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Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2+ DRG sensory neurons.
Yang, Nicole J; Isensee, Jörg; Neel, Dylan V; Quadros, Andreza U; Zhang, Han-Xiong Bear; Lauzadis, Justas; Liu, Sai Man; Shiers, Stephanie; Belu, Andreea; Palan, Shilpa; Marlin, Sandra; Maignel, Jacquie; Kennedy-Curran, Angela; Tong, Victoria S; Moayeri, Mahtab; Röderer, Pascal; Nitzsche, Anja; Lu, Mike; Pentelute, Bradley L; Brüstle, Oliver; Tripathi, Vineeta; Foster, Keith A; Price, Theodore J; Collier, R John; Leppla, Stephen H; Puopolo, Michelino; Bean, Bruce P; Cunha, Thiago M; Hucho, Tim; Chiu, Isaac M.
Afiliación
  • Yang NJ; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Isensee J; Translational Pain Research, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
  • Neel DV; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Quadros AU; Center for Research in Inflammatory Diseases, Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
  • Zhang HB; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Lauzadis J; Department of Anesthesiology, Stony Brook Medicine, Stony Brook, NY, USA.
  • Liu SM; Ipsen Bioinnovation Ltd, Abingdon, UK.
  • Shiers S; Department of Neuroscience, Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX, USA.
  • Belu A; Translational Pain Research, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
  • Palan S; Ipsen Bioinnovation Ltd, Abingdon, UK.
  • Marlin S; Ipsen Bioinnovation Ltd, Abingdon, UK.
  • Maignel J; Ipsen Innovation, Les Ulis, France.
  • Kennedy-Curran A; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Tong VS; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Moayeri M; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Röderer P; Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
  • Nitzsche A; Cellomics Unit, LIFE & BRAIN GmbH, Bonn, Germany.
  • Lu M; Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
  • Pentelute BL; Cellomics Unit, LIFE & BRAIN GmbH, Bonn, Germany.
  • Brüstle O; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Tripathi V; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Foster KA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Price TJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Collier RJ; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Leppla SH; Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
  • Puopolo M; Ipsen Bioinnovation Ltd, Abingdon, UK.
  • Bean BP; Ipsen Bioinnovation Ltd, Abingdon, UK.
  • Cunha TM; Department of Neuroscience, Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX, USA.
  • Hucho T; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Chiu IM; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Neurosci ; 25(2): 168-179, 2022 02.
Article en En | MEDLINE | ID: mdl-34931070
Bacterial products can act on neurons to alter signaling and function. In the present study, we found that dorsal root ganglion (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes edema factor (EF) and lethal factor (LF). Intrathecal administration of edema toxin (ET (PA + EF)) targeted DRG neurons and induced analgesia in mice. ET inhibited mechanical and thermal sensation, and pain caused by formalin, carrageenan or nerve injury. Analgesia depended on ANTXR2 expressed by Nav1.8+ or Advillin+ neurons. ET modulated protein kinase A signaling in mouse sensory and human induced pluripotent stem cell-derived sensory neurons, and attenuated spinal cord neurotransmission. We further engineered anthrax toxins to introduce exogenous protein cargoes, including botulinum toxin, into DRG neurons to silence pain. Our study highlights interactions between a bacterial toxin and nociceptors, which may lead to the development of new pain therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus anthracis / Toxinas Bacterianas / Células Madre Pluripotentes Inducidas / Carbunco Límite: Animals / Humans Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus anthracis / Toxinas Bacterianas / Células Madre Pluripotentes Inducidas / Carbunco Límite: Animals / Humans Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos