This proposal addresses an important element of the current tuberculosis global epidemic, namely the fact, recently stated in a document released by the NIAID, that we know next to nothing about the newly emerging clinical isolates of M. tuberculosis, many of which are W-Beijing strains. We will test the simple hypothesis here that such strains associated with high rates of transmission are simply more virulent than low transmission strains, with a secondary hypothesis being that the more virulent strains escape acquired immunity by generating regulatory T cells. These simple studies will provide important basic information about the relationship between transmissibility and virulence, and are doable within the context of an R21 application.

Public Health Relevance

As an important NIAID document recently noted, we know almost nothing about the newly emerging clinical strains of tuberculosis, many of which are fall under the W-Beijing family. In this proposed study we will measure the virulence of a panel of Beijing isolates associated with a series of outbreaks in the San Francisco area. We will test the simple hypothesis that strains associated with high "transmissibility" are of higher virulence in the relevant guinea pig model compared to others that are not readily transmitted.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI092002-01A1
Application #
8234900
Study Section
Special Emphasis Panel (ZRG1-IDM-R (02))
Program Officer
Parker, Tina M
Project Start
2012-02-15
Project End
2014-01-31
Budget Start
2012-02-15
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$185,365
Indirect Cost
$60,365
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Shanley, Crystal A; Ireton, Gregory C; Baldwin, Susan L et al. (2014) Therapeutic vaccination against relevant high virulence clinical isolates of Mycobacterium tuberculosis. Tuberculosis (Edinb) 94:140-7