title: Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections.
abstract: Shortly after the discovery of the first antibiotics, bacterial resistance began to emerge. Many mechanisms give rise to resistance; the most prevalent mechanism of resistance to the aminoglycoside (AG) family of antibiotics is the action of aminoglycoside-modifying enzymes (AMEs). Since the identification of these modifying enzymes, many efforts have been put forth to prevent their damaging alterations of AGs. These diverse strategies are discussed within this review, including: creating new AGs that are unaffected by AMEs; developing inhibitors of AMEs to be co-delivered with AGs; or regulating AME expression. Modern high-throughput methods as well as drug combinations and repurposing are highlighted as recent drug-discovery efforts towards fighting the increasing antibiotic resistance crisis.
authors.affiliation: University of Kentucky, College of Pharmacy, Bio Pharm Complex, Room 423, Lexington, KY 40536-0596, USA.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Labby
authors.forename: Sylvie
authors.initials: S
authors.lastname: Garneau-Tsodikova
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019868:Kanamycin Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D019868:Kanamycin Kinase; D009713:Nucleotidyltransferases