Thomas Christopher Zahrt, PhD
Associate Professor
Microbiology and Molecular Genetics
Medical College of Wisconsin
Research Focus: Bacterial Pathogenesis and Host-Cell Interactions
PhD: University of Illinois, Urbana (1997) Microbiology
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The ability of intracellular bacterial pathogens to sense and successfully respond to various environmental stimuli during an infection is essential for their survival and proliferation within the host. For example, many intracellular pathogens must persist in phagocytic cells of the host to cause disease, a normally hostile environment that is detrimental to the survival of most organisms. Research in my laboratory is focused on characterizing the regulatory mechanisms utilized by intracellular pathogens to establish, maintain, or reactivate from infection in the host. To investigate these mechanisms, my laboratory studies the host-pathogen interactions of Mycobacterium tuberculosis.
Tuberculosis is the leading cause of death in the world from a single infectious agent and is responsible for more than 3 million deaths worldwide annually. The high mortality rate in individuals infected with the causative agent, Mycobacterium tuberculosis, is due in part to the ability of the tubercle bacilli to parasitize alveolar macrophages, and establish long-term persistent infection in the host despite the presence of a cell-mediated immune response. Although the current anti-tubercular drug arsenal is effective in treating individuals suffering from active acute disease, these drugs are ineffective in treating the nearly 2 billion individuals that are latent carriers of M. tuberculosis, or that are infected with multi-drug resistant strains of M. tuberculosis.
Current research efforts in my laboratory are directed at characterizing the role that global regulatory systems play in the pathogenesis of these organisms. In particular, we are focused on those transcriptional regulators that mediate adaptation processes in response to stressful stimuli encountered during infection. The laboratory utilizes a combination of genetic and biochemical approaches to investigate the molecular mechanisms of these systems, as well as tissue culture and animal model systems of infection to investigate the physiological role of these systems in the context of M. tuberculosis pathogenesis. Collectively, the goal of these studies is to develop novel or improved vaccines that are capable of providing enhanced protection against infection with this agent.
Recent Publications
White MJ, Savaryn JP, Bretl DJ, He H, Penoske RM, Terhune SS, Zahrt TC. The HtrA-like serine protease PepD interacts with and modulates the Mycobacterium tuberculosis 35-kDa antigen outer envelope protein. PLoS One. 2011 Mar 22;6(3):e18175.
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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. Identification, Characterization and Immunogenicity of an O-Antigen Capsular Polysaccharide of Francisella tularensis. PLoS One. 2010 Jul 6;5(7):e11060.
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White MJ, He H, Penoske RM, Twining SS, Zahrt TC. PepD participates in the mycobacterial stress response mediated through MprAB and SigE. J Bacteriol. 2010 Mar;192(6):1498-510.
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Pechous RD, McCarthy TR, Zahrt TC. Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development. Microbiol Mol Biol Rev. 2009 Dec;73(4):684-711. Review.
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Pechous RD, McCarthy TR, Mohapatra NP, Soni S, Penoske RM, Salzman NH, Frank DW, Gunn JS, Zahrt TC. A Francisella tularensis Schu S4 purine auxotroph is highly attenuated in mice but offers limited protection against homologous intranasal challenge. PLoS ONE. 2008 Jun 25;3(6):e2487.
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Maier TM, Casey MS, Becker RH, Dorsey CW, Glass EM, Maltsev N, Zahrt TC, Frank DW. Identification of Francisella tularensis Himar1-based transposon mutants defective for replication in macrophages. Infect Immun. 2007 Nov;75(11):5376-89. Epub 2007 Aug 6.
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Frank DW, Zahrt TC. Genetics and genetic manipulation in francisella tularensis. Ann N Y Acad Sci. 2007 Jun;1105:67-97. Epub 2007 Mar 29.
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Pechous R, Celli J, Penoske R, Hayes SF, Frank DW, Zahrt TC. Construction and characterization of an attenuated purine auxotroph in a Francisella tularensis live vaccine strain. Infect Immun. 2006 Aug;74(8):4452-61.
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Maier TM, Pechous R, Casey M, Zahrt TC, Frank DW. In vivo Himar1-based transposon mutagenesis of Francisella tularensis. Appl Environ Microbiol. 2006 Mar;72(3):1878-85.
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He H, Hovey R, Kane J, Singh V, Zahrt TC. MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis. J Bacteriol. 2006 Mar;188(6):2134-43.
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He H, Zahrt TC. Identification and characterization of a regulatory sequence recognized by Mycobacterium tuberculosis persistence regulator MprA. J. Bacteriol. 2005 Jan;187(1):202-212.
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Maier TM, Havig A, Casey M, Nano FE, Frank DW, Zahrt TC. Construction and characterization of a highly efficient francisella shuttle plasmid. Appl Environ Microbiol. 2004 Dec;70(12):7511-9.
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Hessner MJ, Singh VK, Wang X, Khan S, Tschannen MR, Zahrt TC. Utilization of a labeled tracking oligonucleotide for visualization and quality control of spotted 70-mer arrays. BMC Genomics. 2004 Feb 09;5(1):12.
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Zahrt TC, Wozniak C, Jones D, Trevett A. Functional analysis of the Mycobacterium tuberculosis MprAB two-component signal transduction system. Infect Immun. 2003 Dec;71(12):6962-70.
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Zahrt TC. Molecular mechanisms regulating persistent Mycobacterium tuberculosis infection. Microbes Infect. 2003 Feb;5(2):159-67. Review.
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Zahrt TC, Deretic V. Reactive nitrogen and oxygen intermediates and bacterial defenses: unusual adaptations in Mycobacterium tuberculosis. Antioxid Redox Signal. 2002 Feb;4(1):141-59. Review.
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Contact Information
Email: tzahrt@mcw.edu
Phone: 414-955-7429
Room: TBRC C3970