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Cell Host Microbe. 2015 Sep 9;18(3):363-70. doi: 10.1016/j.chom.2015.08.001. Epub 2015 Aug 27.

Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes.

Author information

1
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.
2
Department of Microbiology, New York University School of Medicine, NY 10016, USA.
3
CIRI, Inserm U1111, CNRS UMR 5308, Lyon, France; Université Claude Bernard Lyon-1, Ecole Normale Supérieure, 69007 Lyon, France.
4
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.
5
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
6
Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
7
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.
8
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.
9
Department of Microbiology, New York University School of Medicine, NY 10016, USA. Electronic address: victor.torres@nyumc.org.

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.

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PMID:
26320997
PMCID:
PMC4578157
DOI:
10.1016/j.chom.2015.08.001
[Indexed for MEDLINE]
Free PMC Article

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