{"doi":"10.1101/2021.06.02.446746","title":"<i>Mycobacterium tuberculosis</i> H <sub>2</sub> S functions as a sink to modulate central metabolism, bioenergetics, and drug susceptibility","abstract":"Abstract H 2 S is a potent gasotransmitter in eukaryotes and bacteria. Host-derived H 2 S has been shown to profoundly alter M. tuberculosis ( Mtb ) energy metabolism and growth. However, compelling evidence for endogenous production of H 2 S and its role in Mtb physiology is lacking. We show that multidrug-resistant and drug-susceptible clinical Mtb strains produce H 2 S, whereas H 2 S production in non-pathogenic M. smegmatis is barely detectable. We identified Rv3684 (Cds1) as an H 2 S-producing enzyme in Mtb and show that cds1 disruption reduces, but does not eliminate, H 2 S production, suggesting the involvement of multiple genes in H 2 S production. We identified endogenous H 2 S to be an effector molecule that maintains bioenergetic homeostasis by stimulating respiration primarily via cytochrome bd . Importantly, H 2 S plays a key role in central metabolism by modulating the balance between oxidative phosphorylation and glycolysis, and functions as a sink to recycle sulfur atoms back to cysteine to maintain sulfur homeostasis. Lastly, Mtb -generated H 2 S regulates redox homeostasis and susceptibility to anti-TB drugs clofazimine and rifampicin. These findings reveal previously unknown facets of Mtb physiology and have implications for routine laboratory culturing, understanding drug susceptibility, and improved diagnostics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215473,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273292,"name":"Md. Aejazur Rahman","orcid":"0000-0002-2616-3372","position":1,"is_corresponding":false},{"id":273294,"name":"Barry Truebody","orcid":"0000-0001-7066-3916","position":2,"is_corresponding":false},{"id":273293,"name":"Jared S. Mackenzie","orcid":"0000-0002-3089-0900","position":3,"is_corresponding":false},{"id":273287,"name":"Vikram Saini","orcid":"0000-0002-0258-2871","position":4,"is_corresponding":false},{"id":273291,"name":"Dirk A. Lamprecht","orcid":"0000-0003-1066-9026","position":5,"is_corresponding":false},{"id":273295,"name":"John Adamson","orcid":"0000-0001-7651-2238","position":6,"is_corresponding":false},{"id":495514,"name":"Ritesh Rajesh Sevalkar","orcid":"0000-0002-1694-8854","position":7,"is_corresponding":false},{"id":276048,"name":"Jack R. Lancaster","orcid":null,"position":8,"is_corresponding":false},{"id":283181,"name":"Michael Berney","orcid":"0000-0002-4833-0573","position":9,"is_corresponding":false},{"id":273290,"name":"Joel N. Glasgow","orcid":"0000-0002-2842-7917","position":10,"is_corresponding":false},{"id":273298,"name":"Adrie J. C. Steyn","orcid":"0000-0001-9177-8827","position":11,"is_corresponding":false},{"id":273296,"name":"Tafara T. R. Kunota","orcid":"0000-0003-1743-9901","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:52:55.971300Z","pmid":null,"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":[]}