| Abstrakt: |
ABSTRACTThe effects of mutations in host genes on tetracycline resistance mediated by the Tet(O) and Tet(M) ribosomal protection proteins, which originated in Campylobacterspp. andStreptococcusspp., respectively, were investigated by using mutants of Salmonella typhimuriumand Escherichia coli. The miaA,miaB, and miaABdouble mutants of S. typhimuriumspecify enzymes for tRNA modification at the adenosine at position 37, adjacent to the anticodon in tRNA. InS. typhimurium, this involves biosynthesis ofN6-(4-hydroxyisopentenyl)-2-methylthioadenosine (ms2io6A). The miaAmutation reduced the level of tetracycline resistance mediated by both Tet(O) and Tet(M), but the latter showed a greater effect, which was ascribed to the isopentenyl (i6) group or to a combination of the methylthioadenosine (ms2) and i6groups but not to the ms2group alone (specified by miaB). In addition, mutations in E. coli rpsLgenes, generating both streptomycin-resistant and streptomycin-dependent strains, were also shown to reduce the level of tetracycline resistance mediated by Tet(O) and Tet(M). The single-site amino acid substitutions present in the rpsLmutations were pleiotropic in their effects on tetracycline MICs. These mutants affect translational accuracy and kinetics and suggest that Tet(O) and Tet(M) binding to the ribosome may be reduced or slowed in theE. coli rpsLmutants in which the S12 protein is altered. Data from both the miaAand rpsLmutant studies indicate a possible link between stability of the aminoacyl-tRNA in the ribosomal acceptor site and tetracycline resistance mediated by the ribosomal protection proteins. |
