Molecular basis of hemoglobin binding and heme removal in <i>Corynebacterium diphtheriae</i>
To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. <i>Corynebacterium diphtheriae</i> causes the life-threatening respiratory disease diphtheria and captures hemoglobin for iron scavenging using the surface-displayed receptor HbpA. Here, we show using X-ray crystallography, NMR, and in situ binding measurements that <i>C. diphtheriae</i> selectively captures iron-loaded hemoglobin by partially ensconcing the heme molecules of its α subunits. Quantitative growth and heme release measurements are compatible with <i>C. diphtheriae</i> acquiring heme passively released from hemoglobin's β subunits. We propose a model in which HbpA and heme-binding receptors collectively function on the <i>C. diphtheriae</i> surface to capture hemoglobin and its spontaneously released heme. Acquisition mechanisms that exploit the propensity of hemoglobin's β subunit to release heme likely represent a common strategy used by bacterial pathogens to obtain iron during infections.
Authors
- Robert Clubb (ORCID: https://orcid.org/0000-0001-5718-3985)
- Duilio Cascio (ORCID: https://orcid.org/0000-0001-8285-754X)
- Michael Collazo
- Jordan Ford (ORCID: https://orcid.org/0000-0001-9501-551X)
- Lindsey R. Lyman
- Jess Soule (ORCID: https://orcid.org/0000-0002-6159-4354)
- Nicole A. Cheung
- Andrew K. Goring (ORCID: https://orcid.org/0000-0003-4220-6472)
- Hung Ton‐That (ORCID: https://orcid.org/0000-0003-1611-0469)
- Brendan J. Mahoney (ORCID: https://orcid.org/0000-0003-4323-9276)
- Ken Ellis‐Guardiola (ORCID: https://orcid.org/0000-0001-7966-1052)
- Michael P. Schmitt (ORCID: https://orcid.org/0000-0002-1516-7925)
Institutions
- Center for Biologics Evaluation and Research (US)
- United States Department of Energy (US)
- University of California, Los Angeles (US)
- Food and Drug Administration (TH)
- University of California, Berkeley (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-12-31
- DOI
- https://doi.org/10.1073/pnas.2411833122
- Citations
- 4
- Primary Topic
- Clostridium difficile and Clostridium perfringens research
- Type
- article
- Field-Weighted Citation Impact
- 1.56
Funders
- U.S. Department of Energy
- National Institutes of Health
- Office of Science
- University of California, Los Angeles
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Dental and Craniofacial Research
- Argonne National Laboratory