# The impact of pyrazinamide on metabolism in Mycobacterium tuberculosis.

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $385,000

## Abstract

   
DESCRIPTION (provided by applicant):  Each year, Mycobacterium tuberculosis infections contribute to over 8 million new cases of tuberculosis (TB) and nearly 2 million deaths. Pyrazinamide (PZA) is a first-line sterilizing anti-tubercular drug that is anticipated to be an irreplaceable component of future TB treatment regimens. Despite more than 60 years of clinical use of PZA, the mechanistic basis for its activity has yet to be resolved. Previous studie have demonstrated that PZA is a pro-drug that is converted to the active form of pyrazinoic acid (POA) by the M. tuberculosis amidase PncA, and that loss of function mutations in pncA account for the vast majority of PZA resistance. In addition, while PZA is only conditionally bacteriostatic for M. tuberculosis in laboratory culture, this drug mediates sterilization of bacili in humans and in animal models of infection. Thus, there is an as yet undefined host-dependent activity involved in potentiation of PZA action on M. tuberculosis. Our long-term goal for this project is to define the mechanistic basis for PZA action against M. tuberculosis. It is known that
POA, but not PZA, forms complexes with several divalent metals involved in biocatalysis and oxidative stress, yet the relevance of this interaction for PZA action has not been explored. We are using a multidisciplinary approach to address the hypothesis that PZA treatment has a profound impact on metal homeostasis and oxidative stress in M. tuberculosis. These studies will shed new light on the poorly understood mode of action of PZA and stand to explain the dichotomous outcome of M. tuberculosis PZA exposure in culture versus in a mammalian system. Resolving the basis for PZA action will guide the discovery of novel agents with a conserved or improved action against M. tuberculosis to counter drug resistance.

## Key facts

- **NIH application ID:** 9849162
- **Project number:** 5R01AI123146-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** ANTHONY D BAUGHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2016-02-01 → 2021-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849162

## Citation

> US National Institutes of Health, RePORTER application 9849162, The impact of pyrazinamide on metabolism in Mycobacterium tuberculosis. (5R01AI123146-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849162. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*