Genetic and biochemical characterization of the first extended-spectrum CARB-type beta-lactamase, RTG-4, from Acinetobacter baumannii.
Acinetobacter baumannii isolate KAR was uncommonly more resistant to cefepime and cefpirome than to ceftazidime and cefotaxime. Cloning and expression of the beta-lactamase gene content of this isolate into Escherichia coli TOP10 identified ss-lactamase RTG-4 (or CARB-10), which corresponds to the first reported extended-spectrum CARB-type enzyme. RTG-4 is a plasmid-encoded Ambler class A beta-lactamase whose sequence differs by 4 amino acid substitutions from the narrow-spectrum beta-lactamase RTG-3. RTG-4 hydrolyzes cefepime and cefpirome and weakly hydrolyzes ceftazidime due to the single Ser-to-Thr substitution at Ambler position 69. RTG-4 is less susceptible to inhibition by tazobactam and sulbactam than RTG-3. Expression of beta-lactamase RTG-4 in a wild-type A. baumannii reference strain showed that it conferred resistance to cefepime and cefpirome. The genetic environment of the bla(RTG-4) gene was made of a peculiar transposon located on a ca. 50-kb plasmid. ISAba9, located upstream of bla(RTG-4), may be responsible for its acquisition by recognizing a secondary right inverted repeat sequence, thus acting by a one-ended transposition process.
Potron
Anaïs
A
Service de Bactériologie-Virologie-Hygiène, Hôpital de Bicêtre, Faculté de Médecine et Université Paris-Sud, 78 rue de Général Leclerc, Le Kremlin-Bicêtre Cedex 94275, France.
Poirel
Laurent
L
Croizé
Jacques
J
Chanteperdrix
Vanessa
V
Nordmann
Patrice
P
D040981:Acinetobacter baumannii / Q000201:enzymology*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001618:beta-Lactamases