Fe-S Cluster Biosynthesis Controls Uptake of Aminoglycosides in a ROS-Less Death Pathway
Fe-S Cluster Biosynthesis Controls Uptake of Aminoglycosides in a ROS-Less Death Pathway
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DOI：
10.1126/science.1238328
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发表时间：
2013-06-28
期刊：
影响因子：
56.9
通讯作者：
Barras, Frederic
中科院分区：
文献类型：
--
作者：
Ezraty, Benjamin;Vergnes, Alexandra;Barras, Frederic
最近提出的所有杀菌抗生素都是通过诱导活性氧簇(ROS)的产生，导致铁-硫簇(Fe-S)的不稳定和产生芬顿化学来杀死细菌的。我们发现，使用杀菌抗生素治疗时，ROS反应是可有可无的。此外，我们还证明了只有氨基糖苷类药物才需要铁-S簇。与细胞不同，使用主要的铁-S簇生物合成机制的细胞，使用替代机制SuF的细胞，不能有效地成熟呼吸复合体I和II，导致质子动力(PMF)的阻抗，这是杀菌剂氨基糖苷类摄取所必需的。类似地，在铁限制期间，细胞通过从ISC转换为SuF并下调两个呼吸复合体而对氨基糖苷类药物产生固有的抵抗力。我们的结论是，铁-S蛋白通过使其被摄取来促进氨基糖苷类药物的杀伤。
All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing destabilization of iron-sulfur (Fe-S) clusters and generating Fenton chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake.