title: Frequency of mutational changes in the embB among the ethambutol-resistant strains of Mycobacterium tuberculosis in Iran.
abstract: BACKGROUND
  Early detection of drug resistant tuberculosis is one of the main priorities of TB control program. Ethambutol (EMB) is a first-line anti-TB drug that is effective for preventing treatment failures caused by Mycobacterium tuberculosis strains that are resistant to other drugs. The aim of this study was to sequence the embB gene to characterize the mutations causing resistance to EMB and to analyze the relationship between bacterial genotype and EMB resistance among M. tuberculosis isolates in Iran.
  
  
  METHODS
  A total of 20 M. tuberculosis isolates comprising 10 multidrug-resistant (MDR) and 10 non-MDR isolates, recovered from TB patients in four regions: Tehran, Isfahan, Zahedan, Khorasan, were analyzed. Mutational profiling was performed by amplifying and sequencing the embB gene. Spoligotyping was carried out to characterize the bacterial genotype.
  
  
  RESULTS
  Phenotypic EMB resistance was found in 13 strains. Mutations affecting ethambutol resistance-determining region (ERDR) of the embB were identified in 6 of 13 EMB-resistant isolates. The majority of these mutations resulted in amino acid substitution at position 306 (M306V). A novel mutation at codon 366 was identified (S366L) in one isolate. Ural was the most predominant genotype in the studied population. Beijing genotype was associated with both MDR and EMB resistance in which all mutations occurred at codon 306 of the embB gene.
  
  
  CONCLUSIONS
  A significant association between Beijing genotype and EMB resistance was found, mainly due to mutations at embB306. Results of this study can be used as a basis to develop or improve rapid molecular tests to monitor drug-resistant strains in this country.
authors.affiliation: School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. frezaei59@gmail.com.
authors.forename: Faranak
authors.initials: F
authors.lastname: Rezaei
authors.forename: Mehri
authors.initials: M
authors.lastname: Haeili
authors.forename: Parviz
authors.initials: P
authors.lastname: Mohajeri
authors.forename: Abdolrazagh
authors.initials: A
authors.lastname: Hashemi Shahraki
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Imani Fooladi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Zahednamazi
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Feizabadi
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial; D004977:Ethambutol / Q000494:pharmacology*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007492:Iran; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D010430:Pentosyltransferases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; C540269:EmbB protein, Mycobacterium tuberculosis; D010430:Pentosyltransferases