[Molecular mechanisms of multidrug resistance in Mycobacterium tuberculosis].
Control of tuberculosis caused by multidrug-resistant (MDR) Mycobacterium (M.) tuberculosis has become one of the major problems throughout the world. Understanding of the molecular mechanisms of resistance may help in the development of novel methods for the rapid and precise detection of drug-resistant M. tuberculosis. Eight agents have been recommended to treat tuberculosis. Isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA), streptomycin(SM), and ethambutol (EB) are used as the first line agents, and the others are the second line agents. MDR M. tuberculosis strains are resistant both to INH and RFP which have the most effective bactericidal activity to M. tuberculosis. Nearly 95% of RFP resistant strains possess a mutation on the rpoB gene encoding a DNA-dependent RNA polymerase. INH particularly shows an inhibition of the cell wall synthesis of M. tuberculosis and approximately 90% of INH resistant strains have a mutation on the inhA, katG, and ahpG gene encoding enzymes related to a mycolic acid synthesis of cell wall. PZA resistant strains have a mutation on the pncA gene encoding a pyrazinamidase which degradates pyrazinamide to a bactericidal substance, pyrazinoic acid. SM resistant strains have a mutation on the rrs and rpsL gene encoding a 16S rRNA and a S12 ribosomal subunit protein, respectively. EB resistant strains have a mutation on the embB gene encoding a arabinosyl transferase which catalyzes cell wall synthesis. Resistant mechanisms of second-line agents have also been identified. Recently, rapid detection methods for RFP and INH resistant mutations have been developed on the basis of these studies.
Taniguchi
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Department of Microbiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
D000995:Antitubercular Agents / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004977:Ethambutol / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D011718:Pyrazinamide / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin