Thomas C. Zahrt, PhD

Professor

Locations

Microbiology & Immunology
TBRC C3970

Contact Information

General Interests

Bacterial Pathogenesis and Host-Cell Interactions

Education

PhD, Microbiology, University of Illinois, Urbana, 1997

Learn more about the Zahrt Lab

                
                    Research Experience
                
                    Adaptation, Physiological
Gene Expression Regulation, Bacterial
Host-Pathogen Interactions
Latent Tuberculosis
Lipid Droplet Associated Proteins
Lipid Droplets
Mycobacterium tuberculosis
Signal Transduction
Virulence

                    Methodologies and Techniques
                
                    Blotting, Western
Cloning, Molecular
Disease Models, Animal
Electrophoresis, Polyacrylamide Gel
Electrophoretic Mobility Shift Assay
Genetic Complementation Test
Genetic Engineering
Mutagenesis, Insertional
Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Survival Analysis

                    Leadership Positions
                
                    Director, Interdisciplinary Program in Biomedical Sciences
Director, Microbiology and Immunology Graduate Program
Member, Center for Infectious Disease Research

                    Educational Expertise
                
                    Latent Tuberculosis
Lipid Droplets
Mycobacterium tuberculosis
Stress, Physiological

Research Interests

My research interests include the study of Mycobacterium tuberculosis and the mechanisms by which this organism establishes, maintains, and reactivates from persistent (latent) infection. To investigate these processes, our laboratory utilizes several Mycobacterial model systems and a variety of in vitro and in vivo techniques. Through these studies, we hope to identify determinants and pathways important for regulating survival of M. tuberculosis within the host.

One primary area of focus in the laboratory is the study of two-component signal transduction systems and the downstream determinants regulated by these systems. MprAB is a two-component system that mediates resistance to cell envelope stress and is required by M. tuberculosis for persistent infection within the host. More than 100 determinants are regulated by MprAB including two stress-responsive sigma factors (SigE and SigE), an HtrA-like serine protease (PepD), and genes encoding a predicted phage shock protein system (Psp). Interestingly, we have found that phage shock protein A (PspA), an important component of this system, binds intracytoplasmic lipid droplets when they are produced by Mycobacterium under conditions of stress. Lipid droplets are fatty acid storage compartments which contain a neutral fatty acid core and which are surrounded by a phospholipid monolayer and proteins. Lipid droplets are thought to be the primary energy source utilized by M. tuberculosis during latency when the bacterium exists within granulomatous lesion.

Our recent studies have demonstrated that PspA associates with lipid droplets using an amphipathic helix that is present at the N-terminus of the protein. Loss or overproduction of PspA alters the size distribution of lipid droplets produced, and negatively impacts the ability of Mycobacterium to survive under conditions of non-replicating persistence. Current studies are focused on understanding the molecular mechanism by which PspA regulates these activities and determining whether other proteins play a role in lipid droplet homeostasis and Mycobacterial persistence during latency.

Association of Mycobacterium Proteins with Lipid Droplets.

(Armstrong RM, Carter DC, Atkinson SN, Terhune SS, Zahrt TC.) J Bacteriol. 2018 08 15;200(16) PMID: 29760207 PMCID: PMC6060360 SCOPUS ID: 2-s2.0-85050494395 05/16/2018
Rv2744c Is a PspA Ortholog That Regulates Lipid Droplet Homeostasis and Nonreplicating Persistence in Mycobacterium tuberculosis.

(Armstrong RM, Adams KL, Zilisch JE, Bretl DJ, Sato H, Anderson DM, Zahrt TC.) J Bacteriol. 2016 06 01;198(11):1645-1661 PMID: 27002134 PMCID: PMC4959298 03/24/2016
The MprB extracytoplasmic domain negatively regulates activation of the Mycobacterium tuberculosis MprAB two-component system.

(Bretl DJ, Bigley TM, Terhune SS, Zahrt TC.) J Bacteriol. 2014 Jan;196(2):391-406 PMID: 24187094 PMCID: PMC3911260 11/05/2013
Mechanisms of Francisella tularensis intracellular pathogenesis.

(Celli J, Zahrt TC.) Cold Spring Harb Perspect Med. 2013 Apr 01;3(4):a010314 PMID: 23545572 PMCID: PMC3683997 SCOPUS ID: 2-s2.0-84879000118 04/03/2013
MprA and DosR coregulate a Mycobacterium tuberculosis virulence operon encoding Rv1813c and Rv1812c.

(Bretl DJ, He H, Demetriadou C, White MJ, Penoske RM, Salzman NH, Zahrt TC.) Infect Immun. 2012 Sep;80(9):3018-33 PMID: 22689819 PMCID: PMC3418728 SCOPUS ID: 2-s2.0-84867585909 06/13/2012
Adaptation to environmental stimuli within the host: two-component signal transduction systems of Mycobacterium tuberculosis.

(Bretl DJ, Demetriadou C, Zahrt TC.) Microbiol Mol Biol Rev. 2011 Dec;75(4):566-82 PMID: 22126994 PMCID: PMC3232741 SCOPUS ID: 2-s2.0-84455173453 12/01/2011
Components of the Rv0081-Rv0088 locus, which encodes a predicted formate hydrogenlyase complex, are coregulated by Rv0081, MprA, and DosR in Mycobacterium tuberculosis.

(He H, Bretl DJ, Penoske RM, Anderson DM, Zahrt TC.) J Bacteriol. 2011 Oct;193(19):5105-18 PMID: 21821774 PMCID: PMC3187382 SCOPUS ID: 2-s2.0-80053603928 08/09/2011
The HtrA-like serine protease PepD interacts with and modulates the Mycobacterium tuberculosis 35-kDa antigen outer envelope protein.

(White MJ, Savaryn JP, Bretl DJ, He H, Penoske RM, Terhune SS, Zahrt TC.) PLoS One. 2011 Mar 22;6(3):e18175 PMID: 21445360 PMCID: PMC3062566 SCOPUS ID: 2-s2.0-79952927866 03/30/2011
Identification, characterization and immunogenicity of an O-antigen capsular polysaccharide of Francisella tularensis.

(Apicella MA, Post DM, Fowler AC, Jones BD, Rasmussen JA, Hunt JR, Imagawa S, Choudhury B, Inzana TJ, Maier TM, Frank DW, Zahrt TC, Chaloner K, Jennings MP, McLendon MK, Gibson BW.) PLoS One. 2010 Jul 06;5(7):e11060 PMID: 20625403 PMCID: PMC2897883 SCOPUS ID: 2-s2.0-77955411445 07/14/2010
PepD participates in the mycobacterial stress response mediated through MprAB and SigE.

(White MJ, He H, Penoske RM, Twining SS, Zahrt TC.) J Bacteriol. 2010 Mar;192(6):1498-510 PMID: 20061478 PMCID: PMC2832534 SCOPUS ID: 2-s2.0-77949371118 01/12/2010
Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development.

(Pechous RD, McCarthy TR, Zahrt TC.) Microbiol Mol Biol Rev. 2009 Dec;73(4):684-711 PMID: 19946137 PMCID: PMC2786580 SCOPUS ID: 2-s2.0-71449102798 12/01/2009
A Francisella tularensis Schu S4 purine auxotroph is highly attenuated in mice but offers limited protection against homologous intranasal challenge.

(Pechous RD, McCarthy TR, Mohapatra NP, Soni S, Penoske RM, Salzman NH, Frank DW, Gunn JS, Zahrt TC.) PLoS One. 2008 Jun 25;3(6):e2487 PMID: 18575611 PMCID: PMC2429968 SCOPUS ID: 2-s2.0-49649100202 06/26/2008

Thomas C. Zahrt, PhD