# Validating cholesterol-mediated Mycobacterium tuberculosis resistance to oxidative stress as a drug target

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $393,766

## Abstract

Project Summary
 One third of the world's population carries the infectious agent Mycobacterium tuberculosis (Mtb) that
causes tuberculosis (TB). Current treatments for TB disease are not straightforward. Drug resistance to TB
drugs results from insufficient treatments that select for resistance, as well as from inherently resistant popula-
tions. Because of the arduous and difficult to follow regimen for TB treatment, there were approximately
480,000 cases of multi-drug resistant TB (MDR-TB) and 100,000 cases of rifampicin-resistant TB (RR-TB) in
2015. Treatment of MDR-TB has a 52% success rate, and about 15% of cases develop into extensively-drug
resistant TB (XDR-TB), which has been found in 117 countries.
 Multi-drug resistant TB requires treatment for two years with a cocktail of at least 5 drugs. New drug with
mechanisms of action that eradicate persistence and drug tolerant populations will reduce treatment times and
the spread of virulent drug resistant strains. We propose that Mtb cholesterol metabolism contributes to persis-
tence in the host and presents a target for therapeutics with new mechanisms of action. Our studies will pro-
vide much needed information about mechanism of oxidative stress resistance in Mtb and how these mecha-
nisms are tied to cholesterol metabolism. Upon completion, (1) we will identify the molecular target of a TB
drug potentiator that has the capacity to shorten TB treatment times. (2) We will characterize the biochemical
function of a regulon that is only encoded in mycobacterial pathogens, and which our preliminary data suggest
contains the target of our potentiators. (3) We will model control of metabolite flow between cholesterol catabo-
lism and ROS resistance pathways. Taken together, these studies will identify vulnerable targets for drug dis-
covery that eliminates Mtb persistence and drug tolerance.

## Key facts

- **NIH application ID:** 9920672
- **Project number:** 5R01AI134054-04
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** NICOLE S SAMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,766
- **Award type:** 5
- **Project period:** 2017-06-19 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920672

## Citation

> US National Institutes of Health, RePORTER application 9920672, Validating cholesterol-mediated Mycobacterium tuberculosis resistance to oxidative stress as a drug target (5R01AI134054-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9920672. Licensed CC0.

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