# Ironing out mycobacterial persistence: Iron access and utilization in chronic mycobacterial infection

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $48,353

## Abstract

PROJECT SUMMARY/ABSTRACT
Tuberculosis disease, caused by the bacterium Mycobacterium tuberculosis (Mtb) is the leading cause of death
from a single infectious disease worldwide. Mtb requires iron in order to perform essential biochemical reactions
and for the maintenance of redox balance to survive and persist within host cells. During infection, the host
encloses Mtb within the macrophage phagosome and actively restricts bacterial access to iron, resulting in Mtb
contained within iron-deficient lung lesions. We hypothesize that Mtb confronts an iron-restricted environment
as infection persists and requires accessory iron-acquisition molecules to survive inside the host. To test this
hypothesis, a low iron-inducible recombination-based reporter system has been developed in mycobacteria,
which provides a unique tool to identify iron-starved mycobacteria both in vitro and in vivo. This proposal seeks
to i) develop a genetic method to characterize the iron status of mycobacteria, ii) probe the iron available in
differentially activated macrophage environments and iii) assay mycobacterial genes required for iron acquisition
and utilization in vivo. These aims will employ phenotypically-relevant models of Mtb infection, including
macrophage and mouse models of disease. This proposal will also develop a novel technology to probe the
mycobacterial genome, as we will generate a library of transposon mutants in the background of the Mtb reporter
strain such that recombined bacteria will reflect mutations in genes required to access or utilize iron. These
recombined bacteria will be sequenced directly from the inserted transposon to identify the gene of interest.
Therefore, successful completion of this proposal will advance the field by providing new insight into the
mechanisms by which the host restricts iron availability during chronic infection and the mycobacterial genetic
requirements to survive iron depletion in vivo. This proposal will develop cutting-edge technologic approaches
to interrogate the mycobacterial genome in vivo, which can be used to identify new bacterial vulnerabilities and
avenues for treatment.

## Key facts

- **NIH application ID:** 10068378
- **Project number:** 1F30HL151085-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Alexandra Haley Miller
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $48,353
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068378

## Citation

> US National Institutes of Health, RePORTER application 10068378, Ironing out mycobacterial persistence: Iron access and utilization in chronic mycobacterial infection (1F30HL151085-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10068378. Licensed CC0.

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