Interaction of Cefotetan and the Metallo-β-Lactamases Produced in &lt;i&gt;Aeromonas&lt;/i&gt; spp. and in vitro Activity

Quiroga, M.P.; Franceschini, Nicola; Rossolini, Gian María; Gutkind, Gabriel; Bonfiglio, Giovanni; Franchino, L; Amicosante, Gianfranco

doi:10.1159/000007275

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…and the Serratia fonticola enzyme SFH-1. MBL L1 is the sole occupant of the class B3 enzymes, as it is singularly unique among all ␤-lactamases in being functionally represented as a tetramer (140).…”

Section: Classification Of Mblsmentioning

confidence: 99%

Metallo-β-Lactamases: the Quiet before the Storm?

et al. 2005

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SUMMARY The ascendancy of metallo-β-lactamases within the clinical sector, while not ubiquitous, has nonetheless been dramatic; some reports indicate that nearly 30% of imipenem-resistant Pseudomonas aeruginosa strains possess a metallo-β-lactamase. Acquisition of a metallo-β-lactamase gene will invariably mediate broad-spectrum β-lactam resistance in P. aeruginosa, but the level of in vitro resistance in Acinetobacter spp. and Enterobacteriaceae is less dependable. Their clinical significance is further embellished by their ability to hydrolyze all β-lactams and by the fact that there is currently no clinical inhibitor, nor is there likely to be for the foreseeable future. The genes encoding metallo-β-lactamases are often procured by class 1 (sometimes class 3) integrons, which, in turn, are embedded in transposons, resulting in a highly transmissible genetic apparatus. Moreover, other gene cassettes within the integrons often confer resistance to aminoglycosides, precluding their use as an alternative treatment. Thus far, the metallo-β-lactamases encoded on transferable genes include IMP, VIM, SPM, and GIM and have been reported from 28 countries. Their rapid dissemination is worrisome and necessitates the implementation of not just surveillance studies but also metallo-β-lactamase inhibitor studies securing the longevity of important anti-infectives.

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Section: Classification Of Mblsmentioning

confidence: 99%

Metallo-β-Lactamases: the Quiet before the Storm?

et al. 2005

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“…Some of the reported inhibitors of these enzymes include trifluoromethyl alcohols and ketones (41), amino acid-derived hydroxamates (42), thiols (3,4,12,13), thioester derivatives (13,14,31,32), cysteinyl peptides (5), biphenyl tetrazoles (38,39), mercaptocarboxylates (24,30), 1␤-methylcarbapenem derivatives (25,26), a synthetic cephamycin (34), and 2,3-disubstituted succinic acid derivatives (40).…”

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confidence: 99%

N-Arylsulfonyl Hydrazones as Inhibitors of IMP-1 Metallo-β-Lactamase

Siemann

Evanoff

Marrone

et al. 2002

Antimicrob Agents Chemother

107

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Members of a family of N-arylsulfonyl hydrazones have been identified as novel inhibitors of IMP-1, a metallo-␤-lactamase of increasing prevalence. Structure-activity relationship studies have indicated a requirement for bulky aromatic substituents on each side of the sulfonyl hydrazone backbone for these compounds to serve as efficient inhibitors of IMP-1. Molecular modeling has provided insight into the structural basis for the anti-metallo-␤-lactamase activity exhibited by this class of compounds.

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“…Only carbapenems are efficiently hydrolyzed by these enzymes (13), while all other ␤-lactams are poor substrates. In addition, cephamycins and oxacephems behave as poor inactivators of CphA (14,27).The enzymes belonging to subclass B3 can be either monomeric (GOB-1) or multimeric (L1). Detailed kinetic studies performed on the L1 and GOB-1 metallo-␤-lactamases showed that the enzymes exhibit broad-spectrum activity profiles (2, 10).…”

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confidence: 99%

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confidence: 99%

Biochemical Characterization of the FEZ-1 Metallo-β-Lactamase of Legionella gormanii ATCC 33297 ^T Produced in Escherichia coli

