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Antimicrob Agents Chemother. 1975 January; 7(1): 50-54
Copyright © 1975 American Society for Microbiology. All Rights Reserved.

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

Haruhide Kawabe*, Takayuki Naito and Susumu Mitsuhashi

* Department of Microbiology, School of Medicine, Gunma University, Maebashi
Bristol-Banyu Research Institute Ltd., Tokyo, Japan

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 C1. 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'-NH2 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.


Antimicrob Agents Chemother. 1975 January; 7(1): 50-54
Copyright © 1975 American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Wingfield, D. L., McDougal, R. L., Roy, F. H., Hanna, C. (1983). Ocular Penetration of Amikacin Following Intramuscular Injection. Arch Ophthalmol 101: 117-120 [Abstract]  
  • Sklaver, A. R., Greenman, R. L., Hoffman, T. A. (1978). Amikacin Therapy of Gram-Negative Bacteremia and Meningitis: Treatment in Diseases Due to Multiple Resistant Bacilli. Arch Intern Med 138: 713-716 [Abstract]  
  • MEYER, R. D., LEWIS, R. P., CARMALT, E. D., FINEGOLD, S. M. (1975). Amikacin Therapy for Serious Gram-Negative Bacillary Infections. ANN INTERN MED 83: 790-800 [Abstract]