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

Abstract

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.

Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of Mycobacterium Tuberculosis from Iran

“…Khosravi et al reported embA mutation from EMB-susceptible strains [47]. Additionally, Sun et al revealed that 82.6% of EMB-resistant isolates from China had at least a mutation in the embABC locus, but contrary to this study, they were located mostly in the embA and embB upstream region [48].…”

Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol

“…3F and 3G). We thus suggest that ethambutol preferentially binds to EmbB and EmbC rather than to EmbA, a conclusion in line with clinical drug resistance studies (3)(4)(5)(36)(37)(38)(39)(40). When superimposing the EmbB (or EmbC) subunits in complex with ethambutol and disaccharide, we found that they overlapped within a high degree of similarity ( (Fig.…”

“…EmbC, which are involved in cell wall biosynthesis are regarded as the targets of ethambutol, since mutations to these proteins result in TB strains that are clinically resistant to this drug, noting that the majority of these resistance sites occur within EmbB (2)(3)(4)(5).…”

Evaluation of the QuantaMatrix Multiplexed Assay Platform for Molecular Diagnosis of Multidrug- and Extensively Drug-Resistant Tuberculosis Using Clinical Strains Isolated in Myanmar

“…This low detection rate could be attributed to a lack of appropriate probes. EMB resistance occurs most frequently at codons 306, 406, and 497 in the embB gene [26,27]; however, we designed probes related only to codon 306. Second, this study was conducted using only selected strains, including a high proportion of drug-resistant strains, and the performance evaluation was mainly focused on the detection of resistance.…”