Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol

Hyeyoung Lee, Han Jung Myoung, Hye Eun Bang, Gill Han Bai, Sang Jae Kim, Joo Deuk Kim, Sang Nae Cho

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Abstract

Resistance of Mycobacterium tuberculosis to ethambutol (EMB) has been assigned to an operon, embCAB, which has been proposed to be a structural gene for mycobacterial arabinosyl transferases. Recently, genetic events resulting in structural mutations at embB have been proposed as major contributors to the EMB-resistance of isolates whose minimum inhibitory concentration (MIC) level is higher than 20 μ g/ml. On the contrary, isolates with a MIC level lower than 20 μ g/ml do not seem to contain any sequence alterations. In this study, in an effort to understand the role of embB mutations at a low-level of EMB resistance, we investigated the sequence polymorphisms of clinical isolates whose MIC levels are lower than 10 μg/ml. Accordingly, the sequence alterations of a 312-bp region of the embB gene containing the 306th codon, which has been assigned as a hot-spot for EMB-resistance related mutations, were determined for 21 EMB-resistant and 5 EMB-susceptible clinical isolates. In brief, among 21 EMB-resistant isolates examined, 12 (57.1%) contained mutations in embB (10 at the 306th codon and 2 at other sites), and the remaining isolates 9 contained no mutations in any region of embB. The observed mutations included M306V, M306I, and M306L substitutions that have been reported previously. However, 3 were novel types, which included M306T, A313G and Y322C, D331Y double substitutions. On the other hand, all of the EMB-susceptible isolates were found to be free of mutations. In conclusion, our findings suggest that sequence polymorphism of embB may play a pivotal role in the EMB-resistance of M. tuberculosis.

Original languageEnglish
Pages (from-to)59-64
Number of pages6
JournalYonsei medical journal
Volume43
Issue number1
DOIs
Publication statusPublished - 2002 Jan 1

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Ethambutol
Mycobacterium tuberculosis
Mutation
Microbial Sensitivity Tests
Codon
Operon
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lee, Hyeyoung ; Myoung, Han Jung ; Bang, Hye Eun ; Bai, Gill Han ; Kim, Sang Jae ; Kim, Joo Deuk ; Cho, Sang Nae. / Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol. In: Yonsei medical journal. 2002 ; Vol. 43, No. 1. pp. 59-64.
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abstract = "Resistance of Mycobacterium tuberculosis to ethambutol (EMB) has been assigned to an operon, embCAB, which has been proposed to be a structural gene for mycobacterial arabinosyl transferases. Recently, genetic events resulting in structural mutations at embB have been proposed as major contributors to the EMB-resistance of isolates whose minimum inhibitory concentration (MIC) level is higher than 20 μ g/ml. On the contrary, isolates with a MIC level lower than 20 μ g/ml do not seem to contain any sequence alterations. In this study, in an effort to understand the role of embB mutations at a low-level of EMB resistance, we investigated the sequence polymorphisms of clinical isolates whose MIC levels are lower than 10 μg/ml. Accordingly, the sequence alterations of a 312-bp region of the embB gene containing the 306th codon, which has been assigned as a hot-spot for EMB-resistance related mutations, were determined for 21 EMB-resistant and 5 EMB-susceptible clinical isolates. In brief, among 21 EMB-resistant isolates examined, 12 (57.1{\%}) contained mutations in embB (10 at the 306th codon and 2 at other sites), and the remaining isolates 9 contained no mutations in any region of embB. The observed mutations included M306V, M306I, and M306L substitutions that have been reported previously. However, 3 were novel types, which included M306T, A313G and Y322C, D331Y double substitutions. On the other hand, all of the EMB-susceptible isolates were found to be free of mutations. In conclusion, our findings suggest that sequence polymorphism of embB may play a pivotal role in the EMB-resistance of M. tuberculosis.",
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Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol. / Lee, Hyeyoung; Myoung, Han Jung; Bang, Hye Eun; Bai, Gill Han; Kim, Sang Jae; Kim, Joo Deuk; Cho, Sang Nae.

In: Yonsei medical journal, Vol. 43, No. 1, 01.01.2002, p. 59-64.

Research output: Contribution to journalArticle

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