Heme and hemoglobin utilization by Mycobacterium tuberculosis
Open accessAbstract
Iron is essential for growth of Mycobacterium tuberculosis (Mtb), but most iron in the human body is stored in heme within hemoglobin. Here, we demonstrate that the substrate-binding protein DppA of the inner membrane Dpp transporter is required for heme and hemoglobin utilization by Mtb. The 1.27 Å crystal structure of DppA shows a tetrapeptide bound in the protein core and a large solvent-exposed crevice for heme binding. Mutation of arginine 179 in this cleft eliminates heme binding to DppA and prevents heme utilization by Mtb. The outer membrane proteins PPE36 and PPE62 are also required for heme and hemoglobin utilization, indicating that these pathways converge at the cell surface of Mtb. Albumin, the most abundant blood protein, binds heme specifically and bypasses the requirements for PPE36, PPE62 and Dpp. Thus, our study reveals albumin-dependent and -independent heme uptake pathways, highlighting the importance of iron acquisition from heme for Mtb.
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M. tuberculosis mechanisms for iron uptake include a heme transporter and two classes of siderophores, mycobactins and carboxymycobactins.
“Its mechanisms for iron uptake include a heme transporter and two classes of siderophores, mycobactins and carboxymycobactins (Mitra et al., 2019;Wells et al., 2013).”
From Iron in infection and immunity (2020) · cites this paper as Mitra et al., 2019
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- Authors
- Mitra, A., Ko, Y.-H., Cingolani, G., & Niederweis, M.
- Affiliations
- University of Alabama at Birmingham (US)
- Thomas Jefferson University (US)
- Corresponding author
- Cingolani, Gino
- Niederweis, Michael
- Venue
- Nature Communications
- Published
- 2019-09-18
- Volume
- 10
- Issue
- 1
- Pages
- 4260-4260
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6751184
- OpenAlex
- W2973853581
- Cited by
- 81
- References
- 76
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 7 · 2022: 16 · 2021: 14 · 2020: 8
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SHAREOK (University of Oklahoma; Oklahoma State University; Central Oklahoma University) (publishedVersion, other-oa)
- The Medicine Forum (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- SHAREOK (University of Oklahoma; Oklahoma State University; Central Oklahoma University) (submittedVersion, other-oa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (P30 CA56036, S10 OD017987)
- University of Alabama at Birmingham
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01AI137338)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- Mycobacterium tuberculosis, heme uptake, hemoglobin utilization, DPPA, substrate-binding protein, outer membrane proteins, albumin, iron acquisition, heme binding, crystal structure
- MeSH terms
- Albumins, Antigens, Bacterial, Bacterial Proteins, Heme, Hemoglobins, Humans, Iron, Mycobacterium tuberculosis, Protein Binding, Protein Structure, Secondary, Crystallography, X-Ray, Periplasmic Binding Proteins
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