Article (Scientific journals)
GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from pseudomonas aeruginosa that contains Ile80 and Ser170 residues.
Bebrone, Carine; Bogaerts, Pierre; Delbrück, Heinrich et al.
2013In Antimicrobial Agents and Chemotherapy, 57(1), p. 396-401
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Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bebrone, Carine ;  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
Language :
English
Title :
GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from pseudomonas aeruginosa that contains Ile80 and Ser170 residues.
Publication date :
January 2013
Journal title :
Antimicrobial Agents and Chemotherapy
ISSN :
0066-4804
eISSN :
1098-6596
Publisher :
American Society for Microbiology (ASM), Washington, United States - District of Columbia
Volume :
57(1)
Pages :
396-401
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
AvH - Alexander von Humboldt-Stiftung [DE]
Available on ORBi :
since 22 February 2013

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