title: Correlation of the phenotypic ethambutol susceptibility of Mycobacterium tuberculosis with embB gene mutations in Korea.
abstract: The phenotypic resistance to ethambutol (EMB) in Mycobacterium tuberculosis with embB gene mutations is still unclear. This study was designed to better understand EMB resistance due to embB gene mutation. Sequencing analysis of the embB gene was performed for 124 EMB-susceptible and 93 EMB-resistant M. tuberculosis strains isolated from South Korea. The MIC was determined for EMB-susceptible M. tuberculosis strains with the embB mutation and wild-type on Löwenstein-Jenson (LJ) solid medium in duplicate. Two (2.8 %) of 72 pan-susceptible, two (9.1 %) of 22 any-drug-resistant but EMB-susceptible, nine (30.0 %) of 30 multidrug-resistant (MDR) but EMB-susceptible and 84 (90.3 %) of 93 EMB-resistant M. tuberculosis strains possessed embB mutations at various codons including 306, 319, 354, 360, 399, 405, 406, 459 and 497. Strains with embB mutations at codons 306, 354, 399, 405 and 497 had highly pronounced EMB resistance, while strains with mutations at codons 319 and 406 mutations were moderately resistant and those with an embB459 mutation were EMB-susceptible at the critical concentration (2.0 µg ml(-1)) on LJ solid medium. However, the mean MIC for strains with embB mutations (1.42 µg ml(-1)) was higher than that for strains without the embB mutation (1.0 µg ml(-1)) in EMB-susceptible M. tuberculosis isolates (P = 0.0052). Three novel embB mutations at codons 399, 405 and 459 were identified in this study. These results support the hypothesis that embB mutation except for a few specific mutation types may be the main cause of EMB resistance.
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Young Kil
authors.initials: YK
authors.lastname: Park
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Sung Weon
authors.initials: SW
authors.lastname: Ryoo
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Hum Nath
authors.initials: HN
authors.lastname: Jnawali
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Kim
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Korean Institute of Tuberculosis, 482 Mansuri, Kangwoimyun, Cheongwongun, Chungbuk, Republic of Korea.
authors.forename: Sang Jae
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004977:Ethambutol / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D010430:Pentosyltransferases / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; C540269:EmbB protein, Mycobacterium tuberculosis; D010430:Pentosyltransferases