Unique antibiotic sensitivity of archaebacterial polypeptide elongation factors.
The antibiotic sensitivity of the archaebacterial factors catalyzing the binding of aminoacyl-tRNA to ribosomes (elongation factor Tu [EF-Tu] for eubacteria and elongation factor 1 [EF1] for eucaryotes) and the translocation of peptidyl-tRNA (elongation factor G [EF-G] for eubacteria and elongation factor 2 [EF2] for eucaryotes) was investigated by using two EF-Tu and EF1 [EF-Tu(EF1)]-targeted drugs, kirromycin and pulvomycin, and the EF-G and EF2 [EF-G(EF2)]-targeted drug fusidic acid. The interaction of the inhibitors with the target factors was monitored by using polyphenylalanine-synthesizing cell-free systems. A survey of methanogenic, halophilic, and sulfur-dependent archaebacteria showed that elongation factors of organisms belonging to the methanogenic-halophilic and sulfur-dependent branches of the "third kingdom" exhibit different antibiotic sensitivity spectra. Namely, the methanobacterial-halobacterial EF-Tu(EF1)-equivalent protein was found to be sensitive to pulvomycin but insensitive to kirromycin, whereas the methanobacterial-halobacterial EF-G(EF2)-equivalent protein was found to be sensitive to fusidic acid. By contrast, sulfur-dependent thermophiles were unaffected by all three antibiotics, with two exceptions; Thermococcus celer, whose EF-Tu(EF1)-equivalent factor was blocked by pulvomycin, and Thermoproteus tenax, whose EF-G(EF2)-equivalent factor was sensitive to fusidic acid. On the whole, the results revealed a remarkable intralineage heterogeneity of elongation factors not encountered within each of the two reference (eubacterial and eucaryotic) kingdoms.
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001105:Archaea / Q000187:drug effects* / Q000378:metabolism; D001419:Bacteria / Q000187:drug effects*; D019605:Euryarchaeota / Q000187:drug effects / Q000378:metabolism; D005672:Fusidic Acid / Q000494:pharmacology; D006027:Glycosides / Q000494:pharmacology; D006217:Halobacterium / Q000187:drug effects / Q000378:metabolism; D010444:Peptide Elongation Factor Tu / Q000037:antagonists & inhibitors; D010445:Peptide Elongation Factors / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000494:pharmacology; D013045:Species Specificity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D006027:Glycosides; D010445:Peptide Elongation Factors; D011728:Pyridones; C012521:pulvomycin; D005672:Fusidic Acid; D010444:Peptide Elongation Factor Tu; C008536:mocimycin