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Chan School of Public Health"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA762328"],"scientific_name":["Homo sapiens"],"tag":["xref:PubMed:35038923"],"long_description":["Macrophages are a protective replicative niche for Mycobacterium tuberculosis (Mtb) but can kill the infecting bacterium when appropriately activated. To identify mechanisms of clearance, we compared bacterial restriction by human macrophages after treatment with 26 compounds, including some currently in clinical trials for tuberculosis. All-trans-retinoic acid (ATRA), an active metabolite of vitamin A, drove the greatest increase in Mtb control. Bacterial clearance was transcriptionally and functionally associated with changes in macrophage cholesterol trafficking and lipid metabolism. To determine how these macrophage changes affected bacterial control, we performed the first Mtb CRISPR interference screen in an infection model, identifying Mtb genes specifically required to survive in ATRA-activated macrophages.  These data showed that ATRA treatment starves Mtb of cholesterol and the downstream metabolite propionyl-CoA. Supplementation with sources of propionyl-CoA, including cholesterol, abrogated the restrictive effect of ATRA.  This work demonstrates that targeting the coupled metabolism of Mtb and the macrophage improves control of infection, and that it is possible to genetically map the mode of bacterial death using CRISPR interference. Overall design: RNA-seq of human primary macrophages, uninfected or infected with Mycobacterium tuberculosis, treated with vehicle control or different retinoic acid receptor agonists."],"repository":["ENA"],"description_synonyms":["Tretin M, tretinoin, Monocyte Derived Macrophages, Refissa, trans-Retinoic Acid, Vitamin A, propionyl-CoA., 8E-tetraenoic acid, beta all trans Retinoic Acid, prevention, 6-trimethyl-1-cyclohexen-1-yl)-2, AGN 100335, Potassium Salt, Retinoic Acid, macrophage, Cholest-5-en-3-ol (3beta)-, Cordes vas, Mycobacterium tuberculosis var. hominis, Monocyte-Derived Macrophage, coenzyme A, 17alpha)-cholest-5-en-3-ol, 3, 4, 6, Retin-A, agranular plasmatocyte, prevention and control, Vesanoid, Stieva-A, 14beta, Retinoic acid, Retinoic, Bacillus tuberculosis, Bacterium tuberculosis, (3beta, all-trans-beta-Retinoic acid, reference sample, Renova, Salt, all trans Retinoic Acid, Cholest-5-en-3beta-ol, Atralin, Tretinoin Potassium Salt, Betarretin, Bone Marrow-Derived Macrophage, 8E)-3, trans Retinoic Acid, propionyl-coenzyme A, Tretinoin Sodium Salt, Epicholesterol, 6-trimethyl-1-cyclohexenyl)nona-2, Bone Marrow-Derived, preventive measures, beta-all-trans-Retinoic, Altreno, lamellocyte, Vitamin A Acid, (2E, trans-Retinoic, Veltin, Controlled, all-trans-vitamin A1 acid, macrophagocyte, Controlling, preventive therapy, Mycobacterium tuberculosis (Zopf 1883) Lehmann and Neumann 1896 (Approved Lists 1980), 3H-labeled, Tretinoin Zinc Salt, typical plasmatocyte, 8-all-trans-tetraenoic acid, 4E, Monocyte Derived, Dermairol, Tretinoin Potassium, monocyte-derived macrophage, Ro 1-5488, Tri-luma, Tretinoin, trans-retinoic acid, all-trans retinoic acid, all-trans-Retinoic Acid, 8-nonatetraenoic acid, Tretinoin Sodium, Monocyte-Derived, all-trans-vitamin A acid, Biacna, 6-trimethylcyclohex-1-enyl)nona-2, Retin A, retinoic acid, all-trans-tretinoin, all-trans-Retinoic, Cholesterin, 6-trimethyl-1-cyclohexene-1-yl)-2, Acide retinoique (French), Monocyte-Derived Macrophages, Macrophage, beta-Retinoic acid, Acid, tretinoina, Macrophages, prophylaxis, Mycobacterium tuberculosis H37Rv, 6E, Tretinoin Zinc, all-trans-retinoic acid, beta-all-trans-Retinoic Acid, tretinoinum, Bone Marrow Derived Macrophages, 6-trimethylcyclohexen-1-yl)nona-2E, propionyl-, Zinc Salt, Sodium Salt, 7-dimethyl-9-(2, all-(E)-retinoic acid, Avita, control, Bone Marrow-Derived Macrophages, vitamin A acid, granulocyte, Retisol-A, histiocyte, (all-E)-3, 8-tetraenoic acid, tretinoine, Mycobacterium tuberculosis typus humanus"],"name_synonyms":["Tretin M, tretinoin, Monocyte Derived Macrophages, Refissa, trans-Retinoic Acid, Vitamin A, propionyl-CoA., 8E-tetraenoic acid, beta all trans Retinoic Acid, prevention, 6-trimethyl-1-cyclohexen-1-yl)-2, AGN 100335, Potassium Salt, Retinoic Acid, macrophage, Cholest-5-en-3-ol (3beta)-, Cordes vas, Mycobacterium tuberculosis var. hominis, Monocyte-Derived Macrophage, coenzyme A, 17alpha)-cholest-5-en-3-ol, 3, 4, 6, Retin-A, agranular plasmatocyte, prevention and control, Vesanoid, Stieva-A, 14beta, Retinoic acid, Retinoic, Bacillus tuberculosis, Bacterium tuberculosis, (3beta, all-trans-beta-Retinoic acid, reference sample, Renova, Salt, all trans Retinoic Acid, Cholest-5-en-3beta-ol, Atralin, Tretinoin Potassium Salt, Betarretin, Bone Marrow-Derived Macrophage, 8E)-3, trans Retinoic Acid, propionyl-coenzyme A, Tretinoin Sodium Salt, Epicholesterol, 6-trimethyl-1-cyclohexenyl)nona-2, Bone Marrow-Derived, preventive measures, beta-all-trans-Retinoic, Altreno, lamellocyte, Vitamin A Acid, (2E, trans-Retinoic, Veltin, Controlled, all-trans-vitamin A1 acid, macrophagocyte, Controlling, preventive therapy, Mycobacterium tuberculosis (Zopf 1883) Lehmann and Neumann 1896 (Approved Lists 1980), 3H-labeled, Tretinoin Zinc Salt, typical plasmatocyte, 8-all-trans-tetraenoic acid, 4E, Monocyte Derived, Dermairol, Tretinoin Potassium, monocyte-derived macrophage, Ro 1-5488, Tri-luma, Tretinoin, trans-retinoic acid, all-trans retinoic acid, all-trans-Retinoic Acid, 8-nonatetraenoic acid, Tretinoin Sodium, Monocyte-Derived, all-trans-vitamin A acid, Biacna, 6-trimethylcyclohex-1-enyl)nona-2, Retin A, retinoic acid, all-trans-tretinoin, all-trans-Retinoic, Cholesterin, 6-trimethyl-1-cyclohexene-1-yl)-2, Acide retinoique (French), Monocyte-Derived Macrophages, Macrophage, beta-Retinoic acid, Acid, tretinoina, Macrophages, prophylaxis, Mycobacterium tuberculosis H37Rv, 6E, Tretinoin Zinc, all-trans-retinoic acid, beta-all-trans-Retinoic Acid, tretinoinum, Bone Marrow Derived Macrophages, 6-trimethylcyclohexen-1-yl)nona-2E, propionyl-, Zinc Salt, Sodium Salt, 7-dimethyl-9-(2, all-(E)-retinoic acid, Avita, control, Bone Marrow-Derived Macrophages, vitamin A acid, granulocyte, Retisol-A, histiocyte, (all-E)-3, 8-tetraenoic acid, tretinoine, Mycobacterium tuberculosis typus humanus"],"additional_accession":[]},"is_claimable":false,"name":"CRISPR interference reveals that all-trans-retinoic acid promotes macrophage control of Mycobacterium tuberculosis by limiting bacterial access to cholesterol and propionyl-CoA","description":"CRISPR interference reveals that all-trans-retinoic acid promotes macrophage control of Mycobacterium tuberculosis by limiting bacterial access to cholesterol and propionyl-CoA","dates":{"last_updated":"2025-09-24","first_public":"2021-12-23"},"accession":"PRJNA762328","cross_references":{"GEO":["GSE183912"],"taxon":["9606"],"PubMed":["35038923"]}}