Abstract

Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as Mycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn2+ metal ions displayed an inhibitory effect on the resistance enzyme AAC(6')-Ib in Acinetobacter baumannii and Escherichia coli. In this study, we explore a wide array of metal salts (Mg2+, Cr3+, Cr6+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Au3+ with different counter ions) and their inhibitory effect on a large repertoire of AACs [AAC(2')-Ic, AAC(3)-Ia, AAC(3)-Ib, AAC(3)-IV, AAC(6')-Ib', AAC(6')-Ie, AAC(6')-IId, and Eis]. In addition, we determine the MIC values for amikacin and tobramycin in combination with a zinc pyrithione complex in clinical isolates of various bacterial strains (two strains of A. baumannii, three of Enterobacter cloacae, and four of Klebsiella pneumoniae) and one representative of each species purchased from the American Type Culture Collection.

Document Type

Article

Publication Date

7-2015

Notes/Citation Information

Published in Antimicrobial Agents and Chemotherapy, v. 59, no. 7, p. 4148-4156.

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The copyright holders have granted the permission for posting the article here.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1128/AAC.00885-15

Funding Information

This work was supported by startup funds from the College of Pharmacy at the University of Kentucky (S.G.-T.) and by National Institutes of Health grant AI090048 (S.G.-T.).

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