Cargando…
The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection
Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200153/ https://www.ncbi.nlm.nih.gov/pubmed/32369020 http://dx.doi.org/10.7554/eLife.55692 |
_version_ | 1783529278189600768 |
---|---|
author | Giraud-Gatineau, Alexandre Coya, Juan Manuel Maure, Alexandra Biton, Anne Thomson, Michael Bernard, Elliott M Marrec, Jade Gutierrez, Maximiliano G Larrouy-Maumus, Gérald Brosch, Roland Gicquel, Brigitte Tailleux, Ludovic |
author_facet | Giraud-Gatineau, Alexandre Coya, Juan Manuel Maure, Alexandra Biton, Anne Thomson, Michael Bernard, Elliott M Marrec, Jade Gutierrez, Maximiliano G Larrouy-Maumus, Gérald Brosch, Roland Gicquel, Brigitte Tailleux, Ludovic |
author_sort | Giraud-Gatineau, Alexandre |
collection | PubMed |
description | Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections. |
format | Online Article Text |
id | pubmed-7200153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72001532020-05-06 The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection Giraud-Gatineau, Alexandre Coya, Juan Manuel Maure, Alexandra Biton, Anne Thomson, Michael Bernard, Elliott M Marrec, Jade Gutierrez, Maximiliano G Larrouy-Maumus, Gérald Brosch, Roland Gicquel, Brigitte Tailleux, Ludovic eLife Immunology and Inflammation Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections. eLife Sciences Publications, Ltd 2020-05-04 /pmc/articles/PMC7200153/ /pubmed/32369020 http://dx.doi.org/10.7554/eLife.55692 Text en © 2020, Giraud-Gatineau et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Giraud-Gatineau, Alexandre Coya, Juan Manuel Maure, Alexandra Biton, Anne Thomson, Michael Bernard, Elliott M Marrec, Jade Gutierrez, Maximiliano G Larrouy-Maumus, Gérald Brosch, Roland Gicquel, Brigitte Tailleux, Ludovic The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
title | The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
title_full | The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
title_fullStr | The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
title_full_unstemmed | The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
title_short | The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
title_sort | antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200153/ https://www.ncbi.nlm.nih.gov/pubmed/32369020 http://dx.doi.org/10.7554/eLife.55692 |
work_keys_str_mv | AT giraudgatineaualexandre theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT coyajuanmanuel theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT maurealexandra theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT bitonanne theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT thomsonmichael theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT bernardelliottm theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT marrecjade theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT gutierrezmaximilianog theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT larrouymaumusgerald theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT broschroland theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT gicquelbrigitte theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT tailleuxludovic theantibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT giraudgatineaualexandre antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT coyajuanmanuel antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT maurealexandra antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT bitonanne antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT thomsonmichael antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT bernardelliottm antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT marrecjade antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT gutierrezmaximilianog antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT larrouymaumusgerald antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT broschroland antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT gicquelbrigitte antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection AT tailleuxludovic antibioticbedaquilineactivateshostmacrophageinnateimmuneresistancetobacterialinfection |