CASTANHEIRA M, MENDES RE, SCHMITZ F, TOLEMAN M, JONES RN, WALSH TR; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. C1-669.
University of Bristol, Bristol, United Kingdom.
BACKGROUND: There are three major types of mobile metallo-beta-lactamase (MBL) genes; blaIMP, blaVIM an blaSPM. As part of the SENTRY Program, numerous P. aeruginosa (PSA) have been screened for high resistance (R) to carbapenems (imipenem [IMP] and meropenem [MER]) and ceftazidime (CTZ). Five PSA isolates from Dusseldorf were detected, the index strain from a 37 yo male ICU patient with nosocomial pneumonia. METHODS: MBL production was confirmed by the Etest MBL strip and was further studied by biochemical assay techniques. Isolates that were PCR-negative for blaIMP, blaVIM and blaSPM, were screened by amplifying the region between the integrase and aacA4 genes. Amplicons (>500bp) were sequenced. Hydrolysis rates were measured for 10 beta-lactams and inhibition analysis used aztreonam (ATM), clavulanic acid (CA) and EDTA. RESULTS: Sequence analysis revealed a novel MBL gene, designated blaGIM-1. The gene lies between a Class 1 integron and accA4 within a 6.0kb integron. blaGIM-1 is carried on a large plasmid and can transform E. coli to CTZ resistance. GIM-1 comprises 250 amino acids (MW, 25.5Kda) and a pI value of 5.4. GIM-1 differs from the IMP, VIM and SPM-1 enzymes by 39 - 43%, 28 - 31% and 28%, respectively. GIM-1 also possesses a unique main active site, HSHEDR. GIM-1 actively hydrolyses IMP, MER, penicillins and cephalosporins, where IMP and cefotaxime are the preferred substrates. ATM and CA showed very unusual kinetic properties. These features indicate a new type of MBL. CONCLUSIONS: GIM-1 is a unique MBL and represents the fourth type of mobile MBL to be characterised. blaGIM is associated with a Class 1 integron and comprises part of a large gene cassette including accA4. These data indicate that PSA therapies in Europe may be further compromised by the dissemination of this and previously documented MBL genes.
Publication Types:
Keywords:
- Anti-Bacterial Agents
- Anti-Infective Agents
- Base Sequence
- Carbapenems
- Europe
- Humans
- Imipenem
- Integrons
- Male
- Plasmids
- Thienamycins
- beta-Lactamases
- beta-Lactams
- classification
- genetics
- meropenem
Other ID:
UI: 102264746
From Meeting Abstracts