A Mechanistic Understanding of Tuberculosis Progression Through Bacterial Reporter Strains

Principal Investigator: David Russell

Department of Microbiology and Immunology
Sponsor: NIH-National Institute of Allergy and Infectious Diseases (NIAID)
Grant Number: 5R01AI134183-04
Title: A Mechanistic Understanding of Tuberculosis Progression Through Bacterial Reporter Strains
Project Amount: $707,313
Project Period: July 2020 to June 2021

DESCRIPTION (provided by applicant): 

Due to its extensive penetrance of the human population, Mycobacterium tuberculosis (Mtb) remains a serious health risk to those individuals living with HIV. TB vaccine development programs are hampered by our poor understanding of the immune mechanisms underpinning disease progression. What we propose in this application is the utilization of Mtb reporter strains to provide a functional readout of microbial fitness and replication to enable us to identify and characterize those phagocytes that restrict bacterial growth (controllers) versus those phagocytes the promote bacterial growth (permissive) to understand the basis of disease progression in human tuberculosis. Our hypothesis is that Mtb reporter strains represent a novel route to the identification of the phagocyte populations that best restrict or promote bacterial replication, and that defining these cell populations will provide a rational framework for understanding immune control of tuberculosis.