Mutations within Are Associated with Variable Level of Ethambutol Resistance in Mycobacterium tuberculosis Isolates from China.

The EmbCAB proteins have been considered a target for ethambutol (EMB). Mutations in are known to confer most EMB resistance. However, the knowledge about the effects of mutations on the EMB resistance level and about the role of mutation-mutation interactions is limited in China. Here, we sequenced among 125 isolates from China and quantified their EMB MICs by testing growth at 10 concentrations. Furthermore, a multivariate regression model was established to assess the effects of both individual mutations and multiple mutations. Our results revealed that in China, 82.6% of EMB-resistant isolates (71/86 isolates) harbored at least one mutation within Most of the mutations were located in the and upstream region. Several individual mutations and multiple mutations within this region contributed to the different levels of EMB resistance. Their effects were statistically significant. Additionally, there was an association between high-level EMB resistance and multiple mutations.