{"doi":"10.1093/jac/dkq519","title":"Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis","abstract":null,"journal":"Journal of Antimicrobial Chemotherapy","year":2011,"id":607733,"datarank":0.7168685239667295,"base_score":4.77912349311153,"endowment":4.77912349311153,"self_citation_contribution":0.7168685239667295,"citation_network_contribution":0.0,"self_endowment_contribution":0.7168685239667295,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":118,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":832049,"name":"Ying Zhang","orcid":"0000-0003-2194-7116","position":1,"is_corresponding":false},{"id":1560604,"name":"Terrence C. K. Lau","orcid":null,"position":2,"is_corresponding":false},{"id":1560605,"name":"Ricky W. T. Lau","orcid":null,"position":3,"is_corresponding":false},{"id":1560606,"name":"Pak-Leung Ho","orcid":null,"position":4,"is_corresponding":false},{"id":1560607,"name":"Wing-Wai Yew","orcid":null,"position":5,"is_corresponding":false},{"id":1560608,"name":"Stephen K. W. Tsui","orcid":null,"position":6,"is_corresponding":false},{"id":1560609,"name":"Vincent C. C. Cheng","orcid":null,"position":7,"is_corresponding":false},{"id":72001,"name":"Kwok-Yung Yuen","orcid":"0000-0001-8700-4570","position":8,"is_corresponding":false},{"id":1560610,"name":"Wing-Cheong Yam","orcid":null,"position":9,"is_corresponding":false},{"id":1560603,"name":"Gilman Kit Hang Siu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis","abstract":"OBJECTIVES: Ninety-six percent of rifampicin resistance in Mycobacterium tuberculosis was shown to be associated with mutations inside the 81 bp rifampicin resistance-determining region (RRDR) located in the centre of the rpoB gene. The detection of rifampicin resistance by targeting the RRDR failed to match with a resistant phenotype in 4% of all cases. Our study aims to identify the mutations outside the RRDR that are associated with rifampicin resistance in M. tuberculosis. METHODS AND RESULTS: Among 50 rifampicin-resistant and 20 rifampicin-susceptible clinical isolates of M. tuberculosis, 2 of the rifampicin-resistant isolates did not harbour any known mutations in the RRDR. Sequencing analysis of the whole rpoB gene identified two rare mutations, V146F and I572F. A molecular structure model based on Thermus thermophilus RpoB revealed that both these substituted amino acids are located in close proximity to the rifampicin-binding pocket of the β-subunit. Substitutions of simple amino acids for bulky ones are likely to affect the protein-drug interaction. Cloning and transformation of the mutated rpoB gene into wild-type Mycobacterium smegmatis and M. tuberculosis successfully elevated the MIC of rifampicin and conferred the rifampicin resistance phenotype. CONCLUSIONS: Our study showed that amino acid positions 146 and 572 are associated with rifampicin resistance in M. tuberculosis in addition to the RRDR. Molecular assays for identifying rifampicin-resistant M. tuberculosis might be improved in terms of accuracy by including these two positions.","is_dataset_classified":null,"base_score":4.77912349311153,"endowment":4.77912349311153,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21393153","pmcid":null,"openalex_id":"https://openalex.org/W2148656381","authors":[],"funders":[],"total_grants":0,"fwci":2.9027,"citation_percentile":0.91096455,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":5},{"year":2014,"count":9},{"year":2015,"count":5},{"year":2016,"count":12},{"year":2017,"count":6},{"year":2018,"count":11},{"year":2019,"count":6},{"year":2020,"count":9},{"year":2021,"count":14},{"year":2022,"count":9},{"year":2023,"count":8},{"year":2024,"count":9},{"year":2025,"count":7},{"year":2026,"count":3}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://academic.oup.com/jac/article-pdf/66/4/730/17429258/dkq519.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/jac/dkq519","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21393153","host_type":"repository"},{"url":"http://hdl.handle.net/10722/157625","host_type":"repository"},{"url":"http://jac.oxfordjournals.org/cgi/content/short/dkq519v1","host_type":"repository"}],"fields_of_study":["Tuberculosis Research and Epidemiology","Mycobacterium research and diagnosis","Diagnosis and treatment of tuberculosis"],"mesh_terms":["Antitubercular Agents","Binding Sites","Cloning, Molecular","Humans","Mycobacterium tuberculosis","Rifampin","DNA-Directed RNA Polymerases","Tuberculosis","Thermus thermophilus","Amino Acid Substitution","Mycobacterium smegmatis","Mutation, Missense","Drug Resistance, Bacterial"],"keywords":["rpoB","Rifampicin","Mycobacterium tuberculosis","Microbiology","Biology","Tuberculosis","Genetics","Medicine","Antibiotics","Pathology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T06:55:34.975125Z","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":[]}