抗酸菌における交叉耐性--遺伝学的,生化学的考察

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It has been known that cross resistance relationships among aminoglycoside and peptide antibiotics in mycobacteria are very much complicated depending on the different authors and mutants used in the investigations. In this review, discussions were made on the possible nature of the complexity of mycobacterial cross resistance. From biochemical point of view, mechanisms of drug resistance can be classified into two categories. One is governed by R plasmid, and the resistance to the antibiotics were due to inactivation of the drugs by enzymes. In this case, cross resistances were determined by substrate specificity of the enzymes. For instance, drug resistance pattern of a cell having an enzyme amino-glycoside-3'-phosphotransferase I is different from that having aminoglycoside-3'-phosphotransferase II. There have been no reports on the presence of R plasmid in mycobacteria. Recently, however, a strain of M. tuberculosis having kanamycin acetylating enzyme has been isolat ed. Possibly, at least some of the drug resistant clinical isolates have R plasmids in their cytoplasm. Most of the resistant mycobacteria isolated in the laboratory and perhaps some of the clinical isolates also, have altered ribosomes. Mutants with altered ribosomal components often show cross resistance of various phenotypes. For instance, mutation in vicA gene which determines a component of 50 S ribosomal subunits, confers resistance to viomycin and capreomycin but does not show cross resistance to kanamycin. On the contrary, mutation in vicB gene which is a structural gene for 30 S ribosomal subunits, confers resistance to viomycin, capreomycin and show weak cross resistance to kanamycin.There are evidences of functional co-operation between different ribosomal components. Forinstance, the levels of resistance to viomycin due to a change in 50 S ribosomal com ponent greatly increased when streptomycin resistant mutation was introduced into the strain. Such a functional co-operation also makes cross resistance complicated.
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抗酸菌における交叉耐性--遺伝学的,生化学的考察

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