Different Contributions of and Mutations to Variable Level of Ethambutol Resistance in Isolates.

Infect Drug Resist

National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China.

Published: July 2024

AI Article Synopsis

  • * Researchers analyzed 146 isolates, identifying various mutations and assessing their impact on EMB resistance through minimum inhibitory concentration testing and statistical modeling.
  • * Results showed that certain mutations (Met306Val, Met306Ile, Gly406Ala, and Gln497Arg) were significantly related to EMB resistance, with some mutations strongly correlating with high-level resistance, highlighting the complex genetic factors influencing EMB susceptibility.

Article Abstract

Objective: To explore the association between the variant mutations within and , and the degree of ethambutol (EMB) resistance of () isolates.

Methods: A total of 146 isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within and among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance.

Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced and . Statistical analysis indicated that mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within accompanied with mutation presented exclusively in EMB-resistant isolates, four single mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates.

Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within and contributed to the different levels of EMB resistance.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268779PMC
http://dx.doi.org/10.2147/IDR.S466371DOI Listing

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