title: Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes.
abstract: 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.
authors: 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.
authors: András N
authors: AN
authors: Spaan
authors: Department of Microbiology, New York University School of Medicine, NY 10016, USA.
authors: Tamara
authors: T
authors: Reyes-Robles
authors: CIRI, Inserm U1111, CNRS UMR 5308, Lyon, France; Université Claude Bernard Lyon-1, Ecole Normale Supérieure, 69007 Lyon, France.
authors: Cédric
authors: C
authors: Badiou
authors: Inserm U1134, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France; Institut National de la Transfusion Sanguine, F-75739 Paris, France; Laboratoire d'Excellence GR-Ex, 75238 Paris, France.
authors: Sylvie
authors: S
authors: Cochet
authors: Department of Microbiology, New York University School of Medicine, NY 10016, USA.
authors: Kristina M
authors: KM
authors: Boguslawski
authors: Department of Microbiology, New York University School of Medicine, NY 10016, USA.
authors: Pauline
authors: P
authors: Yoong
authors: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors: Christopher J
authors: CJ
authors: Day
authors: Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors: Carla J C
authors: CJ
authors: de Haas
authors: Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors: Kok P M
authors: KP
authors: van Kessel
authors: CIRI, Inserm U1111, CNRS UMR 5308, Lyon, France; Université Claude Bernard Lyon-1, Ecole Normale Supérieure, 69007 Lyon, France; Hospices Civils de Lyon, 69007 Lyon, France.
authors: François
authors: F
authors: Vandenesch
authors: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors: Michael P
authors: MP
authors: Jennings
authors: Inserm U1134, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France; Institut National de la Transfusion Sanguine, F-75739 Paris, France; Laboratoire d'Excellence GR-Ex, 75238 Paris, France.
authors: Caroline
authors: C
authors: Le Van Kim
authors: Inserm U1134, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France; Institut National de la Transfusion Sanguine, F-75739 Paris, France; Laboratoire d'Excellence GR-Ex, 75238 Paris, France.
authors: Yves
authors: Y
authors: Colin
authors: Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors: Jos A G
authors: JA
authors: van Strijp
authors: CIRI, Inserm U1111, CNRS UMR 5308, Lyon, France; Université Claude Bernard Lyon-1, Ecole Normale Supérieure, 69007 Lyon, France. Electronic address: thomas.henry@inserm.fr.
authors: Thomas
authors: T
authors: Henry
authors: Department of Microbiology, New York University School of Medicine, NY 10016, USA. Electronic address: victor.torres@nyumc.org.
authors: Victor J
authors: VJ
authors: Torres
mesh_terms: D004375:Duffy Blood-Group System / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis; D054884:Host-Pathogen Interactions; D006801:Humans; D007956:Leukocidins / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D007956:Leukocidins; D011956:Receptors, Cell Surface