Mutations in the embB Locus among Korean Clinical Isolates of Mycobacterium tuberculosis Resistant to Ethambutol .
- Author:
Hye Young LEE
1
;
Han Jung MYOUNG
;
Hye Eun BANG
;
Gill Han BAI
;
Sang Jae KIM
;
Joo Deuk KIM
;
Sang Nae CHO
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: M. tuberculosis; ethambutol resistance; embB mutations
- MeSH: Antitubercular Agents/*pharmacology; Chromosome Mapping; Drug Resistance, Bacterial; Ethambutol/*pharmacology; *Mutation; Mycobacterium tuberculosis/*drug effects/genetics; Pentosyltransferases/*genetics; Polymerase Chain Reaction
- From:Yonsei Medical Journal 2002;43(1):59-64
- CountryRepublic of Korea
- Language:English
- 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 microgram/ml. On the contrary, isolates with a MIC level lower than 20 microgram/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 microgram/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.
