Document Report Card

ID: ALA1255425

Journal: Antimicrob Agents Chemother

Title: Mutant APH(2'')-IIa enzymes with increased activity against amikacin and isepamicin.

Authors: Toth M, Frase H, Chow JW, Smith C, Vakulenko SB.

Abstract: Directed evolution by random PCR mutagenesis of the gene for the aminoglycoside 2''-IIa phosphotransferase generated R92H/D268N and N196D/D268N mutant enzymes, resulting in elevated levels of resistance to amikacin and isepamicin but not to other aminoglycoside antibiotics. Increases in the activities of the mutant phosphotransferases for isepamicin are the result of decreases in K(m) values, while improved catalytic efficiency for amikacin is the result of both a decrease in K(m) values and an increase in turnover of the antibiotic. Enzymes with R92H, D268N, and D268N single amino acid substitutions did not result in elevated MICs for aminoglycosides.

CiteXplore: 20145089

DOI: 10.1128/aac.01444-09