title: Mutations in the embB gene and their association with ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates from Poland.
abstract: Ethambutol (EMB) continues to be used as part of a standard drug regimen for the treatment of tuberculosis (TB). Mutations in the embB gene and those within its conserved EMB resistance determining region (ERDR) in particular have repeatedly been associated with resistance to EMB in Mycobacterium tuberculosis. The aim of this study was to examine the mutational "hot spots" in the embB gene, including the ERDR, among multidrug-resistant (MDR) M. tuberculosis clinical isolates and to find a possible association between embB mutations and resistance to EMB. An 863-bp fragment of the embB gene was sequenced in 17 EMB-resistant and 33 EMB-susceptible MDR-TB isolates. In total, eight embB mutation types were detected in 6 distinct codons of 27 (54%) M. tuberculosis isolates. Mutations in codon 306 were most common, found in both EMB-resistant (9) and EMB-susceptible (11) isolates. Only mutations in codons 406 and 507 were found exclusively in four and one EMB-resistant isolates, respectively. Sequence analysis of the ERDR in the embB gene is not sufficient for rapid detection of EMB resistance, and the codon 306 mutations are not good predictive markers of resistance to EMB.
authors.affiliation: Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Bakuła
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Płocka 26, 01-138 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Napiórkowska
authors.affiliation: Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Bielecki
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Płocka 26, 01-138 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Płocka 26, 01-138 Warsaw, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zwolska
authors.affiliation: Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jagielski
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004977:Ethambutol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D010430:Pentosyltransferases / Q000235:genetics*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000235:genetics
chemical_list: D004977:Ethambutol; C540269:EmbB protein, Mycobacterium tuberculosis; D010430:Pentosyltransferases