Molecular Characterization of a β-Lactamase Gene, bla GIM-1 , Encoding a New Subclass of Metallo-β-Lactamase

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Abstract
As part of the SENTRY Antimicrobial Surveillance Program in 2002, five multidrug-resistant Pseudomonas aeruginosa clinical isolates were detected with metallo-β-lactamase (MβL) activity. The isolates were recovered from different patients in a medical center located in Dusseldorf, Germany. The resistant determinant was isolated amplifying the region between the integrase and the aacA4 gene cassette. Sequencing revealed a novel MβL gene, designated blaGIM-1. Additional analysis showed that GIM-1, comprising 250 amino acids and with a pI value of 5.4, differs in its primary sequence from that described for IMP, VIM, and SPM-1 enzymes by 39 to 43%, 28 to 31%, and 28%, respectively. The enzyme possesses unique amino acids within the major consensus sequence (HXHXD) of the MβL family. Kinetics analysis revealed that GIM-1 has no clear preference for any substrate and did not hydrolyze azlocillin, aztreonam, and the serine-β-lactamase inhibitors. blaGIM-1 was found on a 22-kb nontransferable plasmid. The new MβL gene was embedded in the first position of a 6-kb class 1 integron, In77, with distinct features, including an aacA4 cassette downstream of the MβL gene that appeared to be truncated with blaGIM-1. The aacA4 was followed by an aadA1 gene cassette that was interrupted by a copy of the IS1394. This integron also carried an oxacillinase gene, blaOXA-2, before the 3′-CS region. GIM-1 appears to be a unique MβL, which is located in a distinct integron structure, and represents the fourth subclass of mobile MβL enzymes to be characterized.

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