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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. [ABSTRACT FROM AUTHOR]

However, the number of high-level RFB isolates with low-level RIF MIC was only six, among which four isolates had RIF MICs of 64 µg/mL, very close to the MIC definition of high-level RIF MIC (128 µg/mL). Results MIC Results Of the 177 tested isolates, 106 (59.9%) were resistant to RIF and RFB, 21 (11.9%) were RIF-resistant and RFB-susceptible, and 50 (28.2%) were susceptible to RIF and RFB. Mutations D435V and L452P were significantly associated with only RIF resistance, but not RFB resistance, consistent with the prior data.[17],[32] Cases carrying the isolates with these two mutations may be RFB-susceptible and benefit from the RFB-containing treatment regimen. [Extracted from the article]

Tuberculosis (TB) from a tertiary care TB hospital in China. The emergence of drug-resistant TB, especially multidrug-resistant TB (MDR-TB) Drug resistant-TB can occur when appropriate anti-TB medications are used TB requires more expensive anti-TB drugs and longer ther- (6/18) of patients with MDR-TB were pre-XDR TB, pla-. [Extracted from the article]