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Objectives <p>To assess the mutation effects of ethambutol (EMB) resistance-associated genes, including <i>embCAB</i> operon, <i>ubiA</i>, <i>embR</i>, and <i>aftA</i>, on the EMB resistance levels among multidrug-resistant tuberculosis (MDR-TB) isolates from China.</p> Methods <p>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.</p> Results <p>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 <i>embB</i>, particularly in the <i>embB</i>300-500, and the <i>embC-embA</i> intergenic regions. Mutations in other genes were seldom seen and mainly occurred along with mutations in the <i>embB</i> or the <i>embC-embA</i> among the EMB-resistant isolates. DNA sequencing of the <i>embB</i>300-500 and the <i>embC-embA</i> 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.</p> Conclusion <p>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.</p>

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The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月1日

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  • 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

摘要

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.