ArticleCell host & microbe2019
Staphylococcus aureus Leukocidins Target Endothelial DARC to Cause Lethality in Mice.
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Article in Cell host & microbe, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 39 citations in OpenAlex.
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Authors and funding
31 authors at 6 institutions in 2 countries.
Ashira LubkinDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Warren L LeeKeenan Research Centre, St Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. Electronic address: leew@smh.ca.
Francis AlonzoDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Changsen WangKeenan Research Centre, St Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
Jason AligoJanssen Research & Development LLC, 1400 McKean Road, Spring House, PA 19477, USA.
Matthew KellerDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Natasha M GirgisDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Tamara Reyes-RoblesDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Rita ChanDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Aidan O'MalleyDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Peter BuckleyJanssen Research & Development LLC, 1400 McKean Road, Spring House, PA 19477, USA.
Nikollaq VozhillaDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Marilyn T VasquezDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Johnny SuKeenan Research Centre, St Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
Michael SugiyamaKeenan Research Centre, St Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
Stephen T YeungDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Maryaline CoffreDepartment of Pathology, New York University School of Medicine, New York, NY, USA.
Sofia BajwaDepartment of Pathology, New York University School of Medicine, New York, NY, USA.
Eric ChenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Patricia MartinKimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Sang Y KimDepartment of Pathology, New York University School of Medicine, New York, NY, USA; Office of Collaborative Sciences, NYU School of Medicine, New York, NY, USA; Department of Pathology, NYU School of Medicine, New York, NY, USA.
Cynthia LoomisDepartment of Pathology, New York University School of Medicine, New York, NY, USA; Office of Collaborative Sciences, NYU School of Medicine, New York, NY, USA; Department of Pathology, NYU School of Medicine, New York, NY, USA.
G Scott WorthenDepartment of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA; Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Bo ShopsinDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA; Division of Infectious Diseases, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA.
Kamal M KhannaDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Daniel WeinstockJanssen Research & Development LLC, 1400 McKean Road, Spring House, PA 19477, USA.
Anthony Simon LynchJanssen Research & Development LLC, 1400 McKean Road, Spring House, PA 19477, USA.
Sergei B KoralovDepartment of Pathology, New York University School of Medicine, New York, NY, USA.
P'ng LokeDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Ken CadwellDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Victor J TorresDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: victor.torres@nyulangone.org.
New York University · USJanssen (United States) · USSt. Michael's Hospital · CAUniversity of California, Berkeley · USUniversity of Pennsylvania · USUniversity of Toronto · CA
Funding
Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MMEDICAL SCIENTIST TRAININGT32GM007308 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PHILIPS, MARK REID · 1985 to 2019
$23.2MINFECTIOUS DISEASES &BASIC MICROBIOLOGICAL MECHANISMST32AI007180 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WEISER, JEFFREY NEAL · 1985 to 2022
$8.9MRedefining the role of autophagy in bacterial diseaseR01AI121244 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 2017 to 2026
$5.6MContribution of LukED to Staphylococcus aureus pathobiologyR01AI105129 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI TORRES, VICTOR J. · 2014 to 2023
$4.9MTraining Program in Immunology and Inflammation.T32AI100853 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Susan Ruth Schwab · 2012 to 2026
$4.5MMechanisms of MRSA intestinal colonizationR01AI140754 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SHOPSIN, BO · 2020 to 2024
$3.5MMicrobial triggers and molecular mechanisms of Th17 mediated airway inflammation-Resubmission-1R01HL125816 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KORALOV, SERGEI BORISOVICH · 2015 to 2019
$3.3MNon-Leukocidal Roles of Staphylococcus aureus Bi-component toxins in PathogenesisF30AI124606 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LUBKIN, ASHIRA LEAH · 2016 to 2019
$155kDetermining the role of autophagy in regulating the Staphylococcus aureus a-toxin receptor ADAM10F31HL137304 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KELLER, MATTHEW DAVID · 2017 to 2019
$124kThe Role of Autophagy During in vivo Salmonella InfectionF31DK111139 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARTIN, PATRICIA · 2016 to 2017
$88kNCI NIH HHS P30 CA016087NHLBI NIH HHS F31 HL137304NHLBI NIH HHS R01 HL125816NIAID NIH HHS F30 AI124606NIAID NIH HHS R01 AI105129NIAID NIH HHS R01 AI121244NIAID NIH HHS R01 AI140754NIAID NIH HHS T32 AI007180NIAID NIH HHS T32 AI100853NIDDK NIH HHS F31 DK111139NIGMS NIH HHS T32 GM007308
Abstract
The pathogenesis of Staphylococcus aureus is thought to depend on the production of pore-forming leukocidins that kill leukocytes and lyse erythrocytes. Two leukocidins, Leukocidin ED (LukED) and γ-Hemolysin AB (HlgAB), are necessary and sufficient to kill mice upon infection and toxin challenge. We demonstrate that LukED and HlgAB cause vascular congestion and derangements in vascular fluid distribution that rapidly cause death in mice. The Duffy antigen receptor for chemokines (DARC) on endothelial cells, rather than leukocytes or erythrocytes, is the critical target for lethality. Consistent with this, LukED and HlgAB injure primary human endothelial cells in a DARC-dependent manner, and mice with DARC-deficient endothelial cells are resistant to toxin-mediated lethality. During bloodstream infection in mice, DARC targeting by S. aureus causes increased tissue damage, organ dysfunction, and host death. The potential for S. aureus leukocidins to manipulate vascular integrity highlights the importance of these virulence factors.
Indexed as
AnimalsBacterial ProteinsBacterial ToxinsCells, CulturedCell SurvivalDisease Models, AnimalDuffy Blood-Group SystemEndothelial CellsExotoxinsHemolysin ProteinsHumansMiceMice, KnockoutModels, BiologicalReceptors, Cell SurfaceStaphylococcal InfectionsACKR1 protein, humanBacterial ProteinsBacterial ToxinsDuffy Blood-Group SystemExotoxinsgamma-hemolysin, Staphylococcus aureusHemolysin ProteinsLukD protein, Staphylococcus aureusLukE protein, Staphylococcus aureusReceptors, Cell SurfaceACKR1DARCendothelial cellsHlgABleukocidinLukEDStaphylococcus aureus
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