Nomenclature of GES-Type Extended-Spectrum β-Lactamases

Abstract

In two recently published articles, Wachino et al. designated a novel ceftazidime-hydrolyzing class A extended-spectrum β-lactamase (ESBL) (GES-a) as GES-3 (4), and a new cephamycin-hydrolyzing and inhibitor-resistant class A ESBL (GES-b) as GES-4 (5). In actuality, their articles are fraught with misleading nomenclature of GES-type ESBLs and controvertible conclusions on the relationship between β-lactamase inhibitor resistance and an amino acid substitution in the center of the Ω-loop region. Before Wachino and colleagues submitted their sequences for GES-a and GES-b genes to the GenBank nucleotide databank (release dates, 25 May 2004 and 28 July 2004, respectively), sequences for GES-3 and GES-4 genes had already been released by Vourli et al. (3), the release date of which was 12 May 2004. As shown in Table ​Table1,1, GES-a and GES-b genes are completely different from GES-3 and GES-4 genes. GES-3 and GES-4 were capable of hydrolyzing imipenem (3), while GES-a could not hydrolyze imipenem and GES-b had a substrate profile extended to cephamycins as well as imipenem (4, 5). Presently, the different GES-type ESBLs have been designated by identical names. On the basis of priority of nomenclature, GES-a and GES-b genes should be renamed as GES-5 and GES-6 genes, respectively. TABLE 1. Amino acid substitutions of GES-type ESBLs In their efforts to persuade readers that GES-b has a strong inhibitor-resistant nature like IRT enzymes and that it maintains the capacity to hydrolyze cephamycins and imipenem as a result of a single substitution at position 170, the center of the Ω-loop region, Wachino et al. (5) stated: “In comparison with GES-1, GES-2 [containing a single substitution at position 170] showed an extended substrate specificity for imipenem and a lower affinity for β-lactamase inhibitors (1), as was seen with GES-4 [GES-b].” However, Poirel et al. (1) stated: “Inhibition studies as measured by IC50s with benzylpenicillin as a substrate showed that GES-2 activity was inhibited by clavulanic acid and tazobactam more than GES-1 is.” The IC50s (inhibitory concentrations) of clavulanic acid and tazobactam for GES-b (15.2 and 1.43 μM, respectively) were higher than those of GES-1 (5 and 2.5 μM, respectively), GES-2 (1 and 0.5 μM, respectively), and GES-a (1.5 and 0.19 μM, respectively). Two GES-type ESBLs (GES-2 and GES-b) containing a single substitution at position 170 showed a different inhibition profile. Although GES-b has a strong inhibitor-resistant nature like IRT enzymes, the conclusion that the G170S substitution found in the GES-b affected inhibitor resistance could not be supported by the data as presented. The renaming of GES-a and GES-b can help some authors to correctly designate new GES-type ESBLs, such as the novel enzymes identified from our nationwide survey supported by the Korea Research Foundation (KRF-2004-042-{type:entrez-nucleotide,attrs:{text:E00117,term_id:2168418,term_text:E00117}}E00117).