Mycobacterim tuberculosis infects approximately2 billion people, of whom greater than 2 million will die each year of tuberculosis.With the emergence of multidrug resistant strains and the growingHIV epidemic, the global problemof tuberculosisis worsening.In the last several years the role of the innate arm of the immune response in the control of M. tuberculosis infection has become apparent. Although this response is often adequatefor long term containmentof the bacilli in healthy individuals, it is insufficient for clearance of the infection. Our recent efforts, indicatethat M. tuberculosis possesses specific mechanismsfor the subversionof immune effector populations.Through understanding these immune evasionmechanisms we will be able to design and develop more effective tuberculosisvaccines. To do so, we will utilizecutting edge high-throughput technology to develop a full array M. tuberculosis deletion library. This invaluable tool will enable the elucidationof the molecular basis for this immune evasion, part of which we have found is mediated by a large gene cluster conserved within pathogenic Mycobacterial species.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI026170-25
Application #
8437272
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lacourciere, Karen A
Project Start
1988-12-01
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
25
Fiscal Year
2013
Total Cost
$477,409
Indirect Cost
$189,813
Name
Albert Einstein College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Panas, Michael W; Jain, Paras; Yang, Hui et al. (2014) Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids. Proc Natl Acad Sci U S A 111:13264-71
Jain, Paras; Hsu, Tsungda; Arai, Masayoshi et al. (2014) Specialized transduction designed for precise high-throughput unmarked deletions in Mycobacterium tuberculosis. MBio 5:e01245-14
Vilchèze, Catherine; Molle, Virginie; Carrère-Kremer, Séverine et al. (2014) Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis. PLoS Pathog 10:e1004115
Cortesia, Claudia; Vilchèze, Catherine; Bernut, Audrey et al. (2014) Acetic Acid, the active component of vinegar, is an effective tuberculocidal disinfectant. MBio 5:e00013-14
Panas, Michael W; Sixsmith, Jaimie D; White, KeriAnn et al. (2014) Gene deletions in Mycobacterium bovis BCG stimulate increased CD8+ T cell responses. Infect Immun 82:5317-26
Berney, Michael; Greening, Chris; Conrad, Ralf et al. (2014) An obligately aerobic soil bacterium activates fermentative hydrogen production to survive reductive stress during hypoxia. Proc Natl Acad Sci U S A 111:11479-84
Sixsmith, Jaimie D; Panas, Michael W; Lee, Sunhee et al. (2014) Recombinant Mycobacterium bovis bacillus Calmette-Guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques. Clin Vaccine Immunol 21:1385-95
Pecsi, Ildiko; Hards, Kiel; Ekanayaka, Nandula et al. (2014) Essentiality of succinate dehydrogenase in Mycobacterium smegmatis and its role in the generation of the membrane potential under hypoxia. MBio 5:
Stec, Jozef; Vilchèze, Catherine; Lun, Shichun et al. (2014) Biological evaluation of potent triclosan-derived inhibitors of the enoyl-acyl carrier protein reductase InhA in drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis. ChemMedChem 9:2528-37
Pope, Welkin H; Jacobs-Sera, Deborah; Russell, Daniel A et al. (2014) Genomics and proteomics of mycobacteriophage patience, an accidental tourist in the Mycobacterium neighborhood. MBio 5:e02145

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