title: Riboswitch control of aminoglycoside antibiotic resistance.
abstract: 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.
authors: Key Laboratory of Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors: Xu
authors: X
authors: Jia
authors: Jing
authors: J
authors: Zhang
authors: Wenxia
authors: W
authors: Sun
authors: Weizhi
authors: W
authors: He
authors: Hengyi
authors: H
authors: Jiang
authors: Dongrong
authors: D
authors: Chen
authors: Alastair I H
authors: AI
authors: Murchie
mesh_terms: D020121:5' Untranslated Regions; D000123:Acetyltransferases / Q000235:genetics; D040981:Acinetobacter baumannii / Q000235:genetics; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics*; D001483:Base Sequence; D004926:Escherichia coli; D008780:Methyltransferases / Q000235:genetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009713:Nucleotidyltransferases / Q000235:genetics; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058928:Riboswitch
chemical_list: D020121:5' Untranslated Regions; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D058928:Riboswitch; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D009713:Nucleotidyltransferases; C020565:gentamicin 2''-nucleotidyltransferase