# Biomarkers of PZA activity and it's target populations

> **NIH NIH U19** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $449,300

## Abstract

Pyrazinamide (PZA) is a cornerstone of modern TB chemotherapy due to its unique ability to shorten the 
duration of nearly all clinically used regimens. However, resistance is emerging while prospects for a 
replacement remain lacking, threatening the duration of all future chemotherapies. 
Understanding the molecular basis for the unique activity of PZA will allow development of additional 
regimen shortening agents that target the same pathways. However, efforts to develop a functional 
replacement for PZA remain hindered by fundamental gaps in our understanding of its microbiologic and 
biochemical targets. 
Here, we propose to overcome these gaps by identifying physiologic biomarkers of PZA activity and 
susceptibility. These studies will specifically integrate experimental studies of PZA in vitro activity with in 
vivo studies of PZA activity as reported by the transcriptional profiles of Mtb recovered from the lungs of 
infected mice or sputa of culture confirmed patients. Based on our preliminary data, these studies will also 
test the specific hypothesis that PZA targets Mtb subpopulations whose viability is strictly dependent on NAD 
salvage pathway activity. By integrating parallel in vitro and in vivo studies with hypothesis-based and 
unbiased approaches, this project will provide deeper insights into the target(s) and/or mechanism(s)-of-action 
of PZA, the specific microbiologic subpopulations it targets, and a molecular signature of its activity 
that can be used to facilitate the development of new agents targeting the same pathways as PZA.

## Key facts

- **NIH application ID:** 9970382
- **Project number:** 5U19AI111143-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Michael S Glickman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,300
- **Award type:** 5
- **Project period:** 2014-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970382

## Citation

> US National Institutes of Health, RePORTER application 9970382, Biomarkers of PZA activity and it's target populations (5U19AI111143-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9970382. Licensed CC0.

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