Journal of Antimicrobial Chemotherapy (1999) 43, 339-344
© 1999 The British Society for Antimicrobial Chemotherapy
Laboratory mutants of OXA-10 ß-lactamase giving ceftazidime resistance in Pseudomonas aeruginosa
Antibiotic Group, Department of Medical Microbiology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, UK
Several extended-spectrum ß-lactamases (ESBLs) belonging to molecular Class D have been described from Pseudomonas aeruginosa isolates collected in Turkey. Four of these, OXA-11, -14, -16 and -17, are derivatives of OXA-10 -lactamase. We tried to select similar mutants in vitro from OXA-10-producing transconjugants of P. aeruginosa, using a multistep method on ceftazidime-containing agars. Forty-four such mutants were obtained; all had increased resistance to ceftriaxone, cefsulodin, cefepime, cefpirome, latamoxef, aztreonam and, especially, ceftazidime whereas MICs of piperacillin, carbenicillin, cefotaxime, cefoperazone and carbapenems were little altered. Genes related to bla OXA-10 were sequenced from five mutants. One mutant enzyme had aspartate instead of glycine at position 157, and corresponded exactly to natural OXA-14 ß-lactamase. Another mutant strain appeared to have both OXA-14 and a new pI 6.2 enzyme, designated OXA-M102, with serine instead of alanine at position 124 and aspartate instead of glycine at position 157. This latter variant resembled natural OXA-16 enzyme, which has threonine at position 124 and aspartate at position 157. The remaining three mutant enzymes differed from any so far found in wild-type isolates. Two had leucine replacing tryptophan at position 154 (this enzyme was named OXA-M101) while the third (OXA-M103) had a pI of 7.6, and had lysine instead of asparagine at position 143. A different mutation at this position was previously found in OXA-11, a wild-type OXA-10 mutant. Thus, some of the ESBL mutants selected (OXA-14 and OXA-M102) correspond exactly or almost exactly to ESBLs found in wild-types, whereas others (OXA-M101 and OXA-M103) were totally new.
* Present address: F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Pharma Research Preclinical Infectious Disease, CH-4070 Basel, Switzerland. Tel: +41-61-6880537; Fax: +41-61-6882729; E-mail: franck.danel{at}roche.com
Present address: Antibiotic Reference Unit, Laboratory of Hospital
Infection, Central Public Health Laboratory, 61 Colindale Avenue, London NW9 5HT, UK.
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