title: In vivo and in vitro cross-resistance of kanamycin-resistant mutants of E. coli to other aminoglycoside antibiotics.
abstract: Cross resistance of kanamycin-resistant mutants of E. coli Q13 to other aminoglycosides (streptomycin, neomycin, gentamicin and dibekacin) was demonstrated in vivo (growth) and in vitro (polyphenylalanine synthesis, codon misreading and translocation on the ribosomes). Kanamycin-resistant mutants, R1-4, R2-1, R2-2, R3-3 and R3-5 showed various degrees of cross-resistance to streptomycin, gentamicin, neomycin and dibekacin in vivo. In vitro, polyphenylalanine synthesis was more resistant to kanamycin, streptomycin, neomycin and gentamicin on the ribosomes of the kanamycin-resistant mutants than on those of the parental strain. In the presence of kanamycin, neomycin or gentamicin, less degrees of [14C]isoleucine uptake with poly[U] (codon misreading) were observed on the ribosomes obtained from the resistant mutants than on the sensitive cell ribosomes. The N-acetyl-[14C]phenylalanyl-puromycin synthesis enhanced by an elongation factor, EF-G and GTP (translocation) was more resistant to kanamycin and dibekacin on the mutant ribosomes than on the parental ribosomes. The results indicate that the cross-resistance to other aminoglycoside antibiotics, as well as the kanamycin resistance, are attributed to mutational alterations of the ribosomes in these mutants.
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003062:Codon; D003429:Cross Reactions; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000254:growth & development*; D007612:Kanamycin / Q000494:pharmacology*; D009154:Mutation; D010452:Peptide Biosynthesis; D010455:Peptides; D010458:Peptidyl Transferases / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003062:Codon; D010455:Peptides; C012001:polyphenylalanine; D007612:Kanamycin; D012343:RNA, Transfer; D010458:Peptidyl Transferases