{"doi":"10.1093/cid/ciad596","title":"Genotype–Phenotype Characterization of Serial <i>Mycobacterium tuberculosis</i> Isolates in Bedaquiline-Resistant Tuberculosis","abstract":"BACKGROUND: Emerging resistance to bedaquiline (BDQ) threatens to undermine advances in the treatment of drug-resistant tuberculosis (DRTB). Characterizing serial Mycobacterium tuberculosis (Mtb) isolates collected during BDQ-based treatment can provide insights into the etiologies of BDQ resistance in this important group of DRTB patients. METHODS: We measured mycobacteria growth indicator tube (MGIT)-based BDQ minimum inhibitory concentrations (MICs) of Mtb isolates collected from 195 individuals with no prior BDQ exposure who were receiving BDQ-based treatment for DRTB. We conducted whole-genome sequencing on serial Mtb isolates from all participants who had any isolate with a BDQ MIC >1 collected before or after starting treatment (95 total Mtb isolates from 24 participants). RESULTS: Sixteen of 24 participants had BDQ-resistant TB (MGIT MIC ≥4 µg/mL) and 8 had BDQ-intermediate infections (MGIT MIC = 2 µg/mL). Participants with pre-existing resistance outnumbered those with resistance acquired during treatment, and 8 of 24 participants had polyclonal infections. BDQ resistance was observed across multiple Mtb strain types and involved a diverse catalog of mmpR5 (Rv0678) mutations, but no mutations in atpE or pepQ. Nine pairs of participants shared genetically similar isolates separated by <5 single nucleotide polymorphisms, concerning for potential transmitted BDQ resistance. CONCLUSIONS: BDQ-resistant TB can arise via multiple, overlapping processes, including transmission of strains with pre-existing resistance. Capturing the within-host diversity of these infections could potentially improve clinical diagnosis, population-level surveillance, and molecular diagnostic test development.","journal":"Clinical Infectious Diseases","year":2023,"id":336641,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9051,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1067495,"name":"Linrui Tang","orcid":"0000-0003-0144-0019","position":1,"is_corresponding":false},{"id":433640,"name":"Shaheed Vally Omar","orcid":"0000-0001-6983-1636","position":2,"is_corresponding":false},{"id":1067496,"name":"Lavania Joseph","orcid":"0000-0003-0734-7149","position":3,"is_corresponding":false},{"id":292884,"name":"Graeme Meintjes","orcid":"0000-0003-1196-4414","position":4,"is_corresponding":false},{"id":110248,"name":"Gary Maartens","orcid":"0000-0003-3080-6606","position":5,"is_corresponding":false},{"id":308893,"name":"Sean Wasserman","orcid":"0000-0002-3508-6719","position":6,"is_corresponding":false},{"id":431025,"name":"Neha Shah","orcid":"0000-0002-9575-9161","position":7,"is_corresponding":false},{"id":3674,"name":"Maha R. Farhat","orcid":"0000-0002-3871-5760","position":8,"is_corresponding":false},{"id":308895,"name":"Neel R. Gandhi","orcid":"0000-0002-1665-299X","position":9,"is_corresponding":false},{"id":433639,"name":"Nazir Ismail","orcid":"0000-0001-7696-3776","position":10,"is_corresponding":false},{"id":308894,"name":"James C.M. Brust","orcid":"0000-0003-3362-1818","position":11,"is_corresponding":false},{"id":299597,"name":"Barun Mathema","orcid":"0000-0003-2772-479X","position":12,"is_corresponding":false},{"id":237672,"name":"Tyler S. Brown","orcid":"0000-0003-2559-2789","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:10:21.947540Z","pmid":"37874928","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":[]}