Chair, Herbert L. and Margaret W. DuPont Distinguished Professor in Biomedical Science,
Department of Microbiology and Molecular Genetics
Education & Training
- Postdoctoral Fellow
- Harvard Medical School
- University of Massachusetts, 1987
Dr. Koehler is Chair of the Department of Microbiology and Molecular Genetics at McGovern Medical School. She holds the Herbert L. and Margaret W. DuPont Distinguished Professor in Biomedical Science and is a faculty member of the UTH Graduate School of Biomedical Sciences. Dr. Koehler came to the Medical School as an assistant professor in 1991 following a postdoctoral fellowship at Harvard Medical School. She earned her M.S. and Ph.D. degrees in Microbiology at the University of Massachusetts – Amherst and her B.S. in Biology at Virginia Tech.
Dr. Koehler studies host-pathogen interactions and signaling among the Bacillus cereus group species. Her NIH-funded research program focuses on Bacillus anthracis. She is especially interested in relationships between bacterial physiology and virulence and she is an internationally recognized anthrax expert.
Koehler has received many commendations for excellence in research and education. In 2008, she became a Fellow of the American Academy of Microbiology in recognition of her outstanding contributions to the science and profession of microbiology. In 2009, she was awarded the Paul E. Darlington Award from the Graduate School for outstanding mentoring of graduate students. Dr. Koehler is an associate editor of PLoS Pathogens and a member of the Editorial Board of the Journal of Bacteriology. She has chaired multiple national and international scientific conferences and served on several federal advisory committees. She currently chairs the NIH Review Group on Bacterial Pathogenesis.
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.
Pflughoeft KJ, Swick MC, Engler DA, Yeo HJ, Koehler TM. 2014. Modulation of the Bacillus anthracis secretome by the immune inhibitor A1 protease. J Bacteriol. 196(2):424-35.
Dale, J.L. and Koehler, T.M. 2013. Virulence Gene Regulation in Bacillus anthracis and Other Bacillus cereus Group Species. In: Regulation of Bacterial Virulence, Vasil, M. and Darwin, A. (eds.) ASM Press.
Dale JL, Raynor MJ, Dwivedi P, Koehler TM. 2012. cis-Acting elements that control expression of the master virulence regulatory gene atxA in Bacillus anthracis. J Bacteriol. 194(15):4069-79.
Lovchik JA, Drysdale M, Koehler TM, Hutt JA, Lyons CR. 2012. Expression of either lethal toxin or edema toxin by Bacillus anthracis is sufficient for virulence in a rabbit model of inhalational anthrax. Infect Immun 80(7):2414-25.
Hammerstrom TG, Roh JH, Nikonowicz EP, Koehler TM. 2011. Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO2 -signaling. Mol Microbiol. 82(3):634-47.