Mercuri

Bouillenne

Boschi

et al. 2001

Antimicrob Agents Chemother

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The bla FEZ-1 gene coding for the metallo-␤-lactamase of Legionella (Fluoribacter) gormanii ATCC 33297T was overexpressed via a T7 expression system in Escherichia coli BL21(DE3)(pLysS). The product was purified to homogeneity in two steps with a yield of 53%. The FEZ-1 metallo-␤-lactamase exhibited a broad-spectrum activity profile, with a preference for cephalosporins such as cephalothin, cefuroxime, and cefotaxime. Monobactams were not hydrolyzed. The ␤-lactamase was inhibited by metal chelators. FEZ-1 is a monomeric enzyme with a molecular mass of 29,440 Da which possesses two zinc-binding sites. Its zinc content did not vary in the pH range of 5 to 9, but the presence of zinc ions modified the catalytic efficiency of the enzyme. A model of the FEZ-1 three-dimensional structure was built.Metallo-␤-lactamases (class B of the molecular classification of Ambler [1] or group 3 according to the functional classification of Bush et al. [6]) constitute a very heterogeneous family. Although their primary structures exhibit low degrees of sequence isology (38) (generally less than 43%), their threedimensional structures show high degrees of similarity (7,8,9,12,35). All class B ␤-lactamases share five main characteristics (38): (i) they hydrolyze carbapenem compounds, (ii) they do not interact with monobactams, (iii) they are inhibited by chelating agents such as dipicolinic acid and 1,10-o-phenanthroline, (iv) they contain zinc ions as the naturally occurring cation, and (v) they exhibit two metal-binding sites.On the basis of structural analyses, these enzymes cluster into three different groups: subclass B1 contains most known zinc ␤-lactamases (for example, BcII (33,36) and the Chryseobacterium meningosepticum GOB-1 (2) and the Legionella (Fluoribacter) gormanii FEZ-1 (4) metallo-␤-lactamases.In the known crystal structures of metallo-␤-lactamases, Zn-1 is tetrahedrally coordinated to three histidines and a water molecule. When present, Zn-2 interacts with three residues (a cysteine, an aspartic acid, and a histidine in the case of BcII, IMP-1, and CcrA or an aspartic acid and two histidines for L1) and two water molecules in a trigonal pyramid. In the di-zinc form, one water molecule is bridged between the metal ions.The enzymes of subclass B1 are monomeric proteins. They possess a broad-spectrum activity profile (10,13,14,20,26,40) and are inhibited by thiol compounds such as SB25566 (9,16,34). Interestingly, the mono-and di-zinc form of the BcII and CcrA enzymes are nearly equally active. Kinetic and spectroscopic studies indicated that for both forms a transient noncovalent intermediate is formed during the hydrolysis of the substrate.To date, no structure of a subclass B2 enzyme is available. For these ␤-lactamases, the optimal activity is observed with the mono-zinc form. The second zinc ion behaves as a noncompetitive inhibitor (17). Only carbapenems are efficiently hydrolyzed by these enzymes (13), while all other ␤-lactams are poor substrates. In addition, cephamycins and oxacephems behave as poor inact...

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Interaction of Cefotetan and the Metallo-β-Lactamases Produced in <i>Aeromonas</i> spp. and in vitro Activity

Cited by 12 publications

References 29 publications

Metallo-β-Lactamases: the Quiet before the Storm?

Metallo-β-Lactamases: the Quiet before the Storm?

N-Arylsulfonyl Hydrazones as Inhibitors of IMP-1 Metallo-β-Lactamase

Biochemical Characterization of the FEZ-1 Metallo-β-Lactamase of Legionella gormanii ATCC 33297 ^T Produced in Escherichia coli

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Interaction of Cefotetan and the Metallo-β-Lactamases Produced in <i>Aeromonas</i> spp. and in vitro Activity

Cited by 12 publications

References 29 publications

Metallo-β-Lactamases: the Quiet before the Storm?

Metallo-β-Lactamases: the Quiet before the Storm?

N-Arylsulfonyl Hydrazones as Inhibitors of IMP-1 Metallo-β-Lactamase

Biochemical Characterization of the FEZ-1 Metallo-β-Lactamase of Legionella gormanii ATCC 33297 T Produced in Escherichia coli

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Biochemical Characterization of the FEZ-1 Metallo-β-Lactamase of Legionella gormanii ATCC 33297 ^T Produced in Escherichia coli