title: Catalytic and structural properties of IRT-21 beta-lactamase (TEM-77) from a co-amoxiclav-resistant Proteus mirabilis isolate.
abstract: Proteus mirabilis strain MAG1, a clinical isolate that is resistant to broad-spectrum penicillins and co-amoxiclav, produces inhibitor-resistant TEM (IRT)-21, a novel mutant of TEM beta-lactamase. This enzyme has a pI of 5.2 and is derived from the bla(TEM-1a) gene ancestor. It contains two major amino acid substitutions specific for co-amoxiclav resistance (Leu-69 for Met and Ser-244 for Arg) that have never been found together previously. The dramatic loss of sensitivity to clavulanic acid, the enhancement of K(m) for all beta-lactams and markedly for ticarcillin, and the decrease in the catalytic efficiency makes IRT-21 comparable to the other IRTs with substitutions at position 244 or double substitutions.
authors.affiliation: Laboratoire de Bactériologie, CHU, Amiens, France.
authors.forename: H
authors.initials: H
authors.lastname: Mammeri
authors.forename: L
authors.initials: L
authors.lastname: Gilly
authors.forename: G
authors.initials: G
authors.lastname: Laurans
authors.forename: G
authors.initials: G
authors.lastname: Vedel
authors.forename: F
authors.initials: F
authors.lastname: Eb
authors.forename: G
authors.initials: G
authors.lastname: Paul
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D011513:Proteus mirabilis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination; C444921:IRT-21 beta-lactamase; D001618:beta-Lactamases