The University of Texas Medical School at Houston
Department of Microbiology and Molecular Genetics

Theresa M. Koehler, Ph.D.

Back

  • Chair
  • Theresa M. Koehler, Ph.D.Herbert L. and Margaret W. DuPont Distinguished Professor in Biomedical Science
  • 2009, Paul E. Darlington Mentor Award Recipient
  • Department of Microbiology &
    Molecular Genetics
  • University of Texas-Houston Medical School
    6431 Fannin Street, MSB 1.192
    Houston, Texas 77030
  • Telephone: (713) 500-5450
    Laboratory Telephone: (713) 500-5451
    e-mail: theresa.m.koehler@uth.tmc.edu

Education:

Ph.D., University of Massachusetts, 1987

Postdoctoral Fellow, Harvard Medical School

Research Interests:

Bacillus cereus group species: Genetics, Physiology, and Host Interactions

Bacillus anthracis, a Gram-positive spore-forming soil bacterium and member of the Bacillus cereus group species, is distinguished by its ability to cause anthrax in mammals. Depending upon the route of entry, infection with spores can result in cutaneous disease, which is readily treatable with antibiotics, or systemic disease, which is often fatal. The continuing worldwide incidence of anthrax in animal populations, risk of human infection associated with animal outbreaks, and potential for use of B. anthracis as a biological weapon, warrant continued investigation of this organism and its virulence mechanisms.

Virulence of B. anthracis is associated with synthesis of the anthrax toxin proteins, protective antigen, lethal factor, and edema factor, and an antiphagocytic capsule composed of poly-D-glutamic acid. Our work focuses on the genetic basis for expression of the structural genes for the toxin proteins, pagA, lef, and cya, the capsule biosynthesis operon, capBCAD, and other genes with a known or suspected role in virulence. The toxin genes are located on pXO1 (182-kb), while the capsule genes are found on pXO2 (93-kb).

The model for virulence gene regulation in B. anthracis is of growing complexity and includes numerous trans-acting regulators. The most critical and far-reaching regulator is atxA, a pXO1 gene that appears to be unique to the species. atxA is essential for expression of all toxin genes, contributes to control of the capsule operon, and affects expression of numerous chromosomal genes. We are establishing the molecular functions and epistatic relationships of atxA and other regulators. Using a mouse model for inhalation anthrax, we are evaluating gene expression and development in vivo, including spatial and temporal measurements of germination and dissemination.

In related studies, we are examining the relatedness of B. anthracis to the closely-related, but less harmful species, B. cereus and B. thuringiensis. The three species are very similar physiologically and genetically, yet they cause vastly different diseases. With certain important exceptions, key differences in gene expression, as opposed to genetic content, may result in the differing pathogenesis associated with these species.

We are also interested in the B. anthracis lifecycle outside of the mammalian host. We are studying B. anthracis germination and multiplication in the soil, particularly in association with the plant rhizosphere. These investigations have implications for genetic exchange between B. anthracis and other soil organisms and for detection of the bacterium in the environment.

Selected Publications:

  • Hammerstrom TJ, Roh JH, Nikonowicz EP, Koehler TM.: Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2)-signaling. Mol. Microbiol. 2011 Nov;82(3):634-47. [abstract]
  • Pflughoeft KJ, Sumby P, Koehler TM.: Bacillus anthracis sin locus and regulation of secreted proteases. J. Bacteriol. 2011 Feb;193(3):631-9. [abstract]
  • Ross CL, Thomason KS, and Koehler TM.: An Extra-cytoplasmic function sigma factor controls b-lactamase gene expression in Bacillus anthracis and other B. cereus group species. J Bacteriol. 2009 Nov;191(21):6683-93. [abstract]
  • Koehler TM. (2009) Bacillus anthracis physiology and genetics. Mol. Aspects Med. 2009 Dec;30(6):386-96. [abstract]
  • McGillivray SM, Ebrahimi CM, Fisher N, Sabet M, Zhang DX, Chen Y, Haste NM, Aroian RV, Gallo RL, Guiney DG, Friedlander AM, Koehler TM, Nizet V. ClpX contributes to innate defense peptide resistance and virulence phenotypes of Bacillus anthracis. J. Innate Immun. 2009 Aug;1(5):494-506.[abstract]
  • Barua S, McKevitt M, DeGiusti K, Hamm EE, Larabee J, Shakir S, Bryant K, Koehler TM, Blanke SR, Dyer D, Gillaspy A, Ballard JD. The mechanism of Bacillus anthracis intracellular germination requires multiple and highly diverse genetic loci. Infect Immun. 2009 Jan;77(1):23-31.[abstract]
  • Chand HS, Drysdale M, Lovchik J, Koehler TM, Lipscomb MF, Lyons CR. (2009) Discriminating virulence mechanisms among Bacillus strains by using a murine subcutaneous infection model. Infect Immun. 77:429-35. [abstract]
  • Lisanby MW, Swiecki MK, Dizon BL, Pflughoeft KJ, Koehler TM, Kearney JF. (2008) Cathelicidin administration protects mice from Bacillus anthracis spore challenge. J Immunol. 181:4989-5000. [abstract]
  • Hadjifrangiskou M, Koehler TM. (2008) Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters. Microbiology. 154:2501-12. [abstract]
  • [Search PubMed for more papers by Theresa Koehler]