References of "Galleni, Moreno"
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See detailStructural basis for the broad-spectrum inhibition of metallo-beta-lactamases by thiols
Lienard, Benoit M R; Garau, Gianpiero; Horsfall, Louise et al

in Organic & Biomolecular Chemistry (2008), 6(13), 2282-2294

The development of broad-spectrum metallo-beta-lactamase (MBL) inhibitors is challenging due to structural diversity and differences in metal utilisation by these enzymes. Analysis of structural data ... [more ▼]

The development of broad-spectrum metallo-beta-lactamase (MBL) inhibitors is challenging due to structural diversity and differences in metal utilisation by these enzymes. Analysis of structural data, followed by non-denturing mass spectrometric analyses, identified thiols proposed to inhibit representative MBLs from all three sub-classes: B1, B2 and B3. Solution analyses led to the identification of broad spectrum inhibitors, including potent inhibitors of the CphA MBL (Aeromonas hydrophila). Structural studies revealed that, as observed for other B1 and B3 MBLs, inhibition of the L1 MBL thiols involves metal chelation. Evidence is reported that this is not the case for inhibition of the CphA enzyme by some thiols; the crystal structure of the CphA-Zn-inhibitor complex reveals a binding mode in which the thiol does not interact with the zinc. The structural data enabled the design and the production of further more potent inhibitors. Overall the results suggest that the development of reasonably broad-spectrum MBL inhibitors should be possible. [less ▲]

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See detailRelationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 activation mechanism
Chevigné, Andy ULg; Barumandzadeh, Roya ULg; Groslambert, Sylvie et al

in Journal of Molecular Biology (2007), 374(1), 170-185

The major allergen Der p1 of the house dust mite Dermatophagoides pteronyssinus is a papain-like cysteine protease (CA1) produced as an inactive precursor and associated with allergic diseases. The ... [more ▼]

The major allergen Der p1 of the house dust mite Dermatophagoides pteronyssinus is a papain-like cysteine protease (CA1) produced as an inactive precursor and associated with allergic diseases. The propeptide of Der p I exhibits a specific fold that makes it unique in the CA1 propeptide family. In this study, we investigated the activation steps involved in the maturation of the recombinant protease Der p 1 expressed in Pichia pastoris and the interaction of the full-length and truncated soluble propepticles with their parent enzyme in terms of activity inhibition and BIAcore interaction analysis. According to our results, the activation of protease Der p 1 is a multistep mechanism that is characterized by at least two intermediates. The propeptide strongly inhibits unglycosylated and glycosylated recombinant Der p 1 (K-D = 7 nM) at neutral pH. This inhibition is pH dependent. It decreases from pH 7 to pH 4 and can be related to conformational changes of the propepticle characterized by an increase of its flexibility and formation of a molten globule state. Our results indicate that activation of the zymogen at pH 4 is a compromise between activity preservation and propeptide unfolding. (c) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailPurification of the recombinant beta2 toxin (CPB2) from an enterotoxaemic bovine Clostridium perfringens strain and production of a specific immune serum
Lebrun, Maud; Filée, Patrice ULg; Galleni, Moreno ULg et al

in Protein Expression & Purification (2007), 55(1), 119-131

Overgrowth of Clostridium perfringens clones with production of one or more of its toxin(s) results in diverse digestive and systemic pathologies in human and animals, such as cattle enterotoxaemia. The ... [more ▼]

Overgrowth of Clostridium perfringens clones with production of one or more of its toxin(s) results in diverse digestive and systemic pathologies in human and animals, such as cattle enterotoxaemia. The so-called beta2 toxin (CPB2) is the most recently described major toxin produced by C perfringens. In this study, the cpb2 ORF (cpb2FM) from a cattle C perfringens-associated enterotoxaemia was cloned and sequenced. The cpb2FM and its deduced nucleotide sequence clearly corresponded to the epb2 allele considered as "consensus" and not to "atypical" allele, despite its "non-porcine" origin. Expression assays of the recombinant toxin CPB2FM were performed in Escherichia coli and Bacillus subtilis with the expression vector pBLTS72, and by genomic integration by double recombination in B. subtilis. Highest level of production was obtained with the expression vector in B. subtilis 168 strain. The recombinant CPB2FM protein was purified and a specific rabbit polyclonal antiserum was produced. Polyclonal antibodies could detect CPB2 production in supernatants of C. perfringens from enterotoxaemic cattle. (C) 2007 Elsevier Inc. All rights reserved. [less ▲]

