[Study on the molecular mechanism of multi-drug resistance in clinical isolates of Mycobacterium tuberculosis].
OBJECTIVE
To study the molecular mechanism of multi-drug resistance in M. Tuberculosis, and to develop a new method for detecting genes related with multi-drug resistance.


METHODS
The ropB, rpsL, katG genes and inhA regulatory sequence in clinical isolates of M. tuberculosis were analyzed with PCR and PCR-SSCP techniques.


RESULTS
The sensitivity of amplifing the drug-resistant genes with PCR was 1-10 pg DNA. Of the 20 multiple resistant strains with reduced sensitivity to streptomycin, rifampin and isoniazid, 90% showed mutations in more than two genetic markers associated with resistance to each of these three drugs, 10% revealed only mutations in rpoB gene.


CONCLUSIONS
Multi-drug resistance in M. tuberculosis could be caused by an accumulation of mutations in chromosomal genes encoding drug targets or an alteration at a single multiple resistance locus. PCR and PCR-SSCP techniques might become simple, rapid and reliable diagnostic tests for multi-drug resistance.
Wu
X
X
Tuberculosis Research Laboratory, 309th Hospital, P.L.A., Beijing.
Zhuang
Y
Y
Zhang
J
J
D000995:Antitubercular Agents / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005798:Genes, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012293:Rifampin / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin