Characterization of the most common embCAB gene mutations associated with ethambutol resistance in Mycobacterium tuberculosis isolates from Iran

Ethambutol (Emb) is one of the first-line drugs in the standard combination therapy for tuberculosis; however, due to the rapid increase in Emb resistance among clinical isolates of (MTB), early detection of Emb resistance is desirable. As the operon is considered involved in resistance to Emb, this study aimed to analyze the most common mutations within the operon among MTB isolates from Iran to find any correlations of these mutations with Emb resistance. A total of 307 clinical isolates of MTB were screened for Emb resistance by phenotypic drug-susceptibility testing. PCR amplification was performed on extracted DNA from all Emb-resistant and randomly selected Emb-susceptible isolates using sets of primers for various gene loci of , , and , followed by sequencing for the detection of most common alterations. In total, ten isolates showed resistance to Emb by phenotypic susceptibility testing (3.25%). The mutation rate in ten Emb-resistant MTB strains was 20% (n=2), comprising one mutation in (10%), at codon 306 Met-Val and one in (10%) at codon 270 Thr-Ile. A nonsynonymous mutation in the gene in one of the randomly selected Emb-susceptible isolates located in codon 330 Leu-Leu was also noticed. The majority of our Emb-resistant isolates (n=8, 80%) did not demonstrate the sequences investigated within the operon. As such, these mutations solely are insufficient for the development of complete resistance to Emb in MTB isolates. Additional mechanisms of resistance other than mutations in these sequences studied within the operon should also be considered.