Phthiocerol dimycocerosates from Mycobacterium tuberculosis increase the membrane activity of bacterial effectors and host receptors
| Autor: | Fadel Sayes, Serge Mazères, Valérie Guillet, Jacques Augenstreich, Roxane Simeone, Roland Brosch, Catherine Astarie-Dequeker, Evert Haanappel, Christian Chalut, Christophe Guilhot, Lionel Mourey |
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| Přispěvatelé: | Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the European Union's Horizon 2020 Research and Innovation Program (TBVAC2020, 643381), the Agence Nationale de la Recherche (ANR-10-LABX-62-IBEID, ANR-14-JAMR-001-02, and ANR-16-CE15-0003), the Fondation pour la Recherche Médicale FRM (DEQ20130326471 and DEQ20160334879), and the Center National de la Recherche Scientifique (CNRS). JA was a recipient of a Ph.D. scholarship from the French government., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-JAMR-0001,noTBsec,New intervention strategy for tuberculosis: blocking multiple essential targets(2014), ANR-16-CE15-0003,MTBLipVir,Analyse multi-échelle et multidisciplinaire des mécanismes intimes d'action des lipides de virulence de l'enveloppe de Mycobacterium tuberculosis(2016), European Project: 643381,H2020,H2020-PHC-2014-single-stage,TBVAC2020(2015), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
genetic structures [SDV]Life Sciences [q-bio] Cell lcsh:QR1-502 receptors [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity lcsh:Microbiology Virulence factor Cellular and Infection Microbiology phthiocerol dimycocerosates EsxA [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Receptor Lipid bilayer ComputingMilieux_MISCELLANEOUS 0303 health sciences biology Chemistry Effector 030302 biochemistry & molecular biology Brief Research Report Lipids macrophages 3. Good health Cell biology Infectious Diseases [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology medicine.anatomical_structure membranes [SDV.IMM]Life Sciences [q-bio]/Immunology Microbiology (medical) 030106 microbiology Immunology Virulence Microbiology complement receptor 3 03 medical and health sciences Immune system Phagocytosis medicine Membrane activity 030304 developmental biology membranolytic activity Mycobacterium tuberculosis biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology 030104 developmental biology sense organs [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Mycobacterium |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, 2020, 10, pp.420. ⟨10.3389/fcimb.2020.00420⟩ Frontiers in Cellular and Infection Microbiology, Frontiers, 2020, 10, pp.420. ⟨10.3389/fcimb.2020.00420⟩ Frontiers in Cellular and Infection Microbiology, Frontiers, 2020, 10, ⟨10.3389/fcimb.2020.00420⟩ Frontiers in Cellular and Infection Microbiology, Vol 10 (2020) |
| ISSN: | 2235-2988 |
| DOI: | 10.1101/2020.05.13.092585 |
| Popis: | Mycobacterium tuberculosis (Mtb) synthesizes a variety of atypical lipids that are exposed at the cell surface and help the bacterium infect macrophages and escape elimination by the cell’s immune responses. In the present study, we investigate the mechanism of action of one family of hydrophobic lipids, the phthiocerol dimycocerosates (DIM/PDIM), major lipid virulence factors. DIM are transferred from the envelope of Mtb to host membranes during infection. Using the polarity-sensitive fluorophore C-Laurdan, we visualized that DIM increase the membrane polarity of a supported lipid bilayer put in contact with mycobacteria, even beyond the site of contact. We observed that DIM activate the complement receptor 3, a predominant receptor for phagocytosis of Mtb by macrophages. DIM also increased the activity of membrane-permeabilizing effectors of Mtb, among which the virulence factor EsxA. This is consistent with previous observations that DIM help Mtb disrupt host cell membranes. Taken together, our data show that transferred DIM spread within the target membrane, remodel lipid organization and increase the activity of host cell receptors and bacterial effectors, diverting in a nonspecific manner host cell functions. We therefore bring new insight into the molecular mechanisms by which DIM increase Mtb’s capability to escape the cell’s immune responses. |
| Databáze: | OpenAIRE |
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