Nearly one-third of the world population is infected with Mycobacterium tuberculosis. This reservoir contributes towards an increasing incidence of tuberculosis, with about 11 million new cases and 1.8 million deaths every year. The emergence of multi-drug resistant strains combined with low diagnostic and therapeutic coverage in many developing countries, has worsened the disease burden caused by TB. The profound success of Mycobacterium tuberculosis in causing disease depends on its ability to successfully utilize the host?s cellular machineries including the lipid biosynthesis pathway to subvert the immune system. Our understanding of these processes especially that of the host lipid biology in the context of Mycobacterium tuberculosis infection is limited.
The aim of the proposed work is to study the role of host?s lipid biosynthesis in the entry, replication and killing of Mycobacterium tuberculosis. For this purpose, individual knockout macrophage cell lines that lack genes involved in the biosynthesis of lipids will be generated using CRISPR/Cas9-technology. Understanding these pathways or processes essential for the life cycle of Mycobacterium tuberculosis is crucial, as they represent potential targets for new therapeutics.

Public Health Relevance

According to the World Health Organization estimates, one third of the world?s population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. The profound success of this pathogen in causing disease is due to its inherent ability to successfully utilize the host?s cellular lipid biosynthetic pathways to subvert the immune system. We will therefore aim to identify and characterize the host lipid factors that are used by Mycobacterium to invade, persist, and propagate the host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI124225-02
Application #
9397521
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kraigsley, Alison
Project Start
2016-12-15
Project End
2018-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239