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 language | English |
|---|---|
| Pages (from-to) | 59-64 |
| Number of pages | 6 |
| Journal | Yonsei medical journal |
| Volume | 43 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2002 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Medicine(all)
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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 journal › Article
TY - JOUR
T1 - Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol
AU - Lee, Hyeyoung
AU - Myoung, Han Jung
AU - Bang, Hye Eun
AU - Bai, Gill Han
AU - Kim, Sang Jae
AU - Kim, Joo Deuk
AU - Cho, Sang Nae
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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.
AB - 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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U2 - 10.3349/ymj.2002.43.1.59
DO - 10.3349/ymj.2002.43.1.59
M3 - Article
C2 - 11854934
AN - SCOPUS:0036184886
VL - 43
SP - 59
EP - 64
JO - Yonsei Medical Journal
JF - Yonsei Medical Journal
SN - 0513-5796
IS - 1
ER -