Exclusive mutations related to isoniazid and ethionamide resistance among Mycobacterium tuberculosis isolates from Korea.
METHODS
The single base change at the 94th codon of inhA has been referred to as the event that confers resistance on the drugs isoniazid (INH) and ethionamide (ETH) in Mycobacterium smegmatis and M. bovis. From this observation, it has been anticipated that some of the INH-resistant clinical isolates of M. tuberculosis would carry missense mutations in the same region of the gene. However, few polymorphisms have been identified in this region among INH-resistant isolates.


OBJECTIVE
To understand the molecular basis for M. tuberculosis resistance to INH and ETH.


METHODS
The sequence polymorphism at the 94th codon of inhA among M. tuberculosis isolates from Korea was analyzed by polymerase chain reaction (PCR) cloning and sequence analysis.


RESULTS
No nucleotide change at the 94th codon of inhA was detected in any of the 24 INH-resistant isolates analyzed in this study. On the other hand, a point mutation was found exclusively at the regulatory region flanking a putative ribosome-binding site of the inhA locus in 14 isolates. Interestingly, all the mutations were of the same kind, which substitutes C to T. Among 14 isolates, 12 were resistant to INH as well as to ETH, while two were resistant to INH only.


CONCLUSIONS
It seems that mutations previously found at the 94th codon of inhA have no particular relationship with the mechanism involved in the resistance of M. tuberculosis to INH and/or ETH. On the other hand, the resistance mechanism of M. tuberculosis to INH/ETH may involve an altered level of InhA, an expression which may have been influenced by the sequence change in the regulatory region of the inhA locus.
Lee
H
H
Korean Institute of Tuberculosis, The Korean National Tuberculosis Association, Seoul.
Cho
S N
SN
Bang
H E
HE
Lee
J H
JH
Bai
G H
GH
Kim
S J
SJ
Kim
J D
JD
D000995:Antitubercular Agents / Q000494:pharmacology*; D001483:Base Sequence; D018432:Drug Resistance, Multiple; D005000:Ethionamide / Q000494:pharmacology*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D007723:Korea; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology*
D000995:Antitubercular Agents; D005000:Ethionamide; D007538:Isoniazid