Novel OXA-10-derived extended-spectrum beta-lactamases selected in vivo or in vitro.
A clinical isolate of Pseudomonas aeruginosa, PAe191, was found to be highly resistant to all anti-Pseudomonas beta-lactam antibiotics (except imipenem) and resistant also to aminoglycosides. It produced a beta-lactamase (with an apparent pI of 7.6) which was not inhibited by clavulanic acid. Cloning and characterization of the beta-lactamase gene showed that it coded for a novel extended-spectrum OXA-10 variant, called OXA-19, which differed from OXA-10 by nine amino acids and from OXA-13 by two, i.e., Asn in position 73 (Asn73) instead of Ser and Asp157 instead of Gly. Asparagine in position 157 is implicated in resistance to ceftazidime, while the amino acid in position 73, in this variant, seems to condition the level of resistance to penicillins. The oxa19 gene was found to be inserted, in a typical integron structure, immediately downstream from an aac(6')-Ib gene coding for an aminoglycoside acetyltransferase variant, which was called AAC(6')-Ib9.
Mugnier
P
P
Laboratoire de Recherche Moléculaire sur les Antibiotiques, UFR Broussais-Hôtel Dieu and UFR Pitié-Salpêtrière, Université Paris VI.
Casin
I
I
Bouthors
A T
AT
Collatz
E
E
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000302:isolation & purification; D001618:beta-Lactamases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; C112402:beta-lactamase OXA-13; C117194:beta-lactamase OXA-19; C055187:beta-lactamase PSE-2; D001618:beta-Lactamases