{"doi":"10.1093/jac/dkx316","title":"Identification of novel mutations associated with cycloserine resistance in Mycobacterium tuberculosis","abstract":null,"journal":"Journal of Antimicrobial Chemotherapy","year":2017,"id":688880,"datarank":0.6414999178524083,"base_score":4.276666119016055,"endowment":4.276666119016055,"self_citation_contribution":0.6414999178524083,"citation_network_contribution":0.0,"self_endowment_contribution":0.6414999178524083,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"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":1211192,"name":"Shuo Zhang","orcid":"0000-0002-1841-1727","position":1,"is_corresponding":false},{"id":17373,"name":"Peng Cui","orcid":"0000-0002-4566-6223","position":2,"is_corresponding":false},{"id":306731,"name":"Wanliang Shi","orcid":null,"position":3,"is_corresponding":false},{"id":514458,"name":"Wenhong Zhang","orcid":"0000-0002-9165-3212","position":4,"is_corresponding":false},{"id":832049,"name":"Ying Zhang","orcid":"0000-0003-2194-7116","position":5,"is_corresponding":false},{"id":921773,"name":"Jiazhen Chen","orcid":"0000-0002-9023-3072","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification of novel mutations associated with cycloserine resistance in Mycobacterium tuberculosis","abstract":"d-Cycloserine is an important second-line drug used to treat MDR- and XDR-TB. However, the mechanisms of resistance to d-cycloserine are not well understood. Here we investigated the molecular basis of d-cycloserine resistance using in vitro-isolated resistant mutants. Mycobacterium tuberculosis H37Rv was subjected to mutant selection on 7H11 agar plates containing varying concentrations of d-cycloserine. A total of 18 d-cycloserine-resistant mutants were isolated and subjected to WGS. The identified mutations associated with d-cycloserine resistance were confirmed by PCR and Sanger sequencing. We identified mutations in 16 genes that are associated with d-cycloserine resistance. Interestingly, we found mutations only in alr (rv3423c) encoding alanine racemase, but not in other known d-cycloserine resistance-associated genes such as ddl, cycA or ald. Instead, we identified 13 new genes [rv0059, betP (rv0917), rv0221, rv1403c, rv1683, rv1726, gabD2 (rv1731), rv2749, sugI (rv3331), hisC2 (rv3772), the 5′ intergenic region of rv3345c and rv1435c, and the 3′ region of rv0759c] that had solo mutations associated with d-cycloserine resistance. Our findings indicate that the mechanisms of d-cycloserine resistance are more complex than previously thought and involve genes participating in different cellular functions such as lipid metabolism, methyltransferase, the stress response and transport systems. New mutations in diverse genes associated with d-cycloserine resistance have been identified that shed new light on the mechanisms of action and resistance of d-cycloserine. Future studies are needed to verify these findings in clinical strains so that molecular detection of d-cycloserine resistance for improved treatment of MDR-TB can be developed.","is_dataset_classified":null,"base_score":4.276666119016055,"endowment":4.276666119016055,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28961957","pmcid":"PMC5890659","openalex_id":"https://openalex.org/W4229957117","authors":[],"funders":[{"funder_name":"NIH","grant_id":"AI99512","title":null},{"funder_name":"NIH","grant_id":"AI108535","title":null},{"funder_name":"Key Technologies Research and Development Program of China","grant_id":"2013ZX10003001-002","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81471987","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81101226","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI108535","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI099512","title":null},{"funder_name":"National Institutes of Health","grant_id":"1R21AI108535-01","title":"Toxin-antitoxins & RpsA in TB drug resistance & persistence with HIV"}],"total_grants":8,"fwci":2.9466,"citation_percentile":0.91771945,"influential_citations":0,"citation_trend":[{"year":2018,"count":4},{"year":2019,"count":8},{"year":2020,"count":7},{"year":2021,"count":7},{"year":2022,"count":13},{"year":2023,"count":8},{"year":2024,"count":9},{"year":2025,"count":9},{"year":2026,"count":6}],"oa_status":"bronze","license":"CC BY NC ND","oa_locations":[{"url":"https://academic.oup.com/jac/article-pdf/72/12/3272/24332040/dkx316.pdf","host_type":"journal"},{"url":"https://academic.oup.com/jac/article-pdf/72/12/3272/24332040/dkx316.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/jac/article-pdf/72/12/3272/24332040/dkx316.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/jac/dkx316","host_type":"journal"},{"url":"http://europepmc.org/pmc/articles/PMC5890659","host_type":"repository"},{"url":"https://doi.org/10.1101/114116","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/28961957","host_type":""},{"url":"https://dx.doi.org/10.1101/114116","host_type":""},{"url":"http://dx.doi.org/10.1101/114116","host_type":""}],"fields_of_study":["Tuberculosis Research and Epidemiology","Mycobacterium research and diagnosis","Immunodeficiency and Autoimmune Disorders","0301 basic medicine","03 medical and health sciences","Antibiotics, Antitubercular","Cycloserine","DNA Mutational Analysis","Drug Resistance, Bacterial","Mutation","Mycobacterium tuberculosis","Polymerase Chain Reaction","Selection, Genetic","Whole Genome Sequencing"],"mesh_terms":["Mycobacterium tuberculosis","Cycloserine","Antibiotics, Antitubercular","Polymerase Chain Reaction","DNA Mutational Analysis","Drug Resistance, Bacterial","Mutation","Selection, Genetic","Whole Genome Sequencing"],"keywords":["Cycloserine","Biology","Mutant","Genetics","Mycobacterium tuberculosis","Microbiology","Mutation","Gene","Tuberculosis","Medicine","Antibiotics","Whole Genome Sequencing","DNA Mutational Analysis","Drug Resistance, Bacterial","Selection, Genetic","Antibiotics, Antitubercular","Polymerase Chain Reaction"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.18230789.v1","title":"Additional file 1 of A modified decision tree approach to improve the prediction and mutation discovery for drug resistance in Mycobacterium tuberculosis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.18230789","title":"Additional file 1 of A modified decision tree approach to improve the prediction and mutation discovery for drug resistance in Mycobacterium tuberculosis","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-19T20:04:55.510869Z","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":[]}