Multidrug-resistant
Mycobacterium tuberculosis infection is now world wide health problem. However, according to the recent advances of molecular
biological technics, some of the genetic mechanisms of drug-resistance of M.
tuberculosis has been uncovered. Generally, drug-resistance of M.
tuberculosis was caused by point mutations in chromosomal gene. In
isoniazid (INH) resistant M.
tuberculosis, mutations and genetic deletions in
catalase-
peroxidase gene (katG), inhA gene, or
alkyl hydroperoxide reductase gene were reported. We also found that about 15% of INH-resistant M.
tuberculosis isolates lacked katG gene, and these isolates showed highly resistance to INH with MIC > or = 64 micrograms/ml. On the other hand, mutations and other genetic alterations in
RNA polymerase beta subunit gene (rpoB) were the major mechanisms of resistance to
rifampicin (RFP) with high frequencies of 90% or more. Our evaluation of the relationship between RFP susceptibility and genetic alteration in rpoB gene also showed that 95% of RFP-resistant M.
tuberculosis isolates involved genetic alterations in 69 bp core region of rpoB gene. Moreover, these genetic alterations in rpoB gene were suspected as the resistant mechanism to other
rifamycin antituberculosis drugs, such as
rifabutin and
KRM-1648. In addition, it was reported that point mutations in
16S rRNA gene (rrs) and
ribosomal protein S12 gene (rpsL) induced M.
tuberculosis as
streptomycin (SM) resistant phenotype. We analyzed genetic alternations in rpsL gene of clinically isolates of M.
tuberculosis, about 60% of SM resistant isolates were shown point mutation in this gene ant they were all high SM-resistant with MIC > or = 256 micrograms/ml. Furthermore,
nicotinamidase (pncA) gene,
DNA gyrase A subunit (gyrA) gene, and embB gene were reported as the responsible gene to
pyrazinamide-,
quinolone- and
ethambutol-resistance, respectively. Although all mechanisms of drug-resistance were still unclear, these informations are very useful and helpful for development of rapid diagnosis system of
drug-resistant M.
tuberculosis.