Abstract

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.

  Funding Agency

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

  Institution

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

  Publications

Vilchèze, Catherine; Copeland, Jacqueline; Keiser, Tracy L et al. (2018) Rational Design of Biosafety Level 2-Approved, Multidrug-Resistant Strains of Mycobacterium tuberculosis through Nutrient Auxotrophy. MBio 9:
Harbut, Michael B; Yang, Baiyuan; Liu, Renhe et al. (2018) Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity. Angew Chem Int Ed Engl 57:3478-3482
Vilchèze, Catherine; Weinrick, Brian; Leung, Lawrence W et al. (2018) Plasticity of Mycobacterium tuberculosis NADH dehydrogenases and their role in virulence. Proc Natl Acad Sci U S A 115:1599-1604
Vilchèze, Catherine; Kim, John; Jacobs Jr, William R (2018) Vitamin C Potentiates the Killing of Mycobacterium tuberculosis by the First-Line Tuberculosis Drugs Isoniazid and Rifampin in Mice. Antimicrob Agents Chemother 62:
Bhatt, Kiranmai; Machado, Henrique; Osório, Nuno S et al. (2018) A Nonribosomal Peptide Synthase Gene Driving Virulence in Mycobacterium tuberculosis. mSphere 3:
Yang, Yong; Thomas, Joseph; Li, Yunlong et al. (2017) Defining a temporal order of genetic requirements for development of mycobacterial biofilms. Mol Microbiol 105:794-809
Qaqish, Arwa; Huang, Dan; Chen, Crystal Y et al. (2017) Adoptive Transfer of Phosphoantigen-Specific ?? T Cell Subset Attenuates Mycobacterium tuberculosis Infection in Nonhuman Primates. J Immunol 198:4753-4763
Stratton, Thomas P; Perryman, Alexander L; Vilchèze, Catherine et al. (2017) Addressing the Metabolic Stability of Antituberculars through Machine Learning. ACS Med Chem Lett 8:1099-1104
Ryan, Ali; Polycarpou, Elena; Lack, Nathan A et al. (2017) Investigation of the mycobacterial enzyme HsaD as a potential novel target for anti-tubercular agents using a fragment-based drug design approach. Br J Pharmacol 174:2209-2224
Hanauer, David I; Graham, Mark J; SEA-PHAGES et al. (2017) An inclusive Research Education Community (iREC): Impact of the SEA-PHAGES program on research outcomes and student learning. Proc Natl Acad Sci U S A 114:13531-13536

Showing the most recent 10 out of 89 publications