Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts.
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 Zn(2+) 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 (Mg(2+), Cr(3+), Cr(6+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), and Au(3+) 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.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA.
Yijia
Y
Li
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA.
Keith D
KD
Green
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA.
Brooke R
BR
Johnson
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA sylviegtsodikova@uky.edu.
Sylvie
S
Garneau-Tsodikova
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000201:enzymology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003001:Cloning, Molecular; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D016972:Enterobacter cloacae / Q000187:drug effects / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology; D008670:Metals / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D012492:Salts / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D008670:Metals; D012492:Salts; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D015032:Zinc