Ethambutol (EMB) mono-resistance does not occur frequently and scanty data are available regarding the resistance mechanism of EMB. The present study analyses mutations in the embB gene in EMB-resistant Indian isolates of Mycobacterium tuberculosis. Thirty-seven isolates were collected from different parts of India and the 364 bp of embB gene involved in resistance to EMB was amplified by PCR and subjected to single-stranded conformational polymorphism (SSCP). Mutations associated with EMB resistance were found to be present mostly with isoniazid and rifampicin. SSCP showed altered mobility in 30/37 isolates. The most common mutation was observed at codon 306 in 9/22 isolates followed by 299 in 6/22 isolates. We have found novel mutations not reported so far at codon 239, 257, 282, 296, 299, 304 and 311. SSCP revealed 22 (73.3%) isolates had mutation in the 364 bp fragment of embB gene. Our results suggest that alterations in amino acid sequence could be present from position 239 to 311 and functional analysis of the genetic variants of embB protein may provide a possible mechanism for EMB resistance.
A. Garg, S. Srivastava, A. Ayyagari