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

András N Spaan1, Tamara Reyes-Robles2, Cédric Badiou3

  • 1CIRI, 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.

Cell Host & Microbe
|September 1, 2015
PubMed

Insights

Staphylococcus aureus uses the Duffy antigen receptor for chemokines (DARC) to lyse erythrocytes and acquire iron. Targeting DARC helps the bacteria overcome iron scarcity within the host.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Staphylococcus aureus requires iron to thrive in mammalian hosts.
  • The bacterium is thought to lyse erythrocytes to access hemoglobin-rich iron.
  • Hemolytic leukocidins are key virulence factors for S. aureus.

Purpose of the Study:

  • To identify the receptor for Staphylococcus aureus hemolytic leukocidins LukED and HlgAB.
  • To elucidate the role of this receptor in erythrocyte lysis and bacterial iron acquisition.

Main Methods:

  • Identification of the Duffy antigen receptor for chemokines (DARC) as the receptor for LukED and HlgAB.
  • Assessment of human erythrocytes with DARC polymorphisms to correlate lysis with DARC expression.
  • Analysis of HlgA and LukE binding to DARC.

Main Results:

  • DARC is the receptor for S. aureus leukocidins LukED and HlgAB.
  • Erythrocyte lysis mediated by HlgAB and LukED is directly dependent on DARC expression.
  • DARC overexpression renders erythrocytes susceptible to toxin-mediated lysis.
  • HlgAB and LukED target DARC to support S. aureus growth via hemoglobin acquisition.

Conclusions:

  • Staphylococcus aureus utilizes DARC as a receptor for leukocidins to lyse erythrocytes.
  • This mechanism facilitates iron acquisition, crucial for bacterial survival in the host.
  • Targeting DARC is a key strategy for S. aureus to overcome iron scarcity.

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