{"doi":"10.1128/aac.06003-11","title":"Efflux Pumps of Mycobacterium tuberculosis Play a Significant Role in Antituberculosis Activity of Potential Drug Candidates","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis</jats:named-content>\n            , we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and\n            <jats:sc>l</jats:sc>\n            -phenylalanyl-\n            <jats:sc>l</jats:sc>\n            -arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by\n            <jats:italic>Rv1218c</jats:italic>\n            , and the SMR (small multidrug resistance) class, encoded by\n            <jats:italic>Rv3065</jats:italic>\n            , appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by\n            <jats:italic>Rv0849</jats:italic>\n            and\n            <jats:italic>Rv1258c</jats:italic>\n            also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis</jats:named-content>\n            cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis</jats:named-content>\n            play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of\n            <jats:italic>Rv0849</jats:italic>\n            , a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2012,"id":611909,"datarank":0.7712495334753992,"base_score":5.14166355650266,"endowment":5.14166355650266,"self_citation_contribution":0.7712495334753992,"citation_network_contribution":0.0,"self_endowment_contribution":0.7712495334753992,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":170,"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":1575226,"name":"Neela Dinesh","orcid":null,"position":1,"is_corresponding":false},{"id":646758,"name":"Sreevalli Sharma","orcid":"0000-0001-6055-7853","position":2,"is_corresponding":false},{"id":1575227,"name":"Sanjana Kuruppath","orcid":null,"position":3,"is_corresponding":false},{"id":1575228,"name":"Anju V. Nair","orcid":null,"position":4,"is_corresponding":false},{"id":1575229,"name":"Umender Sharma","orcid":null,"position":5,"is_corresponding":false},{"id":1575225,"name":"Meenakshi Balganesh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Efflux Pumps of Mycobacterium tuberculosis Play a Significant Role in Antituberculosis Activity of Potential Drug Candidates","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis</jats:named-content>\n            , we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and\n            <jats:sc>l</jats:sc>\n            -phenylalanyl-\n            <jats:sc>l</jats:sc>\n            -arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by\n            <jats:italic>Rv1218c</jats:italic>\n            , and the SMR (small multidrug resistance) class, encoded by\n            <jats:italic>Rv3065</jats:italic>\n            , appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by\n            <jats:italic>Rv0849</jats:italic>\n            and\n            <jats:italic>Rv1258c</jats:italic>\n            also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis</jats:named-content>\n            cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis</jats:named-content>\n            play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of\n            <jats:italic>Rv0849</jats:italic>\n            , a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.\n          </jats:p>","is_dataset_classified":null,"base_score":5.14166355650266,"endowment":5.14166355650266,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22314527","pmcid":"PMC3346595","openalex_id":"https://openalex.org/W2044044282","authors":[],"funders":[],"total_grants":0,"fwci":7.0905,"citation_percentile":0.98019085,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":9},{"year":2014,"count":12},{"year":2015,"count":14},{"year":2016,"count":6},{"year":2017,"count":13},{"year":2018,"count":11},{"year":2019,"count":20},{"year":2020,"count":9},{"year":2021,"count":14},{"year":2022,"count":8},{"year":2023,"count":9},{"year":2024,"count":17},{"year":2025,"count":16},{"year":2026,"count":3}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/56/5/2643.full.pdf","host_type":"journal"},{"url":"https://aac.asm.org/content/aac/56/5/2643.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.06003-11","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.06003-11","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22314527","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3346595","host_type":"repository"}],"fields_of_study":["Tuberculosis Research and Epidemiology","Mycobacterium research and diagnosis","Infectious Diseases and Tuberculosis","ATP-Binding Cassette Transporters","Antitubercular Agents","Bacterial Proteins","Culture Media","Dipeptides","Drug Combinations","Drug Resistance, Multiple, Bacterial","Drug Synergism","Gene Knockout Techniques","Homologous Recombination","Humans","Microbial Sensitivity Tests","Mutation","Mycobacterium tuberculosis","Plasmids","Pyrazolones","Pyrroles","Tuberculosis, Pulmonary","Verapamil"],"mesh_terms":["Antitubercular Agents","Bacterial Proteins","Culture Media","Dipeptides","Drug Combinations","Drug Synergism","Humans","Microbial Sensitivity Tests","Mutation","Mycobacterium tuberculosis","Plasmids","Pyrroles","Tuberculosis, Pulmonary","Verapamil","ATP-Binding Cassette Transporters","Drug Resistance, Multiple, Bacterial","Pyrazolones","Gene Knockout Techniques","Homologous Recombination"],"keywords":["Efflux","Mycobacterium tuberculosis","Tuberculosis","Microbiology","Drug","Drug resistance","Medicine","Antibacterial agent","Antibiotics","Pharmacology","Virology","Biology","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":"2026-08-01T23:41:36.495708Z","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":[]}