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Mycobacterium tuberculosis releases an antacid that remodels phagosomes.
Buter, Jeffrey; Cheng, Tan-Yun; Ghanem, Marwan; Grootemaat, Anita E; Raman, Sahadevan; Feng, Xinxin; Plantijn, Ashmir R; Ennis, Thomas; Wang, Joyce; Cotton, Rachel N; Layre, Emilie; Ramnarine, Alexandrea K; Mayfield, Jacob A; Young, David C; Jezek Martinot, Amanda; Siddiqi, Noman; Wakabayashi, Shoko; Botella, Helene; Calderon, Roger; Murray, Megan; Ehrt, Sabine; Snider, Barry B; Reed, Michael B; Oldfield, Eric; Tan, Shumin; Rubin, Eric J; Behr, Marcel A; van der Wel, Nicole N; Minnaard, Adriaan J; Moody, D Branch.
Afiliación
  • Buter J; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Cheng TY; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Ghanem M; Infectious Diseases and Immunity in Global Health, McGill University Health Centre Research Institute, McGill International TB Centre, Montreal, Canada.
  • Grootemaat AE; Electron Microscopy Center Amsterdam, Department of Medical Biology, Amsterdam UMC, Amsterdam, the Netherlands.
  • Raman S; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Feng X; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Plantijn AR; Stratingh Institute for Chemistry, University of Groningen, Groningen, the Netherlands.
  • Ennis T; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Wang J; Infectious Diseases and Immunity in Global Health, McGill University Health Centre Research Institute, McGill International TB Centre, Montreal, Canada.
  • Cotton RN; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Layre E; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Ramnarine AK; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Mayfield JA; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Young DC; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Jezek Martinot A; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Siddiqi N; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Wakabayashi S; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Botella H; Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.
  • Calderon R; Socios en Salud Sucursal Peru, Lima, Peru.
  • Murray M; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
  • Ehrt S; Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.
  • Snider BB; Department of Chemistry, Brandeis University, Waltham, MA, USA.
  • Reed MB; Infectious Diseases and Immunity in Global Health, McGill University Health Centre Research Institute, McGill International TB Centre, Montreal, Canada.
  • Oldfield E; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Tan S; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
  • Rubin EJ; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Behr MA; Infectious Diseases and Immunity in Global Health, McGill University Health Centre Research Institute, McGill International TB Centre, Montreal, Canada.
  • van der Wel NN; Electron Microscopy Center Amsterdam, Department of Medical Biology, Amsterdam UMC, Amsterdam, the Netherlands.
  • Minnaard AJ; Stratingh Institute for Chemistry, University of Groningen, Groningen, the Netherlands.
  • Moody DB; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. bmoody@bwh.harvard.edu.
Nat Chem Biol ; 15(9): 889-899, 2019 09.
Article en En | MEDLINE | ID: mdl-31427817
Mycobacterium tuberculosis (Mtb) is the world's most deadly pathogen. Unlike less virulent mycobacteria, Mtb produces 1-tuberculosinyladenosine (1-TbAd), an unusual terpene nucleoside of unknown function. In the present study 1-TbAd has been shown to be a naturally evolved phagolysosome disruptor. 1-TbAd is highly prevalent among patient-derived Mtb strains, where it is among the most abundant lipids produced. Synthesis of TbAd analogs and their testing in cells demonstrate that their biological action is dependent on lipid linkage to the 1-position of adenosine, which creates a strong conjugate base. Furthermore, C20 lipid moieties confer passage through membranes. 1-TbAd selectively accumulates in acidic compartments, where it neutralizes the pH and swells lysosomes, obliterating their multilamellar structure. During macrophage infection, a 1-TbAd biosynthesis gene (Rv3378c) confers marked phagosomal swelling and intraphagosomal inclusions, demonstrating an essential role in regulating the Mtb cellular microenvironment. Although macrophages kill intracellular bacteria through phagosome acidification, Mtb coats itself abundantly with antacid.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fagosomas / Lípidos / Antiácidos / Mycobacterium tuberculosis Tipo de estudio: Prevalence_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Nat Chem Biol Asunto de la revista: BIOLOGIA / QUIMICA Año: 2019 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: Fagosomas / Lípidos / Antiácidos / Mycobacterium tuberculosis Tipo de estudio: Prevalence_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Nat Chem Biol Asunto de la revista: BIOLOGIA / QUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos