Prospects for Circumventing Aminoglycoside Kinase Mediated Antibiotic Resistance
REVIEW ARTICLE published: 25 June 2013 CELLULAR AND INFECTION MICROBIOLOGY doi: 10.3389/fcimb.2013.00022 Prospects for circumventing aminoglycoside kinase mediated antibiotic resistance Kun Shi 1, Shane J. Caldwell 1, Desiree H. Fong 1* and Albert M. Berghuis 1,2* 1 Groupe de Recherche Axé sur la Structure des Protéines, Department of Biochemistry, McGill University, Montreal, QC, Canada 2 Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada Edited by: Aminoglycosides are a class of antibiotics with a broad spectrum of antimicrobial activity. Marcelo Tolmasky, California state Unfortunately, resistance in clinical isolates is pervasive, rendering many aminoglycosides University Fullerton, USA ineffective. The most widely disseminated means of resistance to this class of antibiotics Reviewed by: is inactivation of the drug by aminoglycoside-modifying enzymes (AMEs). There are two Sylvie Garneau-Tsodikova, University of Michigan, USA principal strategies to overcoming the effects of AMEs. The first approach involves the Maria S. Ramirez, IMPaM design of novel aminoglycosides that can evade modification. Although this strategy has (UBA-CONICET), Argentina yielded a number of superior aminoglycoside variants, their efficacy cannot be sustained in *Correspondence: the long term. The second approach entails the development of molecules that interfere Desiree H. Fong, Groupe de with the mechanism of AMEs such that the activity of aminoglycosides is preserved. Recherche Axé sur la Structure des Protéines, Department of Although such a molecule has yet to enter clinical development, the search for AME Biochemistry, McGill University, inhibitors has been greatly facilitated by the wealth of structural information amassed 3649 Promenade Sir William Osler, in recent years.
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