title: Ribosomes of the extremely thermophilic eubacterium Thermotoga maritima are uniquely insensitive to the miscoding-inducing action of aminoglycoside antibiotics.
abstract: Poly(U)- and poly(UG)-programmed cell-free systems were developed from the extreme thermophilic, anaerobic eubacterium Thermotoga maritima, and their susceptibility to aminoglycoside and other antibiotics was assayed at a temperature (75 degrees C) close to the physiological optimum (80 degrees C) for cell growth and in vitro polypeptide synthesis, using a Bacillus stearothermophilus system as the reference. The synthetic capacity of the Thermotoga assay mixture was abolished by the eubacterium-targeted drugs chloramphenicol, thiostrepton, and kirromycin. However, streptomycin, the disubstituted 2-deoxystreptamines (kanamycin, gentamicin, neomycin, and paromomycin), and the monosubstituted 2-deoxystreptamine (hygromycin) all failed to promote translational misreading of poly(U) on Thermotoga ribosomes; they also failed to block polyphenylalanine synthesis at a low (less than 10(-4) M) concentration and did not inhibit Thermotoga cell growth at a high (10 micrograms/ml) concentration even though Thermotoga ribosomes possess the 16S rRNA sequences required for aminoglycoside action. In contrast to the other eubacteria, Thermotoga elongation factor G was also refractory to the steroid inhibitor of peptidyl-tRNA translocation fusidic acid.
authors.affiliation: Dipartimento di Biopatologia Umana, Universitá di Roma I, Policlinico Umberto I, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Londei
authors.forename: S
authors.initials: S
authors.lastname: Altamura
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: K O
authors.initials: KO
authors.lastname: Stetter
authors.forename: P
authors.initials: P
authors.lastname: Cammarano
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006089:Gram-Negative Anaerobic Bacteria / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000648:ultrastructure; D006358:Hot Temperature; D010452:Peptide Biosynthesis; D010649:Phenylalanine / Q000096:biosynthesis; D014176:Protein Biosynthesis; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D010649:Phenylalanine