Yonsei Med J.  2002 Feb;43(1):59-64. 10.3349/ymj.2002.43.1.59.

Mutations in the embB Locus among Korean Clinical Isolates of Mycobacterium tuberculosis Resistant to Ethambutol

• Lee HY
• Myoung HJ
• Bang HE
• Bai GH
• Kim SJ
• Kim JD
• Cho SN

• KMID: 1726069
• DOI: http://doi.org/10.3349/ymj.2002.43.1.59

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.

Keyword

M. tuberculosis; ethambutol resistance; embB mutations

MeSH Terms

Antitubercular Agents/*pharmacology
Chromosome Mapping
Drug Resistance, Bacterial
Ethambutol/*pharmacology
*Mutation
Mycobacterium tuberculosis/*drug effects/genetics
Pentosyltransferases/*genetics
Polymerase Chain Reaction