Studies on mutations in embB locus in Indian clinical isolates of Mycobacterium tuberculosis having high degree of ethambutol resistance

摘要

Ethambutol [EMB: dextro-2.2'-(ethylenedumino)-di-l-butanol], a frontline antituberculosis drug, targets the mycobacterial cell wall. Genetic events resulting in structural mutations at the iembB locus have been proposed as a major mechanism for EMB resistance in iMycobacterium tuberculosis. In this study, mutations hi the iembB locus of Indian isolates and their correlation with the MIC levels in iM. tuberculosis have been investigated. We have sequenced and analysed 260 bp of the iembB gene region containing the hotspot association with EMB-resistance isolates of iM. tuberculosis in 39 EMB-resistant and 13 susceptible clinical isolates. Out of 39 resistant isolates, 17 (44%) had mutation in the iembB locus at codon 306, whereas the remaining 22 (56%) resistant and 13 sensitive isolates did not have any mutation in this region. Five different substitution mutations of ATG(Met) in the resistant strains were: GTG (Val) 41%, ATA (He) 29%, ATC (He) 18%, TTG (Leu) 6% and CTG (Leu) 6%. All these mutations at codon 306 were associated with a high degree of ethambutol-resistant phenotype. Results suggest that the iembB306 mutations might prove to be one of useful markers for detection of ethambutol resistance in isolates of iM. tuberculosis in India. Lack of mutation, however, does not rule out ethambutol resistance.