%0 Journal Article %A Giraud-Gatineau, Alexandre %A Coya, Juan Manuel %A Maure, Alexandra %A Biton, Anne %A Thomson, Michael %A Bernard, Elliott M %A Marrec, Jade %A Gutierrez, Maximiliano G %A Larrouy-Maumus, GĂ©rald %A Brosch, Roland %A Gicquel, Brigitte %A Tailleux, Ludovic %D 2020 %T The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection. %U https://crick.figshare.com/articles/journal_contribution/The_antibiotic_bedaquiline_activates_host_macrophage_innate_immune_resistance_to_bacterial_infection_/12301394 %2 https://crick.figshare.com/ndownloader/files/22676084 %K antibiotics %K host-pathogen interaction %K human %K immunology %K infectious disease %K inflammation %K innate immunity %K macrophages %K microbiology %K tuberculosis %K Gutierrez FC001092 %K 0601 Biochemistry and Cell Biology %X 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. %I The Francis Crick Institute