VIRULENCE GENE EXPRESSION BY BACILLUS ANTHRACIS

Summary

Principal Investigator: THERESA KOEHLER
Affiliation: Texas Medical Center
Country: USA
Abstract: DESCRIPTION (Adapted from the applicant's abstract): To be successful pathogens, bacteria must possess mechanisms for sensing specific host environments, processing changes, and making appropriate adaptations. In many bacteria, expression of disparate virulence factors is controlled by a common regulatory system. Virulence gene expression in Bacillus anthracis, the causative agent of anthrax, is a unique example of a coordinately regulated response to a specific host-related signal. Virulent Bacillus anthracis produce two known virulence factors, a tripartite toxin, composed of edema factor, lethal factor, and protective antigen, and a poly-D-glutamic acid capsule. The toxin and capsule genes are located on plasmids pXO1 (185 kb) and pXO2 (95 kb), respectively. Synthesis of these virulence factors is enhanced when B. anthracis is grown in elevated levels of carbon dioxide. CO2 is postulated to be a physiologically significant signal during anthrax infection. Concentrations of bicarbonate and CO2 in mammalian tissues are comparable to those that activate toxin and capsule synthesis during in vitro growth. The long term goal of these studies is to elucidate the molecular basis for virulence gene expression in B. anthracis. The PI has determined that the trans-acting regulatory gene atxA is required for CO2-induced transcription of all three toxin genes during growth in vitro. AtxA also activates toxin expression in vivo; atxA mutants are avirulent in mice and mice infected with atxA- strains show a decreased immunological response to the toxin proteins. Another gene, acpA, has been implicated in CO2-induced capsule gene expression. In this study, the PI will further probe regulation of toxin and capsule synthesis and investigate whether B. anthracis harbors additional virulence genes. The specific aims are to: 1) identify atxA-regulated non-toxin genes and test the effect of these genes on virulence; 2) identify and characterize additional regulatory genes that affect toxin expression, 3) investigate the physiological significance of acpA expression in cells harboring atxA. These studies will provide information relevant to the pathogenesis of anthrax disease and increase knowledge concerning host-parasite relationships and signal transduction.
Funding Period: 1992-12-01 - 2003-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters
    Maria Hadjifrangiskou
    Department of Microbiology and Molecular Genetics, University of Texas Houston Health Science Center, 6431 Fannin Street, Houston, TX 77030, USA
    Microbiology 154:2501-12. 2008
  2. pmc Bacillus anthracis physiology and genetics
    Theresa M Koehler
    Department of Microbiology and Molecular Genetics, The University of Texas, Houston Health Science Center, Houston, TX, United States
    Mol Aspects Med 30:386-96. 2009
  3. pmc An extracytoplasmic function sigma factor controls beta-lactamase gene expression in Bacillus anthracis and other Bacillus cereus group species
    Cana L Ross
    Department of Microbiology and Molecular Genetics, University of Texas Houston Medical School, Houston, Texas 77030, USA
    J Bacteriol 191:6683-93. 2009
  4. pmc ClpX contributes to innate defense peptide resistance and virulence phenotypes of Bacillus anthracis
    Shauna M McGillivray
    Department of Pediatrics, University of California San Diego, La Jolla, CA 92093 0687, USA
    J Innate Immun 1:494-506. 2009
  5. pmc cis-Acting elements that control expression of the master virulence regulatory gene atxA in Bacillus anthracis
    Jennifer L Dale
    Department of Microbiology and Molecular Genetics, The University Texas Health Science Center Houston Medical School, Houston, Texas, USA
    J Bacteriol 194:4069-79. 2012
  6. pmc Modulation of the Bacillus anthracis secretome by the immune inhibitor A1 protease
    Kathryn J Pflughoeft
    Department of Microbiology and Molecular Genetics, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
    J Bacteriol 196:424-35. 2014
  7. pmc Bacillus anthracis sin locus and regulation of secreted proteases
    Kathryn J Pflughoeft
    Department of Microbiology and Molecular Genetics, University of Texas, Houston Health Science Center, 6431 Fannin St, MSB 1 508, Houston, TX 77030, USA
    J Bacteriol 193:631-9. 2011
  8. pmc Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling
    Troy G Hammerstrom
    Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Medical School, Houston, TX, USA
    Mol Microbiol 82:634-47. 2011

Detail Information

Publications8

  1. ncbi Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters
    Maria Hadjifrangiskou
    Department of Microbiology and Molecular Genetics, University of Texas Houston Health Science Center, 6431 Fannin Street, Houston, TX 77030, USA
    Microbiology 154:2501-12. 2008
    ..These findings suggest that the structural topology of the DNA plays an important role in the control of anthrax toxin gene expression...
  2. pmc Bacillus anthracis physiology and genetics
    Theresa M Koehler
    Department of Microbiology and Molecular Genetics, The University of Texas, Houston Health Science Center, Houston, TX, United States
    Mol Aspects Med 30:386-96. 2009
    ..cereus group. The developmental nature of B. anthracis and its pathogenic (mammalian host) and environmental (soil) lifestyles of make it an interesting model for study of niche-specific bacterial gene expression and physiology...
  3. pmc An extracytoplasmic function sigma factor controls beta-lactamase gene expression in Bacillus anthracis and other Bacillus cereus group species
    Cana L Ross
    Department of Microbiology and Molecular Genetics, University of Texas Houston Medical School, Houston, Texas 77030, USA
    J Bacteriol 191:6683-93. 2009
    ..anthracis contains the genes necessary for sensing beta-lactam antibiotics, the B. anthracis sigP and rsiP gene products are not sufficient for bla induction...
  4. pmc ClpX contributes to innate defense peptide resistance and virulence phenotypes of Bacillus anthracis
    Shauna M McGillivray
    Department of Pediatrics, University of California San Diego, La Jolla, CA 92093 0687, USA
    J Innate Immun 1:494-506. 2009
    ..We conclude that ClpX is an important factor allowing B. anthracis to subvert host immune clearance mechanisms, and thus represents a novel therapeutic target for prevention or therapy of anthrax, a foremost biodefense concern...
  5. pmc cis-Acting elements that control expression of the master virulence regulatory gene atxA in Bacillus anthracis
    Jennifer L Dale
    Department of Microbiology and Molecular Genetics, The University Texas Health Science Center Houston Medical School, Houston, Texas, USA
    J Bacteriol 194:4069-79. 2012
    ..Notably, an atxA promoter mutant that produced elevated levels of AtxA and toxin proteins during culture was unaffected for virulence in a murine model for anthrax...
  6. pmc Modulation of the Bacillus anthracis secretome by the immune inhibitor A1 protease
    Kathryn J Pflughoeft
    Department of Microbiology and Molecular Genetics, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
    J Bacteriol 196:424-35. 2014
    ..anthracis secretome itself. ..
  7. pmc Bacillus anthracis sin locus and regulation of secreted proteases
    Kathryn J Pflughoeft
    Department of Microbiology and Molecular Genetics, University of Texas, Houston Health Science Center, 6431 Fannin St, MSB 1 508, Houston, TX 77030, USA
    J Bacteriol 193:631-9. 2011
    ..Our data are consistent with a model in which InhA1 protease levels are controlled at the transcriptional level by SinR and at the posttranslational level by camelysin...
  8. pmc Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling
    Troy G Hammerstrom
    Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Medical School, Houston, TX, USA
    Mol Microbiol 82:634-47. 2011
    ....