# The role of immunity in shaping Mycobacterium tuberculosis metabolism

> **NIH NIH F32** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $68,562

## Abstract

Project Summary
Mycobacterium tuberculosis (Mtb) is the leading cause of death by infectious disease, with two million
deaths annually. For Mtb to thrive within the host, the bacterium must obtain nutrients, including carbon
sources which are essential for growth. Mtb can use four primary carbon sources to meet its needs for
carbon utilization. Mtb primarily resides within the phagosome of host macrophages and must acquire
carbon sources from the macrophage while in this niche. While in this compartment, Mtb also
experiences a wide variety of stresses including reactive nitrogen species (RNS) stress. Previous work
has shown that in vitro exposure of Mtb to nitric oxide (NO) leads to the nitrosylation of proteins that
are essential for glycolysis. Additional preliminary data from our lab shows that either exposing Mtb
transposon libraries to NO in vitro leads to an increased importance of fatty acid degradation and
decreased reliance on glycolytic pathways during NO exposure. This has led us to hypothesize that
exposure to RNS stress leads to changes in the use of carbon by Mtb. To begin to identify how RNS
stress effects carbon utilization, Aim 1 will utilize a library of strains that are unable to either utilize or
acquire each of the carbon sources. This library will be grown in the presence of single carbon sources
and RNS, and growth of each strain will be monitored to determine how the RNS stress affects the
ability of each mutant to grow on each carbon source. In Aim 2, this library will be used to infect
macrophages and mice that are either wildtype or lack the ability to induce NO expression. These
studies will allow us to determine how actual infection conditions affect the ability of Mtb to use various
carbon sources. Finally, Aim 3 will focus on identifying the mechanisms by which RNS stress leads to
changes in carbon usage by Mtb. These studies will provide important data on how Mtb utilizes carbon
under stress conditions and the mechanisms which allow for changes in carbon utilization in vivo.

## Key facts

- **NIH application ID:** 10201465
- **Project number:** 5F32AI147508-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Lisa J. Lojek
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201465

## Citation

> US National Institutes of Health, RePORTER application 10201465, The role of immunity in shaping Mycobacterium tuberculosis metabolism (5F32AI147508-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201465. Licensed CC0.

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