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 #
5R37AI026170-24
Application #
8223223
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lacourciere, Karen A
Project Start
1988-12-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
24
Fiscal Year
2012
Total Cost
$507,880
Indirect Cost
$201,928

  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:
Glass, Lisa N; Swapna, Ganduri; Chavadi, Sivagami Sundaram et al. (2017) Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth. PLoS Pathog 13:e1006515
Johnson, Alison J; Kennedy, Steven C; Lindestam Arlehamn, Cecilia S et al. (2017) Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+ T Cells. Infect Immun 85:
Saito, Kohta; Warrier, Thulasi; Somersan-Karakaya, Selin et al. (2017) Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations. Proc Natl Acad Sci U S A 114:E4832-E4840
Kerantzas, Christopher A; Jacobs Jr, William R (2017) Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application. MBio 8:
Vilchèze, Catherine; Hartman, Travis; Weinrick, Brian et al. (2017) Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 114:4495-4500

Showing the most recent 10 out of 89 publications