# Nutrient Uptake during Anthrax Disease

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $396,250

## Abstract

Project Summary
Pathogenic bacteria need to acquire essential nutrients to establish and sustain an infection in their
hosts. The host restricts access to such nutrients, a concept termed nutritional immunity. As such,
bacterial nutrient import systems, and the metabolic regulators that govern them, represent next-
generation targets for novel antimicrobials. The Gram-positive bacterium B. anthracis is the causative
agent of anthrax disease and a weapon of bioterrorism. This pathogen has a remarkable ability to
replicate in vertebrates, a virtue that is useful for the study of how bacteria overcome nutritional
immunity. It is well known that the
penultimate step in the biosynthesis of branched amino acids, which
are necessary for all life, requires an enzyme whose activity is dependent on an iron-sulfur cluster.
Our
published work and preliminary data suggests that B. anthracis and related species employ a clever
metabolic mechanism to govern the balance between the intake of branched amino acids and the
maintenance of iron homeostasis in complex host environments. Working under the premise that
bacillus is auxotrophic for valine when external iron levels are low, and thus cannot make branched
amino acids, we hypothesize that host valine liberated from blood proteins stimulates iron acquisition
via the global regulator of virulence in Gram-positive bacteria, CodY. This in turn promotes the import
of iron, thereby relieving the auxotrophy and fueling rapid replication in host blood and tissues. In Aim
1 of this project, we report the discovery of a novel branched amino acid transporter and characterize
its role in the CodY-dependent stimulation of heme-iron acquisition. In Aim 2, we investigate the
mechanism of iron release from heme via two newly uncovered heme-binding enzymes in bacillus.
Finally, in Aim 3, we integrate key aspects of the central model to determine the importance of these
systems in every step of a developing bacillus infection during anthrax disease. Since this network of
nutrient uptake systems and regulators also have homologs in several clinically significant species, the
work here will provide fundamental knowledge of how pathogenic bacteria fuel their metabolism during
virulence.

## Key facts

- **NIH application ID:** 10053299
- **Project number:** 5R01AI097167-08
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ANTHONY W MARESSO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2012-06-21 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053299

## Citation

> US National Institutes of Health, RePORTER application 10053299, Nutrient Uptake during Anthrax Disease (5R01AI097167-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053299. Licensed CC0.

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