiol26:65–79
    [Google Scholar]
  41. White A. K., Hoch J. A., Grynberg M., Godzik A., Perego M.. 2006; Sensor domains encoded in Bacillus anthracis virulence plasmids prevent sporulation by hijacking a sporulation sensor histidine kinase. J Bacteriol188:6354–6360
    [Google Scholar]
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