title: Riboswitch control of induction of aminoglycoside resistance acetyl and adenyl-transferases.
abstract: The acquisition of antibiotic resistance by human pathogens poses a significant threat to public health. The mechanisms that control the proliferation and expression of antibiotic resistance genes are not yet completely understood. The aminoglycosides are a historically important class of antibiotics that were introduced in the 1940s. Aminoglycoside resistance is conferred most commonly through enzymatic modification of the drug or enzymatic modification of the target rRNA through methylation or through the overexpression of efflux pumps. In our recent paper, we reported that expression of the aminoglycoside resistance genes encoding the aminoglycoside acetyl transferase (AAC) and aminoglycoside adenyl transferase (AAD) enzymes was controlled by an aminoglycoside-sensing riboswitch RNA. This riboswitch is embedded in the leader RNA of the aac/aad genes and is associated with the integron cassette system. The leader RNA can sense and bind specific aminoglycosides such that the binding causes a structural transition in the leader RNA, which leads to the induction of aminoglycoside antibiotic resistance. Specific aminoglycosides induce reporter gene expression mediated by the leader RNA. Aminoglycoside RNA binding was measured directly and, aminoglycoside-induced changes in RNA structure monitored by chemical probing. UV cross-linking and mutational analysis identified potential aminoglycoside binding sites on the RNA.
authors.affiliation: Key Laboratory of Molecular Medicine; the Ministry of Education; Department of Biochemistry and Molecular Biology; Fudan University Shanghai Medical College; Shanghai, PR China; Institutes of Biomedical Sciences; Fudan University Shanghai Medical College; Shanghai, PR China; School of Pharmacy; Fudan University; Pudong, Shanghai, China.
authors.forename: Weizhi
authors.initials: W
authors.lastname: He
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Jia
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Wenxia
authors.initials: W
authors.lastname: Sun
authors.forename: Hengyi
authors.initials: H
authors.lastname: Jiang
authors.forename: Dongrong
authors.initials: D
authors.lastname: Chen
authors.forename: Alastair I H
authors.initials: AI
authors.lastname: Murchie
mesh_terms: D020121:5' Untranslated Regions / Q000502:physiology*; D000123:Acetyltransferases / Q000378:metabolism*; D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D032023:Integrons; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009713:Nucleotidyltransferases / Q000378:metabolism*; D011551:Pseudomonas fluorescens / Q000235:genetics / Q000378:metabolism; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D058928:Riboswitch / Q000235:genetics / Q000502:physiology*
chemical_list: D020121:5' Untranslated Regions; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D058928:Riboswitch; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D009713:Nucleotidyltransferases
keywords: aminoglycoside; antibiotic resistance; antibiotic sensing RNA; induction of antibiotic resistance; integron; riboswitch