{"doi":"10.1101/2025.09.09.673684","title":"Cell cycle dependent variation in endocytosis drives phenotypic diversity in <i>M. tuberculosis</i>","abstract":"Abstract Cell-to-cell heterogeneity is a hallmark of biology, yet how host variability shapes intracellular pathogen phenotypes is unclear. Using single cell approaches and redox-sensitive Mycobacterium tuberculosis reporters, we reveal that interphase-driven shifts in endocytic capacity create distinct intracellular niches. Bacilli residing in high-endocytic G2 cells adopt more oxidized redox states, whereas those in low-endocytic G1 cells remain reduced, generating phenotypic diversity within a single infected population. Experimental manipulation of host cell cycle stage reprograms endocytic capacity and intrabacterial redox, establishing a causal link between host state and pathogen diversification. Notably, the finding that the cell cycle regulates endocytic capacity constitutes a fundamental cell-biological discovery with broad implications. This variability persists in post-differentiated macrophages, indicating that proliferative history imprints functional diversity onto innate immune cells. Together, these results identify interphase-regulated endocytosis as a host-intrinsic mechanism that shapes Mycobacterium tuberculosis phenotypes and suggest new host-directed avenues to influence infection trajectories and persistence.","journal":"eLife","year":2025,"id":559012,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"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":1460236,"name":"Sandhya Krishnan Radhakrishnan","orcid":null,"position":1,"is_corresponding":false},{"id":1460237,"name":"Hitakshi Vijay","orcid":null,"position":2,"is_corresponding":false},{"id":1460238,"name":"Neilay Bhalerao","orcid":null,"position":3,"is_corresponding":false},{"id":1459763,"name":"Sahanawaz Molla","orcid":"0000-0002-2811-0485","position":4,"is_corresponding":false},{"id":1460239,"name":"Anton Iyer","orcid":null,"position":5,"is_corresponding":false},{"id":691114,"name":"Shaon Chakrabarti","orcid":"0000-0002-7429-5927","position":6,"is_corresponding":false},{"id":378324,"name":"Varadharajan Sundaramurthy","orcid":"0000-0003-2562-8518","position":7,"is_corresponding":false},{"id":649267,"name":"Neeraja Subhash","orcid":"0000-0002-0241-1984","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","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":[]}