Different Contributions of embB and ubiA Mutations to Variable Level of Ethambutol Resistance in Mycobacterium tuberculosis Isolates.

Autor:	Nan XT; 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., Li MC; 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., Xiao TY; Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People's Republic of China., Liu HC; 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., Lin SQ; College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People's Republic of China., Wang W; 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., Qian C; Beijing Center for Disease Control and Prevention, Beijing, 100013, People's Republic of China., Hang H; 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., Li GL; 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., Zhao XQ; 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., Wan KL; 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., Zhao LL; 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.
Jazyk:	angličtina
Zdroj:	Infection and drug resistance [Infect Drug Resist] 2024 Jul 18; Vol. 17, pp. 3125-3132. Date of Electronic Publication: 2024 Jul 18 (Print Publication: 2024).
DOI:	10.2147/IDR.S466371
Abstrakt:	Objective: To explore the association between the variant mutations within embB and ubiA , and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis ( M. tuberculosis ) isolates. Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA 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 embB and ubiA . Statistical analysis indicated that embB 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 ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA 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 embB and ubiA contributed to the different levels of EMB resistance. Competing Interests: All authors have no competing interests in this work. (© 2024 Nan et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu