Dr. Koehler, Chair Emerita of the Department of Microbiology and Molecular Genetics, came to McGovern Medical School as an assistant professor in 1991, following a postdoctoral fellowship at Harvard Medical School. She earned her B.S. in Biology from Virginia Tech, and M.S. and Ph.D. in Microbiology from the University of Massachusetts.
Dr. Koehler is an elected Fellow of the American Academy of Microbiology in recognition of her outstanding contributions to the science and profession of microbiology. Her research expertise is in bacterial genetics and physiology. She is an internationally recognized anthrax expert, and her NIH-funded research program on Bacillus anthracis spans more than 30 years. Dr. Koehler’s NIH service includes chairing the Bacterial Pathogenesis study section, membership and chair positions on several Special Emphasis grant review panels, and membership on several other committees of the NIH Center for Scientific Review.
Dr. Koehler is passionate about graduate student, medical student, and postdoctoral fellow training. She served as the Director of an NIH T32 training grant, and is an awardee of the Paul E. Darlington Award from the M.D. Anderson UTHealth Graduate School for Biomedical Sciences for outstanding mentoring of graduate students.
Dr. Koehler has chaired numerous national and international scientific conferences and served on the editorial board of multiple journals. She has been a member of several advisory boards for state and federal science committees, including the National Science Advisory Board for Biosecurity. She was President of the Association of Medical School Microbiology and Immunology Chairs, leading professional development conferences to connect chairs from over 100 medical schools in the U.S., Canada, and Mexico. She is currently President-elect of the American Society for Microbiology (ASM), which seeks to promote and advance the microbial sciences through education, advocacy, and professional development. With over 30,000 members, the ASM is one of the largest life sciences societies in the world.
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. Dr. Koehler’s work focused 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. Dr. Koehler’s research group established molecular functions and epistatic relationships of atxA and other regulators. Using a mouse model for inhalation anthrax, their studies examined gene expression and development in vivo, including spatial and temporal measurements of germination and dissemination.
In related studies, the Koehler lab examined 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.
Dr. Koehler’s research team also investigated the B. anthracis lifecycle outside of the mammalian host. They demonstrated 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.
Corsi ID, Koehler TM.: Overlapping and Distinct Functions of the Paralogous PagR Regulators of Bacillus anthracis. J. Bacteriol. 2022 Aug 25:e0020822. Online ahead of print. PMID: 36005808.
Dutta S, Corsi ID, Bier N, Koehler TM.: BrnQ-Type Branched-Chain Amino Acid Transporters Influence Bacillus anthracis Growth and Virulence. mBio 13(1):e0364021. 2022 PMID: 35073743.
Bier, N., Hammerstrom, T.G., Koehler, T.M.: Influence of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System on Toxin Gene Expression and Virulence in Bacillus anthracis. Molec. Microbiol. 113:237-252. 2020. PMID: 31667937.
Raynor, M.J., Roh, J.H., Widen, S.G., Wood, T.G., and Koehler, T.M.: Regulons and Protein-Protein Interactions of PRD-containing Bacillus anthracis Virulence Regulators Reveal Overlapping but Distinct Functions. Molec. Microbiol. 109:1-22. 2018. PMID: 29603836.
Dale, J.L., Raynor, M.J., Ty, M.C., Hadjifrangiskou, M. Koehler, T.M.: A dual role for the Bacillus anthracis master virulence regulator AtxA: control of sporulation and anthrax toxin production. Frontiers in Microbiol. 9:482-494. 2018. PMCID: PMC2795285.
Scarff, J.M., Raynor, M.J., Seldina, Y.I., Ventura, C.L., Koehler, T.M., and O’Brien, A.D.: The Roles of AtxA orthologues in virulence of anthrax-like Bacillus cereus G9241. Molec. Microbiol. 102:545-561. 2016.
Terwilliger, A., Swick, M.C., Pflughoeft, K.J., Lovchik, J.A., Pomerantsev, A., Lyons, C.R., Koehler, T.M., and Maresso, A.: Bacillus anthracis overcomes an amino acid auxotrophy by cleaving host serum proteins. J. Bacteriol. 197:2400-2411. 2015. PMID: 25962917.
Hammerstrom, T.G., Horton, L.B., Swick, M.C., Joachimiak, A., Osipuik, J., and Koehler, T.M.: Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity. Molec. Microbiol. 95:426-41. 2015.
Charlton-Ouw, K.M., Kubrusly, F., Sandhu, H.K., Swick, M.C., Leake, S.S., Gulbis, B.D., Koehler, T.M., Safi, H.J.: In vitro efficacy of antibiotic beads in treating abdominal vascular graft infections. J. Vascular Surgery. 2014. Apr 15. pii: S0741-5214(14)00653-3. 2014. PMID: 24745942.