Molecular basis of hemoglobin binding and heme removal in <i>Corynebacterium diphtheriae</i>.

Abstract

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.