Research Interest: Pathogenesis of Pulmonary Bacterial Pathogen Infection
Ph.D.: University of Oklahoma, Norman, Oklahoma
Postdoctoral: National Institutes of Health, Rocky Mountain Laboratories, Laboratory of Intracellular Parasites, Hamilton, Montana
The Voth laboratory uses novel human-derived models of infection to study bacterial pathogens that establish pulmonary infections in humans. The first pathogen of interest, Coxiella burnetii, causes human Q fever, which typically presents as an acute debilitating flu-like disease complicated by pneumonia. However, chronic infection can occur and normally manifests as life-threatening endocarditis. In humans, Coxiella replicates to high numbers in alveolar macrophages and secretes proteins using a type IV secretion system to manipulate its host cell. We have identified multiple secreted Coxiella proteins, and are using multiple approaches to identify host proteins that interact with Coxiella proteins and define 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 primary alveolar macrophage signaling. Coxiella actively inhibits macrophage death during intracellular growth by activating the pro-survival host proteins Akt, Erk1/2, and PKA. Additionally, we are exploring the role of p62 and the Nrf2 antioxidant pathway in preventing the oxidative stress response to infection. The second pathogen of interest, Staphylococcus aureus, is a versatile bacterium that uses numerous toxins to cause disease. Staphylococcal pneumonia is a severe manifestation of disease and we are using our ovel human lung tissue and primary pulmonary cell models to investigate the intracellular survival of this opportunistic pathogen and the toxins required for lung infection. Collectively, our studies will provide novel insight into the complex interplay between intracellular bacterial pathogens and the host lung.
- Fullerton, M.S., Colonne, P.M,, Dragan, A.L., Brann, K.R., Kurten, R.C., Voth, D.E. Neurotransmitter System-Targeting Drugs Antagonize Growth of the Q Fever Agent, Coxiella burnetii, in Human Cells. mSphere. 2021 Jul 7:e0044221. doi: 10.1128/mSphere.00442-21. Online ahead of print.
- Dragan, A.L., Voth, D.E. Take my breath away: studying pathogen invasion of the human lung using primary tissue models. Pathog Dis. 2021 Mar 31;79(4):ftab016. doi: 10.1093/femspd/ftab016. PMID: 33734371; PMCID: PMC8012110.
- Dragan, A.L., Voth, D.E. (2020) Coxiella burnetii: international pathogen of mystery. Microbes Infect. 22(3):100-110.
- Brann, K.R., Fullerton, M.S., and Voth, D.E. (2020). Coxiella burnetii Requires Host Eukaryotic Initiation Factor 2α Activity for Efficient Intracellular Replication. Infect Immun. 88(7):e00096-20.
- Brann, K.R., Fullerton, M.S., Onyilagha, F.I., Prince, A.A., Kurten, R.C., Rom, J.S., Blevins, J.S., Smeltzer, M.S., Voth, D.E. 2019. Infection of Primary Human Alveolar Macrophages Alters Staphylococcus aureus Toxin Production and Activity. Infect Immun. 20;87(7). pii: e00167-19.
- Winchell, C.G., Dragan, A.L., Doiron, K.R., Onyilagha, F.I., Kurten, R.C., and D.E. Voth (2018) Coxiella burnetii Subverts p62/Sequestosome 1 and Activates Nrf2 Signaling in Human Macrophages. Infection and Immunity. 86:e00608-17.
- Colonne, P.M., Winchell, C.G., Graham, J.G., Onyilagha, F.I., MacDonald, L.J., Doeppler, H.R., Storz, P., Kurten, R.C., Beare, P.A., Heinzen, R.A., and D.E. Voth (2016) Vasodilator-Stimulated Phosphoprotein Activity is Required for Coxiella burnetii Growth in Human Macrophages. PLoS Pathogens. 12:e1005915.
- Graham, J.G., Winchell, C.G., Kurten, R.C., and D.E. Voth (2016) Development of an ex vivo Tissue Platform to Study the Human Lung Response to Coxiella burnetii. Infection and Immunity. 84:1438-1445.
- Winchell, C.G., Graham, J.G., Kurten, R.C., and D.E. Voth (2014) Coxiella burnetii Type IV Secretion-Dependent Recruitment of Macrophage Autophagosomes. Infection and Immunity. 82:2229-2238.