Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections

Author:

Labby Kristin J1,Garneau-Tsodikova Sylvie2

Affiliation:

1. Associate Professor of Pharmaceutical Sciences, University of Kentucky, College of Pharmacy, Bio Pharm Complex, Room 423, Lexington, KY 40536-0596, USA

2. Associate Professor of Pharmaceutical Sciences, University of Kentucky, College of Pharmacy, Bio Pharm Complex, Room 423, Lexington, KY 40536-0596, USA.

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.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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