title: Role of embCAB gene mutations in ethambutol resistance in Mycobacterium tuberculosis isolates from India.
abstract: In the present study, ethambutol (EMB) resistance-associated mutations were characterised in the embCAB genes of clinical isolates of Mycobacterium tuberculosis (MTB) collected in India. Thirty MTB isolates were tested for their susceptibility to first-line antitubercular drugs using the Löwenstein-Jensen proportion method, and EMB minimum inhibitory concentrations of MTB isolates were determined by the resazurin microtitre assay. Sequencing of various regions of the embCAB genes was performed to identify EMB resistance-associated mutations. Mutations of embB306 were detected in 15 of 23 EMB-resistant MTB isolates. Three EMB-resistant isolates had mutations at codon 270 of the embC gene, two of which also harboured embB306 mutations. No mutation was identified in the embA gene. All seven EMB-sensitive MTB isolates had the wild-type embCAB sequence. In summary, embB306 mutations were associated with EMB resistance, and mutation at codon 270 of the embC gene may contribute to high-level EMB resistance in some MTB isolates.
authors.affiliation: Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Indian Council of Medical Research, Dr M. Miyazaki Marg, Tajganj, Agra 282001, India.
authors.forename: G P S
authors.initials: GP
authors.lastname: Jadaun
authors.forename: Ram
authors.initials: R
authors.lastname: Das
authors.forename: Prashant
authors.initials: P
authors.lastname: Upadhyay
authors.forename: D S
authors.initials: DS
authors.lastname: Chauhan
authors.forename: V D
authors.initials: VD
authors.lastname: Sharma
authors.forename: V M
authors.initials: VM
authors.lastname: Katoch
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D003470:Culture Media; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004977:Ethambutol / Q000494:pharmacology*; D006801:Humans; D007194:India; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D010078:Oxazines / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000382:microbiology; D014966:Xanthenes / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin; D004977:Ethambutol