title: OXA-16, a further extended-spectrum variant of OXA-10 beta-lactamase, from two Pseudomonas aeruginosa isolates.
abstract: Two extended-spectrum mutants of the class D beta-lactamase OXA-10 (PSE-2) from Pseudomonas aeruginosa isolates obtained in Ankara, Turkey, were described previously and were designated OXA-11 and -14. P. aeruginosa 906 and 961, isolated at the same hospital, were highly resistant to ceftazidime (MIC >/= 128 microgram/ml) and produced a beta-lactamase with a pI of 6.2. The MICs of ceftriaxone, cefoperazone, cefsulodin, and cefepime were 4- to 16-fold above the typical values for P. aeruginosa, whereas the MICs of penicillins and cefotaxime were raised only marginally. Ceftazidime MICs were not significantly reduced by clavulanate or tazobactam at 4 microgram/ml. Ceftazidime resistance did not transfer conjugatively but was mobilized to P. aeruginosa PU21 by plasmid pUZ8. Both isolates gave similar DNA restriction patterns, suggesting that they were replicates; moreover, they yielded identically sized BamHI fragments that hybridized with a blaOXA-10 probe. DNA sequencing revealed that both isolates had the same new beta-lactamase, designated OXA-16, which differed from OXA-10 in having threonine instead of alanine at position 124 and aspartate instead of glycine at position 157. The latter change is also present in OXA-11 and -14 and seems critical to ceftazidime resistance. Kinetic parameters showed that OXA-16 enzyme was very active against penicillins, cephaloridine, cefotaxime, and ceftriaxone, but hydrolysis of ceftazidime was not detected despite the ability of the enzyme to confer resistance.
authors.affiliation: Antibiotic Group, Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, E1 2AD, United Kingdom. franck.danel@roche.com
authors.forename: F
authors.initials: F
authors.lastname: Danel
authors.forename: L M
authors.initials: LM
authors.lastname: Hall
authors.forename: D
authors.initials: D
authors.lastname: Gur
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001483:Base Sequence; D002442:Ceftazidime / Q000494:pharmacology; D018550:Cephalosporin Resistance / Q000235:genetics; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D001618:beta-Lactamases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime; C117195:beta-lactamase OXA-16; C055187:beta-lactamase PSE-2; D001618:beta-Lactamases