Tuberculosis (TB) chemotherapy often fails to sterilize Mycobacterium tuberculosis (Mtb) resulting in individuals at risk of relapse TB. The mechanisms that allow Mtb to survive during paucibacillary persistent TB infections are for the most part unknown. Drug treatment and silencing of in vivo essential genes can cure acute and chronic Mtb infections in mice to the extent that CFU can no longer be detected on agar plates. However, as in humans, Mtb in these mice is often not sterilized and paucibacillary persistence eventually results in relapse of TB. We propose to develop a new animal model of paucibacillary persistence and use this model to identify the processes that Mtb requires to persist following apparent eradication. The proposed experiments will increase understanding of the mechanisms leading to paucibacillary persistence and will establish a model for studying paucibacillary disease and relapse in mice.

Public Health Relevance

Tuberculosis (TB) is the world's second leading cause of premature human death from an infectious disease. Work outlined in this proposal will increase our understanding of the mechanisms leading to paucibacillary persistence of M. tuberculosis and has the potential to contribute to the development of new TB drugs, and ultimately help reducing the impact of this disease on global health.

Agency
National Institute of Health (NIH)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI111143-01
Application #
8726604
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065