9bch

Publication Abstract from PubMed

To successfully mount infections, nearly all bacterial pathogens must acquire iron, a key metal cofactor that primarily resides within human hemoglobin. Corynebacterium diphtheriae 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 C. diphtheriae selectively captures iron-loaded hemoglobin by partially ensconcing the heme molecules of its alpha subunits. Quantitative growth and heme release measurements are compatible with C. diphtheriae acquiring heme passively released from hemoglobin's beta subunits. We propose a model in which HbpA and heme-binding receptors collectively function on the C. diphtheriae surface to capture hemoglobin and its spontaneously released heme. Acquisition mechanisms that exploit the propensity of hemoglobin's beta subunit to release heme likely represent a common strategy used by bacterial pathogens to obtain iron during infections.

Molecular basis of hemoglobin binding and heme removal in Corynebacterium diphtheriae.,Mahoney BJ, Lyman LR, Ford J, Soule J, Cheung NA, Goring AK, Ellis-Guardiola K, Collazo MJ, Cascio D, Ton-That H, Schmitt MP, Clubb RT Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2411833122. doi: , 10.1073/pnas.2411833122. Epub 2024 Dec 31. PMID:39739808^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.