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Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes. 2015
András N Spaan, and
Tamara Reyes-Robles, and
Cédric Badiou, and
Sylvie Cochet, and
Kristina M Boguslawski, and
Pauline Yoong, and
Christopher J Day, and
Carla J C de Haas, and
Kok P M van Kessel, and
François Vandenesch, and
Michael P Jennings, and
Caroline Le Van Kim, and
Yves Colin, and
Jos A G van Strijp, and
Thomas Henry, and
Victor J Torres
CIRI, Inserm U1111, CNRS UMR 5308, Lyon, France; Université Claude Bernard Lyon-1, Ecole Normale Supérieure, 69007 Lyon, France; Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
In order for Staphylococcus aureus to thrive inside the mammalian host, the bacterium has to overcome iron scarcity. S. aureus is thought to produce toxins that lyse erythrocytes, releasing hemoglobin, the most abundant iron source in mammals. Here we identify the Duffy antigen receptor for chemokines (DARC) as the receptor for the S. aureus hemolytic leukocidins LukED and HlgAB. By assessing human erythrocytes with DARC polymorphisms, we determined that HlgAB- and LukED-mediated lysis directly relates to DARC expression. DARC is required for S. aureus-mediated lysis of human erythrocytes, and DARC overexpression is sufficient to render cells susceptible to toxin-mediated lysis. HlgA and LukE bind directly to DARC through different regions, and by targeting DARC, HlgAB and LukED support S. aureus growth in a hemoglobin-acquisition-dependent manner. These findings elucidate how S. aureus targets and lyses erythrocytes to release one of the scarcest nutrients within the mammalian host.
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