科研之友
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摘要
Resistance of Mycobacterium tuberculosis to ethambutol (ENS) 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 ENS-resistance of isolates whose minimum inhibitory concentration (MIC) level is higher than 20 mug/ml. On the contrary, isolates with a MIC level lower than 20 mug/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 ENS resistance, we investigated the sequence polymorphisms of clinical isolates whose MIC levels are lower than 10 mug/ml. Accordingly, the sequence alterations of a 312-bp region of the embB gene containing the 306(th) codon, which has been assigned as a hot-spot for ENM-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.
- 出版日期2002-2
