{"doi":"10.1038/s42003-024-06562-2","title":"Facile metabolic reprogramming distinguishes mycobacterial adaptation to hypoxia and starvation: ketosis drives starvation-induced persistence in M. bovis BCG","abstract":"Abstract Mycobacteria adapt to infection stresses by entering a reversible non-replicating persistence (NRP) with slow or no cell growth and broad antimicrobial tolerance. Hypoxia and nutrient deprivation are two well-studied stresses commonly used to model the NRP, yet little is known about the molecular differences in mycobacterial adaptation to these distinct stresses that lead to a comparable NRP phenotype. Here we performed a multisystem interrogation of the Mycobacterium bovis BCG (BCG) starvation response, which revealed a coordinated metabolic shift away from the glycolysis of nutrient-replete growth to depletion of lipid stores, lipolysis, and fatty acid ß-oxidation in NRP. This contrasts with BCG’s NRP hypoxia response involving a shift to cholesterol metabolism and triglyceride storage. Our analysis reveals cryptic metabolic vulnerabilities of the starvation-induced NRP state, such as their newfound hypersensitivity to H 2 O 2 . These observations pave the way for developing precision therapeutics against these otherwise drug refractory pathogens.","journal":"Communications Biology","year":2024,"id":454741,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1189905,"name":"Yok Hian Chionh","orcid":"0000-0002-4909-8382","position":1,"is_corresponding":false},{"id":149393,"name":"Megan E. McBee","orcid":null,"position":2,"is_corresponding":false},{"id":1189906,"name":"Fabian Hia","orcid":"0000-0002-7209-4312","position":3,"is_corresponding":false},{"id":612852,"name":"Duanduan Ma","orcid":"0000-0002-4753-0813","position":4,"is_corresponding":false},{"id":1011737,"name":"Cui Liang","orcid":"0000-0001-9356-825X","position":5,"is_corresponding":false},{"id":74509,"name":"Mariam L. Sharaf","orcid":null,"position":6,"is_corresponding":false},{"id":290532,"name":"Weiling Maggie Cai","orcid":null,"position":7,"is_corresponding":false},{"id":1190269,"name":"Watthanachai Jumpathong","orcid":null,"position":8,"is_corresponding":false},{"id":62836,"name":"Stuart S. Levine","orcid":"0000-0001-7363-562X","position":9,"is_corresponding":false},{"id":283178,"name":"Sylvie Alonso","orcid":"0000-0001-7044-414X","position":10,"is_corresponding":false},{"id":289582,"name":"Peter C. Dedon","orcid":"0000-0003-0011-3067","position":11,"is_corresponding":false},{"id":489743,"name":"Nick Davis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:03:12.720997Z","pmid":"39009734","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}