Mycobacterium tuberculosis, the causative agent of human tuberculosis infects approximately one-third of the world's population and kills nearly two million people each year. New strategies of the treatment of existing disease and improved vaccination methods to prevent new infections will require a greater understanding of the mechanisms used by this pathogen to persist in the host and cause disease. Unlike many other bacterial pathogens, M. tuberculosis interacts with the host largely through the secretion of a wide variety of complex small molecules. Using a new genetic methodology, we have identified secondary metabolite biosynthetic pathways and large multisubunit transport systems that function in concert to promote bacterial growth in vivo and disease progression. Using a panel of M. tuberculosis mutants that lack either transport systems of biosynthetic genes, we will identify the novel compounds that mediate interactions between the bacterium and host (Aim 1). By characterizing the altered interaction between these mutants and the host macrophage, we will determine the the specific roles played by these systems during infection (Aim 2), Finally, we will dissect the structure and functions of individual transporter components to identify virulence-specific adaptations that explain some of the unique biology of this infection (Aim 3).

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Bacterial Pathogenesis Study Section (BACP)
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Jacobs, Gail G
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University of Massachusetts Medical School Worcester
Schools of Medicine
United States
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Prigozhin, Daniil M; Papavinasasundaram, Kadamba G; Baer, Christina E et al. (2016) Structural and Genetic Analyses of the Mycobacterium tuberculosis Protein Kinase B Sensor Domain Identify a Potential Ligand-binding Site. J Biol Chem 291:22961-22969
Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C (2016) Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection. Curr Opin Microbiol 29:30-6
Olive, Andrew J; Sassetti, Christopher M (2016) Metabolic crosstalk between host and pathogen: sensing, adapting and competing. Nat Rev Microbiol 14:221-34
Long, Jarukit E; DeJesus, Michael; Ward, Doyle et al. (2015) Identifying essential genes in Mycobacterium tuberculosis by global phenotypic profiling. Methods Mol Biol 1279:79-95
Murphy, Kenan C; Papavinasasundaram, Kadamba; Sassetti, Christopher M (2015) Mycobacterial recombineering. Methods Mol Biol 1285:177-99
Baer, Christina E; Rubin, Eric J; Sassetti, Christopher M (2015) New insights into TB physiology suggest untapped therapeutic opportunities. Immunol Rev 264:327-43
Feltcher, Meghan E; Gunawardena, Harsha P; Zulauf, Katelyn E et al. (2015) Label-free Quantitative Proteomics Reveals a Role for the Mycobacterium tuberculosis SecA2 Pathway in Exporting Solute Binding Proteins and Mce Transporters to the Cell Wall. Mol Cell Proteomics 14:1501-16
Nambi, Subhalaxmi; Long, Jarukit E; Mishra, Bibhuti B et al. (2015) The Oxidative Stress Network of Mycobacterium tuberculosis Reveals Coordination between Radical Detoxification Systems. Cell Host Microbe 17:829-37
Raimunda, Daniel; Long, Jarukit E; Padilla-Benavides, Teresita et al. (2014) Differential roles for the Co(2+) /Ni(2+) transporting ATPases, CtpD and CtpJ, in Mycobacterium tuberculosis virulence. Mol Microbiol 91:185-97
Shell, Scarlet S; Prestwich, Erin G; Baek, Seung-Hun et al. (2013) DNA methylation impacts gene expression and ensures hypoxic survival of Mycobacterium tuberculosis. PLoS Pathog 9:e1003419

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