Reference : GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from pseudomonas aeruginosa...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/143573
GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from pseudomonas aeruginosa that contains Ile80 and Ser170 residues.
English
Bebrone, Carine mailto [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Bogaerts, Pierre [Université Catholique de Louvain - UCL > CHU Mont-Godinne > > >]
Delbrück, Heinrich [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Bennink, Sandra [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Kupper, Michaël [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Rezende de Castro, Roberta [Université Catholique de Louvain - UCL > CHU Mont-Godinne > > >]
Glupczynski, Youri [Université Catholique de Louvain - UCL > CHU Mont-Godinne > > >]
Hoffmann, Kurt [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > > >]
Jan-2013
Antimicrobial Agents and Chemotherapy
American Society for Microbiology (ASM)
57(1)
396-401
Yes (verified by ORBi)
International
0066-4804
1098-6596
Washington
DC
[en] A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.
Alexander von Humboldt Foundation (Germany) - AvH
http://hdl.handle.net/2268/143573
10.1128/AAC.01784-12
We acknowledge the American Society for Microbiology.

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