GES-18, a New Carbapenem-Hydrolyzing GES-Type β-Lactamase from Pseudomonas aeruginosa That Contains Ile80 and Ser170 Residues

Abstract

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 ␤-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.

VIM-1, VIM-2, and GES-5 Carbapenemases Among Pseudomonas aeruginosa Isolates at a Tertiary Hospital in Istanbul, Turkey

“…28,[32][33][34] Recently, GES-18, which differs from GES-5 by one amino acid substitution, was identified from a P. aeruginosa isolate from Belgium. 30 To our knowledge, this is the second report of a clinical isolate of P. aeruginosa carrying the bla GES-5 gene in Turkey. In this study, the patient infected with the GES-positive P. aeruginosa died due to hospital-acquired pneumonia caused by this agent.…”

Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii : Mechanisms and epidemiology

“…Recently, a novel GES variant, GES-18, was identified from a P. aeruginosa isolate from Belgium. GES-18 differed from GES-5 by one amino acid substitution and also hydrolysed carbapenems [95].…”

Emergence and Plasmid Analysis of Klebsiella pneumoniae KP01 Carrying bla GES-5 from Guangzhou, China

“…Twenty-nine GES variants, which are commonly encoded by gene cassettes within integrons, have been deposited in the GenBank database (http://www.ncbi.nlm .nih.gov/nuccore/). Carbapenem hydrolytic activity has been demonstrated in some of these variants (GES-2, GES-4, GES-5, GES-6, GES-14, and GES-18) possessing a substitution at the Gly170 residue (1,(3)(4)(5)(6)(7). Nosocomial transmission of Enterobacteriaceae isolates carrying the carbapenem-hydrolyzing GES variants, predominantly GES-5, is a potential challenge for infection control.…”

“…he GES-type extended-spectrum ␤-lactamases (ESBLs) are reported increasingly for clinical Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii (1)(2)(3). Twenty-nine GES variants, which are commonly encoded by gene cassettes within integrons, have been deposited in the GenBank database (http://www.ncbi.nlm .nih.gov/nuccore/).…”