Antibiotic susceptibility of mammalian mitochondrial translation.
All medically useful antibiotics should have the potential to distinguish between target microbes (bacteria) and host cells. Although many antibiotics that target bacterial protein synthesis show little effect on the translation machinery of the eukaryotic cytoplasm, it is unclear whether these antibiotics target or not the mitochondrial translation machinery. We employed an in vitro translation system from bovine mitochondria, which consists of mitochondrial ribosomes and mitochondrial elongation factors, to estimate the effect of antibiotics on mitichondrial protein synthesis. Tetracycline and thiostrepton showed similar inhibitory effects on both Escherichia coli and mitochondrial protein synthesis. The mitochondrial system was more resistant to tiamulin, macrolides, virginiamycin, fusidic acid and kirromycin than the E. coli system. The present results, taken together with atomic structure of the ribosome, may provide useful information for the rational design of new antibiotics having less adverse effects in humans and animals.
Zhang
Li
L
Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Ging
Ng Ching
NC
Komoda
Taeko
T
Hanada
Takao
T
Suzuki
Tsutomu
T
Watanabe
Kimitsuna
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002417:Cattle; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010445:Peptide Elongation Factors / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D012270:Ribosomes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010445:Peptide Elongation Factors