# M. tuberculosis carbon metabolism during infection

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $939,332

## Abstract

The development of TB drugs benefits greatly from validation of novel drug targets in predictive animal models.
M. tuberculosis (Mtb) enzymes in central carbon metabolism are emerging as promising targets for drug
development but have not been validated in animal models that recapitulate the diverse and heterogeneous
environments Mtb encounters in humans. We propose to test the hypothesis that these heterogeneous
environments result in airway, lung and granuloma-dependent nutritional restrictions that, at times, make Mtb
dependent on both glycolysis and gluconeogenesis to establish and maintain infection in nonhuman primates
and/or during paucibacillary infection in mice. We will infect NHPs with Mtb mutants of two enzymes – PFK and
PEPCK - that are required for glycolysis or gluconeogenesis, respectively. We will use deletion mutants to
determine whether these enzymes are required for establishment of infection and use conditional knockdown
mutants to investigate the enzymes importance for growth and survival in different pathologies and for
progression of disease. We will furthermore evaluate these mutants in a relapse mouse model to test the
hypothesis that the nutritional requirements during long-term persistence in mice, when the bacteria cannot be
cultured in vitro, are different from those encountered during active growth and high titer chronic infection and
ask whether they mimic environments encountered in NHPs. This proposal builds on the experience of the multi-
PI team in mycobacterial genetics, metabolism, and animal models, with the goal to dissect the carbon source
requirements for Mtb in the model system that is most similar to human Mtb infection and disease.

## Key facts

- **NIH application ID:** 10854945
- **Project number:** 5R01AI177560-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** SABINE EHRT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $939,332
- **Award type:** 5
- **Project period:** 2023-06-02 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854945

## Citation

> US National Institutes of Health, RePORTER application 10854945, M. tuberculosis carbon metabolism during infection (5R01AI177560-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10854945. Licensed CC0.

---

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