Tuberculosis is the leading cause of death in adults due to an infectious organism. By the end of this century there may be as many as 90 million new cases of tuberculosis resulting in up to 30 million deaths. The failure of antimicrobial therapy and the dangerous association between tuberculosis and AIDS have brought renewed interest in studying M. tuberculosis, the organism responsible for this disease. A better understanding of the basic biology of the organism and the development of new anti-mycobacterial drugs are important goals of mycobacterial research. The cell envelope is an outstanding characteristic if the mycobacteria, consisting of a variety of polysaccharides such as arabinogalactan, lipoarabinomannan, and peptidoglycan, along with several different types of lipids including various glycolipids and the mycolic acids. The peptidoglycan layer of the cell envelope serves as the anchor for the principal components of the cell envelope and provides shape and structural integrity to the cell. The long-term goal of this proposal is a deeper understanding of the biosynthesis and assembly of the mycobacterial cell envelope. The specific goal of this proposal is to understand more about the genetics and biosynthesis of the peptidoglycan layer of the envelope.
The specific aims of this proposal are: 1) Determining the significance of N-glycolylation of the mycobacterial peptidoglycan. 2) Investigating the architecture of the peptidoglycan and the role it plays in the organization of the cell envelope. 3) Using beta-lactam antibiotics as tools to probe mycobacterial peptidoglycan biosynthesis. For the aims of this proposal, the Pi will study M. tuberculosis and M. smegmatis as a model organism using the techniques of classical bacterial genetics, molecular biology and biochemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI047311-05
Application #
6747368
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Sizemore, Christine F
Project Start
2000-09-30
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
5
Fiscal Year
2004
Total Cost
$279,125
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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