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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-03-01
Series:BMC Microbiology
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Online Access:https://doi.org/10.1186/s12866-025-03821-y
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Summary: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.
ISSN:1471-2180