{"doi":"10.1101/2025.07.14.664820","title":"Increased proportion of growth-arrested bacilli in acidic pH adaptation promotes <i>Mycobacterium tuberculosis</i> treatment survival","abstract":"(Mtb) to adapt its growth behavior in response to host environments promotes survival against immune and drug stressors. However, how these behaviors shift at the single-cell level remains poorly understood. Here, we show that Mtb adapts to acidic conditions by increasing the proportion of bacteria in a growth-arrested state, rather than uniformly slowing the growth rate of the entire population. This non-growing subpopulation exhibits greater tolerance to ethambutol. Clinical strains displayed higher proportions of growth-arrested cells under both neutral and acidic conditions, suggesting that growth arrest serves as a bet-hedging strategy during infection. Though the PhoPR two-component system contributes to regulating this non-growing state, we show that it is a partial regulator of the non-growing bacterial subpopulation and that additional transcriptional regulators are involved. Our study demonstrates that non-growing subpopulations of Mtb provide fitness benefits and are an active adaptation to environmental cues and not a passive consequence of stressors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":570271,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1401917,"name":"William Johnson","orcid":"0000-0003-0088-0063","position":1,"is_corresponding":false},{"id":244643,"name":"Maliwan Kamkaew","orcid":"0009-0003-2229-429X","position":2,"is_corresponding":false},{"id":569856,"name":"Morgan E. McNellis","orcid":"0000-0002-6055-262X","position":3,"is_corresponding":false},{"id":569854,"name":"Trever C. Smith","orcid":"0000-0002-1651-313X","position":4,"is_corresponding":false},{"id":1475622,"name":"Srinivasan Vijay","orcid":"0000-0003-3434-5608","position":5,"is_corresponding":false},{"id":418474,"name":"Nguyễn Thụy Thương Thương","orcid":"0000-0001-8733-692X","position":6,"is_corresponding":false},{"id":486013,"name":"Shumin Tan","orcid":"0000-0003-1093-2576","position":7,"is_corresponding":false},{"id":539737,"name":"Bree B. Aldridge","orcid":"0000-0003-2236-1424","position":8,"is_corresponding":false},{"id":984422,"name":"Eun Seon Chung","orcid":"0000-0003-4947-4541","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:57:07.857542Z","pmid":"40791516","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":[]}