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See detailBiosensors based on electrochemically prepared polyanilines and bifunctional hybrid proteins
Faure, Emilie ULg; Halusiak, Emilie; Ruth, Nadia ULg et al

Poster (2007, August 31)

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See detailCompetitive inhibitors of the CphA metallo-beta-lactamase from Aeromonas hydrophila
Horsfall, L. E.; Garau, G.; Lienard, B. M. et al

in Antimicrobial Agents and Chemotherapy (2007), 51(6), 2136-2142

Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with ... [more ▼]

Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with one zinc) either contain a thiol (and show less inhibition towards this subgroup than towards the dizinc members of B1 and B3) or are inactivators behaving as substrates for the dizinc family members. The present work reveals that certain pyridine carboxylates are competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner within the active site. Salts of these compounds are already available and undergoing biomedical testing for various nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases. [less ▲]

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See detailMetallo-beta-lactamases as emerging resistance determinants in Gram-negative pathogens: open issues
Cornaglia, G.; Akova, M.; Amicosante, G. et al

in International Journal of Antimicrobial Agents (2007), 29(4), 380-388

The rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of particular concern worldwide and primarily in Europe, one of first continents where the ... [more ▼]

The rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of particular concern worldwide and primarily in Europe, one of first continents where the emergence of acquired MBLs has been reported and possibly the geographical area where the increasing diversity of these enzymes and the number of bacterial species affected are most impressive. This spread has not been paralleled by accuracy/standardisation of detection methods, completeness of epidemiological knowledge or a clear understanding of what MBL production entails in terms of clinical impact, hospital infection control and antimicrobial chemotherapy. A number of European experts in the field met to review the current knowledge on this phenomenon, to point out open issues and to reinforce and relate to one another the existing activities set forth by research institutes, scientific societies and European Union-driven networks. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. [less ▲]

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See detailThe Bacillus licheniformis BlaP beta-lactamase as a model protein scaffold to study the insertion of protein fragments.
Vandevenne, Marylène ULg; Filée, Patrice ULg; Scarafone, Natacha ULg et al

in Protein Science : A Publication of the Protein Society (2007), 16(10), 2260-71

Using genetic engineering technologies, the chitin-binding domain (ChBD) of the human macrophage chitotriosidase has been inserted into the host protein BlaP, a class A beta-lactamase produced by Bacillus ... [more ▼]

Using genetic engineering technologies, the chitin-binding domain (ChBD) of the human macrophage chitotriosidase has been inserted into the host protein BlaP, a class A beta-lactamase produced by Bacillus licheniformis. The product of this construction behaved as a soluble chimeric protein that conserves both the capacity to bind chitin and to hydrolyze beta-lactam moiety. Here we describe the biochemical and biophysical properties of this protein (BlaPChBD). This work contributes to a better understanding of the reciprocal structural and functional effects of the insertion on the host protein scaffold and the heterologous structured protein fragments. The use of BlaP as a protein carrier represents an efficient approach to the functional study of heterologous protein fragments. [less ▲]

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See detailThe expression of Clostridium perfringens consensus beta2 toxin is associated with bovine enterotoxaemia syndrome
Lebrun, Maud; Filée, Patrice ULg; Mousset, Bénédicte ULg et al

in Veterinary Microbiology (2007), 120(1-2), 151-157

Clostridium perfringens has been implicated in a broad array of enteric infections including the fatal haemorrhagic enteritis/enterotoxaemia syndrome in cattle. The beta2 toxin (CPB2), encoded by cpb2, is ... [more ▼]

Clostridium perfringens has been implicated in a broad array of enteric infections including the fatal haemorrhagic enteritis/enterotoxaemia syndrome in cattle. The beta2 toxin (CPB2), encoded by cpb2, is suspected to be implicated in this syndrome. However, among C. perfringens isolates from cattle suspected of clostridial disease, an atypical allele was recently found to predominate at the cpb2 locus and atypical corresponding CPB2 proteins were shown to be poorly expressed, thus arguing against a biologically significant role of the beta2 toxin in clostridial diseases in cattle. This study compared genotype and phenotype of the beta2 toxin between C. perfringens isolates from a group of healthy calves (n = 14, 87 isolates) and from a group of enterotoxaemic calves (n = 8,41 isolates). PCR results revealed the exclusive presence of the typical "consensus" cpb2 in the enterotoxaernic group. Western blot analysis demonstrated that the typical variant of CPB2 was often expressed in isolates from enterotoxaemic calves (43.9%) and infrequently in isolates from healthy cattle (6.9%). These data suggest that the typical variant of the CPB2 toxin may play a role in the pathogenesis of cattle enterotoxaemia. (c) 2006 Elsevier B.V. All rights reserved. [less ▲]

