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Antimicrobial Agents and Chemotherapy, June 1999, p. 1362-1366, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

OXA-17, a Further Extended-Spectrum Variant of OXA-10 beta -Lactamase, Isolated from Pseudomonas aeruginosa

Franck Danel,1,* Lucinda M. C. Hall,1 Brigid Duke,1 Deniz Gur,2 and David M. Livermore1,dagger

Antibiotic Group, Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, E1 2AD, United Kingdom,1 and Section of Infectious Diseases, Department of Internal Medicine, Hacettepe University School of Medicine, 06100 Ankara, Turkey2

Received 16 June 1998/Returned for modification 24 November 1998/Accepted 12 March 1999

Pseudomonas aeruginosa isolates 871 and 873 were isolated at Hacettepe University Hospital in Ankara and were highly resistant to ceftazidime (MIC, 128 µg/ml). Each produced three beta -lactamases, with pIs of 5.3, 6.1, and 7.9. The beta -lactamase with a pI of 5.3 was previously shown to be PER-1 enzyme. The antibiograms of the isolates were not entirely explained by production of PER-1 enzyme, insofar as ceftazidime resistance was incompletely reversed by clavulanate. The enzymes with pIs of 6.1 and 7.9 were therefore investigated. The enzyme with a pI of 6.1 proved to be a novel mutant of OXA-10, which we designated OXA-17, and had asparagine changed to serine at position 73 of the protein. When cloned into Escherichia coli XL1-blue, OXA-17 enzyme conferred greater resistance to cefotaxime, latamoxef, and cefepime than did OXA-10, but it had only a marginal (two- to fourfold) effect on the MIC of ceftazidime. This behavior contrasted with that of previous OXA-10 mutants, specifically OXA-11, -14, and -16, which predominately compromise ceftazidime. Extracted OXA-17 enzyme had relatively greater activity than OXA-10 against oxacillin, cloxacillin, and cefotaxime but, in terms of kcat/Km, it had lower catalytic efficiency against most beta -lactams. The enzyme with a pI of 7.9 was shown by gene sequencing to be OXA-2.


* Corresponding author. Present address: Pharmaceuticals Division, Pharma Research Preclinical Infectious Disease, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. Phone: 41-61-6880537. Fax: 41-61-6882729. E-mail: franck.danel{at}roche.com.

dagger Present address: Antibiotic Reference Unit, Laboratory of Hospital Infection, Central Public Health Laboratory, London, NW9 5HT, United Kingdom.


Antimicrobial Agents and Chemotherapy, June 1999, p. 1362-1366, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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