# NIH grant: Discovery and preliminary characterization of proteins required for Mycobacterium tuberculosis heme degradation (1R21AI193989-01A1) — retained record

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[original source ↗](https://reporter.nih.gov/project-details/1R21AI193989-01A1)

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NIH grant 1R21AI193989-01A1: Discovery and preliminary characterization of proteins required for Mycobacterium tuberculosis heme degradation
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Celia  Goulding. Award: $205216.
Start: 2026-07-03T00:00:00.
Tuberculosis (TB) continues to kill millions of people around the world, and the
pathogenic bacteria Mycobacterium tuberculosis (Mtb) is the causative agent of TB.
New tools to prevent and treat this deadly disease are urgently needed. Iron is an
essential metal for all forms of life and most bacterial pathogens including Mtb must
import iron from its host to survive. Therefore, Mtb iron uptake pathways and their
regulation may provide good targets for therapeutic development. We will describe the
further characterization of a protein in the Mtb heme uptake pathway that catalyzes the
release of iron from heme.
 This proposal aims to discover the additional required proteins in Mtb heme
catabolism. The final step in the Mtb heme acquisition pathway is cytosolic heme
degradation by the IsdG-type protein, MhuD. Canonical human heme oxygenases (HOs)
are distinct both in sequence and structure from IsdG-type proteins. Unlike HOs, there is
still a knowledge gap in the fate of the IsdG-type protein tetrapyrrole products. The high
affinity of IsdG-type proteins for their tetrapyrrole products suggests that there is an
additional protein in the heme uptake network that is responsible for product extraction
from IsdG-type proteins. We propose that like HOs, the protein that extracts and reduces
the MhuD product is one of the putative Mtb biliverdin reductases (BVRs), which are also
sequence and structure distinct from human BVRs. Another unknown protein involved in
MhuD heme degradation is the protein that provides the electron source to facilitate the
reaction. We aim to identify these proteins of interest by discovery-based techniques.
 Utilizing biochemical and microbiology techniques, this proposal will investigate
the fate of MhuD tetrapyrrole products and discover the protein that provides electrons
for MhuD heme degradation. The results of this study will (1) lay the groundwork to
further explore the downstream steps for MhuD heme degradation, and (2) identify
unique Mtb targets for therapeutic development.
```



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