Acetylation of Amikacin, a New Semisynthetic Antibiotic, by Pseudomonas Aeruginosa Carrying an R Factor

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1975 Jan 1

PMID 806257

Citations 13

Authors

H Kawabe

T Naito

S Mitsuhashi

Affiliations

Soon will be listed here.

Abstract

A clinical isolate Pseudomonas aeruginosa GN315 resistant to amikacin (AK), a new semisynthetic antibiotic, inactivated AK by acetylation. The acetylating enzyme was purified approximately 146-fold from a crude extract of GN315 by affinity chromatography. Fractionated samples obtained by affinity chromatography showed almost the same inactivation curves toward 3',4'-dideoxykanamycin B (DKB) and AK. Partially purified AK-acetylating enzyme inactivated DKB and kanamycin A but could not inactivate gentamicin C(1). The optimal pH for their inactivation was 6.0 to 7.0, and the pH curves for the inactivation of both drugs were almost the same. These facts indicate that AK and DKB are inactivated by the same aminoglycoside-acetylating enzyme. Through elemental analysis, the inactivated AK was found to be a monoacetylated product of AK. A sample of inactivated AK was purified and compared with a synthetic 6'-N-acetyl AK by thin-layer chromatography, and the results indicated that AK was inactivated by acetylation of the 6'-NH(2) group. The ultraviolet, infrared, and nuclear magnetic resonance spectra of the inactivated AK showed that AK was inactivated by the enzyme through acetylation of the amino group of 6'-amino-6'-deoxy-d-glucose moiety of AK. This enzyme, mediated by R factor, is capable of conferring resistance to AK, DKB, kanamycin, gentamicin, and sulfanilamide.

Citing Articles

Amikacin: Uses, Resistance, and Prospects for Inhibition.

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Mapping of the gene specifying aminoglycoside 3'-phosphotransferase II on the Pseudomonas aeruginosa chromosome.

Okii M, Iyobe S, Mitsuhashi S J Bacteriol. 1983; 155(2):643-9.

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Transfer of amikacin resistance by closely related plasmids in members of the family Enterobacteriaceae isolated in Chile.

Van Nhieu G, Goldstein F, Pinto M, Acar J, Collatz E Antimicrob Agents Chemother. 1986; 29(5):833-7.

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Cloning and sequencing of a gene encoding an aminoglycoside 6'-N-acetyltransferase from an R factor of Citrobacter diversus.

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PMID: 2826403 PMC: 210671. DOI: 10.1128/jb.170.1.471-473.1988.

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