Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Antimicrob Agents Chemother. 2011 Jan;55(1):246-54. doi: 10.1128/AAC.00450-10. Epub 2010 Oct 18.
Gentamicin is a highly efficacious antibiotic against Gram-negative bacteria. However, its usefulness in treating infections is compromised by its poorly understood renal toxicity. Toxic effects are also seen in a variety of other organisms. While the yeast Saccharomyces cerevisiae is relatively insensitive to gentamicin, mutations in any one of ∼20 genes cause a dramatic decrease in resistance. Many of these genes encode proteins important for translation termination or specific protein-trafficking complexes. Subsequent inspection of the physical and genetic interactions of the remaining gentamicin-sensitive mutants revealed a network centered on chitin synthase and the Arf GTPases. Further analysis has demonstrated that some conditional arf1 and gea1 alleles make cells hypersensitive to gentamicin under permissive conditions. These results suggest that one consequence of gentamicin exposure is disruption of Arf-dependent protein trafficking.
庆大霉素是一种高效的抗革兰氏阴性菌抗生素。然而，其肾毒性机制尚未完全阐明，这限制了其在临床上的应用。该抗生素在多种其他生物体中也具有毒性作用。虽然酿酒酵母对庆大霉素相对不敏感，但任何一个约 20 个基因的突变都会导致其耐药性显著下降。这些基因中的许多编码蛋白质，对翻译终止或特定蛋白质运输复合物很重要。随后对剩余庆大霉素敏感突变体的物理和遗传相互作用进行检查，发现了一个以几丁质合酶和 Arf GTPases 为中心的网络。进一步的分析表明，一些条件性的 arf1 和 gea1 等位基因使细胞在允许条件下对庆大霉素变得高度敏感。这些结果表明，庆大霉素暴露的一个后果是破坏了 Arf 依赖的蛋白质运输。
