Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance

Abstract

A clinical isolate of Serratia marcescens (TN9106) produced a metallo 13-lactamase (IMP-1) which conferred resistance to imipenem and broad-spectrum 13-lactams. The consensus amino acid residues, His-95, His-97, Cys-176, and His-215, which form putative zinc ligands, were conserved in the deduced amino acid sequence of IMP-1. By determination of the amino acid sequence at the N terminus of purified mature IMP-1, 18 amino acid residues were found to be processed from the N terminus of the premature enzyme as a signal peptide. These results clearly show that IMP-1 is an enterobacterial metallo 13-lactamase, of which the primary structure has been completely determined, that confers resistance to carbapenems and other broad-spectrum 13-lactams.Many extended-spectrum 13-lactamases conferring high levels of resistance to broad-spectrum P-lactam antibiotics have been found worldwide with the increasing use of newly developed broad-spectrum P-lactam antibiotics (10, 11).They are mostly R plasmid-mediated TEM-or SHV-related class A enzymes (4,12,18,22,29,32). However, plasmidmediated AmpC-type ,-lactamases that belong to class C have recently been reported (9, 21). These plasmid-mediated extended-spectrum ,B-lactamases have a serine residue at the active center of the enzyme, and they effectively hydrolyze broad-spectrum ,-lactams, except carbapenems. Although it was reported by genetic analyses that bacteria belonging to the family Enterobacteriaceae, except Klebsiella spp. (1, 2) and Pseudomonas spp., have chromosomally encoded inducible AmpC 3-lactamases (8,14,16,20,26,34) times show resistance to imipenem and broad-spectrum P-lactams (7,17,37). The imipenem resistances of these bacteria are mainly due to the production of metallo 3-lactamases that belong to class B. The class B enzymes require zinc ions for enzyme activity and demonstrate a primary structure quite different from those of the class A and class C enzymes belonging to the group of serine P-lactamases.Recently, several strains of Serratia marcescens were reported to show resistance to carbapenems as well (35). In this study, we clearly show that a clinically isolated strain of S. marcescens (TN9106) showing resistance to imipenem has a chromosomally encoded metallo 3-lactamase gene.

Relevance of resistance levels to carbapenems and integron-borne bla IMP-1, bla IMP-7, bla IMP-10 and bla VIM-2 in clinical isolates of Pseudomonas aeruginosa

“…The bla IMP-1 gene was the first MBL determinant reported, initially in a clinical isolate of Serratia marcescens (Ito et al, 1995;Osano et al, 1994). The bla IMP-7 gene is a bla IMP allele and IMP-7 shares 91 % amino acid identity with IMP-1 (Gibb et al, 2002).…”

Emerging Carbapenem-Resistant <i>Enterobacter cloacae</i> Producing OXA-48-, VIM- and IMP-Type-<i>β</i>-Lactamases in Eastern Cape Hospitals in South Africa

“…The dominant genes contributing to drug resistance in E. cloacae are the plasmid-mediated serine extended spectrum β-lactamase (ESBL) bla CTX-M ; the serine carbapenemase bla KPC and the metallo-β-lacatamases (MBLs) bla NDM , bla IMP and bla VIM [4] [5]. The acquired MBL, bla IMP-1 emerged and spread in Gram-negative bacilli in Japan in the early 1990s [6] and together with its variants have since been detected in other countries worldwide [7]- [12]. bla VIM-1 was first reported in Italy, also in the 1990s [13].…”

Metalo-beta-lactamases

“…Atualmente são conhecidas cinco subclasses de MßL adquiridas: IMP (imipenemase) (46) , VIM (Verona imipenemase) (33) , SPM (São Paulo metalo-ß-lactamase) (72) , GIM (German imipenemase) (10) e, mais recentemente, SIM-1, codificada pelo gene bla SIM-1 detectado em sete A. baumannii isolados de um hospital terciário em Seul, Coréia (35) . O primeiro relato de MßL adquirida ocorreu em 1994 (46) , quando foi descrita uma nova subclasse denominada IMP-1. Essa enzima foi detectada em uma cepa clínica de Serratia marcescens isolada no Japão, a qual apresentava fenótipo de resistência a imipenem e cefalosporinas de espectro ampliado.…”

“…No entanto, já houve relatos da produção dessas enzimas por microrganismos pertencentes à família Enterobacteriaceae (32,46,80) . O primeiro relato de uma MßL no continente americano ocorreu em 2002 por Gibb et al (25) .…”