复旦大学上海医学院英国籍全职长江学者特聘教授、复旦大学生物医学研究院研究员Alastair Murchie和研究员陈东戎率领的课题组，历经3年多艰辛，终于在耐药性病原菌中首次发现了一种由氨基糖苷类抗生素药物调控的新型“核糖开关”，该“开关”对控制此类抗生素的“耐药性”有重大作用。
该成果符合开发新型靶标药物的要求，为人类最终攻克抗生素耐药这一世纪难题提供了全新视角和理论依据，具有极大的临床实用潜力。近日，最新一期世界顶级学术杂志《细胞》（《Cell》）以《新型氨基糖苷类抗生素核糖开关的发现》为题，刊发了这一重大发现。
随着人类抗生素的广泛应用，致病菌的耐药性增强，找到“耐药性如何形成的新机制”已成为各国科学家面临的共同“世纪难题”，而该课题组此次发现的由氨基糖苷类抗生素药物调控的新型“核糖开关”，有望攻克此难题。
最新研究证明，“核糖开关”是自然界细菌、高等植物体内天然存在的、有调控作用的传感器，位于细菌等体内特定的基因非编码区，它通过结合细菌等体内小分子代谢物来调控基因的表达，可以不依赖任何蛋白质因子而直接结合代谢物并发生结构变化，参与调控生物的基本代谢。这一调控机制一经发现，即刻引起各国科学家的高度关注。（生物谷Bioon.com）
doi:10.1016/j.cell.2012.12.019
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Riboswitch Control of Aminoglycoside Antibiotic Resistance
Xu Jia, Jing Zhang, Wenxia Sun, Weizhi He, Hengyi Jiang, Dongrong Chen, Alastair I.H. MurchieSee
Highlights
The 5′ leader RNA of aminoglycoside antibiotic-resistance genes is conserved
Aminoglycosides induce reporter gene expression by interacting with the leader RNA
The aminoglycosides bind to the leader RNA and induce a change in the RNA structure
Induction is independent of leader peptide stalling or drug-ribosome interactions
Summary
The majority of riboswitches are regulatory RNAs that regulate gene expression by binding small-molecule metabolites. Here we report the discovery of an aminoglycoside-binding riboswitch that is widely distributed among antibiotic-resistant bacterial pathogens. This riboswitch is present in the leader RNA of the resistance genes that encode the aminoglycoside acetyl transferase (AAC) and aminoglycoside adenyl transferase (AAD) enzymes that confer resistance to aminoglycoside antibiotics through modification of the drugs. We show that expression of the AAC and AAD resistance genes is regulated by aminoglycoside binding to a secondary structure in their 5′ leader RNA. Reporter gene expression, direct measurements of drug RNA binding, chemical probing, and UV crosslinking combined with mutational analysis demonstrate that the leader RNA functions as an aminoglycoside-sensing riboswitch in which drug binding to the leader RNA leads to the induction of aminoglycosides antibiotic resistance.
