Mutational studies of the drug-resistance of M. tuberculosis with special reference to p-aminosalicylic acid, ethambutol, isoniazid and rifampicin.
In the M. tuberculosis H37Rv and in the human tubercular strains isolated from patients, the localization of genetic determinants of drug-resistance to antitubercular chemotherapeutic drugs in current use was studied. Data obtained through the treatment of the resistanct strains with acridine dyes and ethidium bromide, and the analysis of irreversible elimination of resistance markers support the hypothesis of an extrachromosomal locus for the p-aminosalicylic acid (PAS)-resistance and confirm a chromosomal mutation for the isoniazid (INH), ethambutol (EM), rifampicin (R/AMP)-resistances, in all the levels reached in training or selected in wild strains. In the PAS-revertants recovered after treatment with mutagenic agents, a loss by degrees of resistance levels was observed. In a mycobacterial strain biresistant to PAS and streptomycin (Sm) the Authors were able to find a loss of the mono-resistance to Sm only. The significance of these results is discussed in terms of plasmid (s) having separate mutational loci for PAS- and for the aminoglycoside-resistance. These results agree with the previous studies in the field of resistance of Mycobacteria to specific drugs.
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005111:Extrachromosomal Inheritance / Q000187:drug effects; D007538:Isoniazid / Q000494:pharmacology*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D007538:Isoniazid; D012293:Rifampin