Heme and hemoglobin utilization by Mycobacterium tuberculosis.

Authors

Avishek Mitra, University of Alabama at Birmingham
Ying-Hui Ko, Thomas Jefferson UniversityFollow
Gino Cingolani, Thomas Jefferson University; National Research Council, Via Amendola, ItalyFollow
Michael Niederweis, University of Alabama at Birmingham

Document Type

Article

Publication Date

9-18-2019

Comments

This article is the author’s final published version in Nature Communications, Volume 10, Issue 1, March 2018, Page 4260.

The published version is available at https://doi.org/10.1038/s41467-019-12109-5. Copyright © Mitra et al.

Abstract

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.

Recommended Citation

Mitra, Avishek; Ko, Ying-Hui; Cingolani, Gino; and Niederweis, Michael, "Heme and hemoglobin utilization by Mycobacterium tuberculosis." (2019). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 159.
https://jdc.jefferson.edu/bmpfp/159

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

31534126

Language

English