Mutations within embCAB are associated with variable level of ethambutol resistance in Mycobacterium tuberculosis isolates from China [PublishAheadOfPrint]

The EmbCAB proteins have been considered a target for ethambutol (EMB). Mutations in the embCAB are known to confer most EMB resistance. However, knowledge about the effects of embCAB mutations on EMB resistance level and about the role of mutation-mutation interaction is limited in China. Here, we sequenced the embCAB among 125 Mycobacterium tuberculosis (M. tuberculosis) isolates from China and quantified their EMB minimum inhibitory concentration (MIC) by testing growth at 10 concentrations. Furthermore, a multivariate regression model was established to assess the effects of both individual mutation and multiple mutations. Our results revealed that in China, 82.6% of EMB-resistant isolates (71/86 isolates) harbored at least one mutation within embCAB. Most the mutations located in the embB and embA upstream region. Several individual mutation 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.

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