The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China
Abstract Objectives To assess the mutation effects of ethambutol (EMB) resistance-associated genes, including embCAB operon, ubiA, embR, and aftA, on the EMB resistance levels among multidrug-resistant tuberculosis (MDR-TB) isolates from China. Methods A total of 159 MDR-TB from China had their EMB...
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BMC
2025-03-01
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| Online Access: | https://doi.org/10.1186/s12866-025-03821-y |
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| author | Ma-chao Li Wei Wang Tong-yang Xiao Hai-can Liu Shi-qiang Lin Hao Hang Xiang-long Bo Xiao-tian Nan Cheng Qian Xue-ting Fan Xiu-qin Zhao Gui-lian Li Kang-Lin Wan Li-li Zhao |
| author_facet | Ma-chao Li Wei Wang Tong-yang Xiao Hai-can Liu Shi-qiang Lin Hao Hang Xiang-long Bo Xiao-tian Nan Cheng Qian Xue-ting Fan Xiu-qin Zhao Gui-lian Li Kang-Lin Wan Li-li Zhao |
| author_sort | Ma-chao Li |
| collection | DOAJ |
| description | Abstract Objectives To assess the mutation effects of ethambutol (EMB) resistance-associated genes, including embCAB operon, ubiA, embR, and aftA, on the EMB resistance levels among multidrug-resistant tuberculosis (MDR-TB) isolates from China. Methods A total of 159 MDR-TB from China had their EMB MICs quantified, and the sequences of the four ethambutol resistance-associated regions were analyzed. A multivariate regression model was established to evaluate the effects of mutations on EMB resistance. Results Our results showed that overall 95.6% (109/114 isolates) of EMB-resistant isolates harbored at least one mutation within the regions associated with EMB resistance. Most mutations were in embB, particularly in the embB300-500, and the embC-embA intergenic regions. Mutations in other genes were seldom seen and mainly occurred along with mutations in the embB or the embC-embA among the EMB-resistant isolates. DNA sequencing of the embB300-500 and the embC-embA was the most effective approach for detecting EMB resistance, with an accuracy of 91.2%. Nevertheless, some EMB-susceptible isolates still had a single mutation in the gene related to EMB resistance. Moreover, there was a significant correlation between EMB high-level resistance and multiple mutations. Conclusion Distinct individual mutations, as well as multiple concurrent mutations, within EMB resistance-associated genes, contributed to variable levels of EMB resistance. These results have broadened our understanding of the molecular characteristics of EMB resistance in China. |
| format | Article |
| id | doaj-art-37a015d3baaf41f4adb49086feb266cb |
| institution | OA Journals |
| issn | 1471-2180 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | BMC Microbiology |
| spelling | doaj-art-37a015d3baaf41f4adb49086feb266cb2025-08-20T02:01:35ZengBMCBMC Microbiology1471-21802025-03-012511910.1186/s12866-025-03821-yThe implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from ChinaMa-chao Li0Wei Wang1Tong-yang Xiao2Hai-can Liu3Shi-qiang Lin4Hao Hang5Xiang-long Bo6Xiao-tian Nan7Cheng Qian8Xue-ting Fan9Xiu-qin Zhao10Gui-lian Li11Kang-Lin Wan12Li-li Zhao13National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionDepartment of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionCollege of Life Science, Fujian Agriculture and Forestry UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionBeijing Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and PreventionAbstract Objectives To assess the mutation effects of ethambutol (EMB) resistance-associated genes, including embCAB operon, ubiA, embR, and aftA, on the EMB resistance levels among multidrug-resistant tuberculosis (MDR-TB) isolates from China. Methods A total of 159 MDR-TB from China had their EMB MICs quantified, and the sequences of the four ethambutol resistance-associated regions were analyzed. A multivariate regression model was established to evaluate the effects of mutations on EMB resistance. Results Our results showed that overall 95.6% (109/114 isolates) of EMB-resistant isolates harbored at least one mutation within the regions associated with EMB resistance. Most mutations were in embB, particularly in the embB300-500, and the embC-embA intergenic regions. Mutations in other genes were seldom seen and mainly occurred along with mutations in the embB or the embC-embA among the EMB-resistant isolates. DNA sequencing of the embB300-500 and the embC-embA was the most effective approach for detecting EMB resistance, with an accuracy of 91.2%. Nevertheless, some EMB-susceptible isolates still had a single mutation in the gene related to EMB resistance. Moreover, there was a significant correlation between EMB high-level resistance and multiple mutations. Conclusion Distinct individual mutations, as well as multiple concurrent mutations, within EMB resistance-associated genes, contributed to variable levels of EMB resistance. These results have broadened our understanding of the molecular characteristics of EMB resistance in China.https://doi.org/10.1186/s12866-025-03821-yMultidrug-resistant tuberculosisEthambutolResistanceMutation |
| spellingShingle | Ma-chao Li Wei Wang Tong-yang Xiao Hai-can Liu Shi-qiang Lin Hao Hang Xiang-long Bo Xiao-tian Nan Cheng Qian Xue-ting Fan Xiu-qin Zhao Gui-lian Li Kang-Lin Wan Li-li Zhao The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China BMC Microbiology Multidrug-resistant tuberculosis Ethambutol Resistance Mutation |
| title | The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China |
| title_full | The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China |
| title_fullStr | The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China |
| title_full_unstemmed | The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China |
| title_short | The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China |
| title_sort | implications of mutations in multiple genes associated with ethambutol resistance among multidrug resistant tuberculosis isolates from china |
| topic | Multidrug-resistant tuberculosis Ethambutol Resistance Mutation |
| url | https://doi.org/10.1186/s12866-025-03821-y |
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