# Investigation of the mechanisms and effects of riboregulation of iron homeostasis in M. tuberculosis

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $234,875

## Abstract

Summary
Tuberculosis (TB) is a significant public health problem worldwide. Although the number of deaths
due to TB has decreased in recent years thanks to improved diagnostics and early treatment, the
sustained increase in antibiotic resistance and the shortage of new effective drugs against
Mycobacterium tuberculosis threatens to undermine TB control efforts. Our studies focus on
exploiting M. tuberculosis (Mtb) sensitivity to iron dysregulation to generate new therapeutic
strategies that prevent Mtb virulence and potentiate antibiotic action.
Iron is an essential micronutrient required by M. tuberculosis to establish a productive infection.
However, excess iron can be very toxic due to the propensity of this metal to catalyze the
production of reactive oxygen species, which can damage all macromolecules. Like all iron-
dependent cells, Mtb must balance intracellular iron levels as it encounters diverse iron
environments in the host. Evidence from animal studies indicates that the ability to maintain iron
homeostasis is essential for Mtb to proliferate and cause disease. In turn, our previous studies
established that Mtb depends on the global transcriptional regulator, IdeR, to control iron
homeostasis.
Our preliminary studies characterized a natural antisense transcript (IdeR-AS) capable of inducing
iron dysregulation when expressed in trans in Mtb. Although this RNA alters the expression of
genes controlled by IdeR, it does not seem to act by altering IdeR levels, and its mode of action
is not understood. We hypothesize that IdeR-AS modulates IdeR activity. Our goals for this
proposal are to investigate IdeR-AS mode of action and evaluate the synergy between IdeR-AS
and antibiotics. We expect that deciphering how this RNA influences iron regulation would guide
efforts to target iron homeostasis in Mtb.

## Key facts

- **NIH application ID:** 10190035
- **Project number:** 1R21AI159055-01
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Gloria Marcela Rodriguez
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,875
- **Award type:** 1
- **Project period:** 2021-02-04 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190035

## Citation

> US National Institutes of Health, RePORTER application 10190035, Investigation of the mechanisms and effects of riboregulation of iron homeostasis in M. tuberculosis (1R21AI159055-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190035. Licensed CC0.

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