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Daniel E. Voth, Ph.D.
Assistant Professor, Department of Microbiology & Immunology Research Interest: Pathogenesis of Coxiella burnetii infection Ph.D.: University of Oklahoma, Norman, Oklahoma Postdoctoral: National Institutes of Health, Rocky Mountain Laboratories, Laboratory of Intracellular Parasites, Hamilton, Montana Phone: (501)
686-8050 Research Description The research in my laboratory focuses on Coxiella burnetii, an obligate intracellular bacterial pathogen that causes human Q fever. Q fever generally presents as an acute debilitating influenzae-like disease. However, chronic infection can occur and normally manifests as life-threatening endocarditis. In the host, Coxiella initially infects alveolar macrophages, where the pathogen directs formation of an intracellular replication vacuole with characteristics of host lysosomes. Coxiella replicates to high numbers in this normally degradative compartment and produces proteins to manipulate the host cell throughout a lengthy infectious cycle. Coxiella produces a Dot/Icm type IV secretion system (T4SS) that is used to deliver bacterial proteins directly to the host cytoplasm where they can potentially interact with a variety of host components. However, due to a lack of methods to genetically manipulate the organism, Coxiella virulence factors remain largely uncharacterized. Using the closely-related intracellular bacterium Legionella pneumophila as a surrogate delivery system, we have identified multiple Coxiella proteins that are translocated by the Dot/Icm T4SS. We are currently using a combination of molecular biology, cell biology, and biochemistry techniques to identify host proteins that interact with Coxiella Dot/Icm substrates and examine the host processes affected. These studies will provide needed information about the arsenal of proteins used by Coxiella for successful parasitism of host cells. We are also studying the impact of Coxiella infection on macrophage signaling. We have found that Coxiella actively inhibits macrophage death during intracellular growth, in part, by activating the pro-survival host proteins Akt and Erk1/2. We are currently examining the impact of these and other pathways on Coxiella infection and the pathogen proteins responsible for this regulation. Collectively, our studies will provide new insight into the complex interplay between intracellular bacterial pathogens and the host. References Omsland, A., Gilk, S. D., Shannon, J. G., Beare, P. A., Voth, D. E., Howe, D., Cockrell, D. C., and Heinzen, R. A. (2009) Exploring the cause of human Q fever: recent advances in Coxiella burnetii research. In Georgiev, V. (Ed.): National Institute of Allergy and Infectious Diseases: Intramural Research (vol. 3), New York, Springer-Verlag. In press. Voth, D.E., Howe, D., Beare, P.A., Vogel, J.P., Unsworth, N., Samuel, J.E., and R.A. Heinzen. The Coxiella burnetii Ankyrin Repeat Domain-Containing Protein Family is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion. Journal of Bacteriology. 191: 4232-4242. Beare, P.A., Samuel, J.E., Omsland, A., Voth, D.E., Kupko, J., Seshardi, R., Massaka, N., Unsworth, N., William, K., Sobral, B., Porcella, S.F., and R.A. Heinzen (2009) Comparative Genomics Reveal Extensive Transposon-Mediated Genomic Plasticity and Diversity Among Potential Effector Proteins Within the Genus Coxiella. Infection and Immunity. 77: 642-656. Gilk, S.D., Voth, D.E., and R.A. Heinzen (2009) Coxiella . (Review for Intracellular Niches of Pathogens - A Microbe's Guide Through the Host Cell). Wiley-VCH. (In press) Voth, D.E. and R.A. Heinzen (2009) Coxiella Type IV Secretion and Cellular Microbiology. Current Opinion in Microbiology. 12:1-7. Voth, D.E. and R.A. Heinzen (2009) Sustained Activation of Akt and Erk1/2 is Required for Coxiella burnetii Anti-Apoptotic Activity. Infection and Immunity. 77:205-213 . Voth, D.E., Howe, D., and R.A. Heinzen (2007) Coxiella burnetii Inhibits Apoptosis in Human THP-1 Cells and Primary Monkey Alveolar Macrophages. Infection and Immunity. 75:4263-4271. Voth, D.E. and R.A. Heinzen (2007) Lounging in a Lysosome: The Intracellular Lifestyle of Coxiella burnetii. Cellular Microbiology. 9:829-840. Coleman, S.A., Fischer, E.R., Cockrell, D.C., Voth, D.E., Howe, D., Mead, D.J., Samuel, J.E., and R.A. Heinzen (2007) Proteome and Antigen Profiling of Coxiella burnetii Developmental Forms. Infection and Immunity. 75:290-298.
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