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See detailA novel extended-spectrum TEM-type beta-lactamase, TEM-138, from Salmonella enterica serovar Infantis.
chouchani, chedli; Berlemont, Renaud ULg; masmoudi, A. et al

in Antimicrobial Agents and Chemotherapy (2006), 50(9), 3183-5

A novel natural TEM beta-lactamase with extended-spectrum activity, TEM-138, was identified in a ceftazidime-resistant clinical isolate of Salmonella enterica serovar Infantis. Compared to TEM-1, TEM-138 ... [more ▼]

A novel natural TEM beta-lactamase with extended-spectrum activity, TEM-138, was identified in a ceftazidime-resistant clinical isolate of Salmonella enterica serovar Infantis. Compared to TEM-1, TEM-138 contains the following mutations: E104K, N175I, and G238S. The bla(TEM-138) gene was located on a 50-kb transferable plasmid. Expression studies with Escherichia coli revealed efficient ceftazidimase and cefotaximase activities for TEM-138. [less ▲]

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See detailPolyolefin matrixes with permanent antibacterial activity : preparation, antibacterial activity, and action mode of the active species
Lenoir, Sandrine ULg; Pagnoulle, Christophe; Galleni, Moreno ULg et al

in Biomacromolecules (2006), 7(8), 2291-2296

Poly[2-(tert-butylamino)ethyl methacrylate] (PTBAEMA) belongs to a novel class of water-insoluble biocides. Dispersion of a poly(ethylene-co-butylene)-b-poly[2-(tert-butylamino)ethyl methacrylate] diblock ... [more ▼]

Poly[2-(tert-butylamino)ethyl methacrylate] (PTBAEMA) belongs to a novel class of water-insoluble biocides. Dispersion of a poly(ethylene-co-butylene)-b-poly[2-(tert-butylamino)ethyl methacrylate] diblock copolymer (PEB-b-PTBAEMA) within low-density polyethylene (LDPE) imparts antimicrobial properties to the polyolefin as assessed by the viable cell counting method against Escherichia coli (E. coli). This diblock copolymer has been synthesized by atom transfer radical polymerization (ATRP) with a poly(ethylene-co-butylene) (PEB) oligomer end-capped by an activated bromide as a macroinitiator for the polymerization of 2-(tert-butylamino)ethyl methacrylate (TBAEMA). Morphological changes of E. coli bacteria in contact with modified LDPE have been observed by transmission and scanning electron microscopy and indicate that the diblock copolymer is bactericide rather than bacteriostatic. Finally, the action mode of the PEB-b-PTBAEMA copolymer more likely relies on the displacement of the Ca2+ and/or Mg2+ ions of the outer membrane of the bacteria, which is disorganized and finally disrupted. [less ▲]

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See detailNew antibacterial cationic surfactants prepared by Atom Transfer Radical Polymerization
Lenoir, Sandrine ULg; Pagnoulle, Christophe; Detrembleur, Christophe ULg et al

in Journal of Polymer Science. Part A, Polymer Chemistry (2006), 44(3), 1214-1224

Efficient antibacterial surfactants have been prepared by the quaternization of the amino groups of poly(ethylene-co-butylene)-b-poly[2-(dimethylamino)ethylmethacrylate] (PEB-b-PDMAEMA) diblock copolymers ... [more ▼]

Efficient antibacterial surfactants have been prepared by the quaternization of the amino groups of poly(ethylene-co-butylene)-b-poly[2-(dimethylamino)ethylmethacrylate] (PEB-b-PDMAEMA) diblock copolymers by octyl bromide. The diblock copolymers have been synthesized by ATRP of 2-(dimethylamino)ethylmethacrylate (DMAEMA) initiated by an activated bromide-end-capped poly(ethylene-co-butylene). In the presence of CuBr, 1,4,7,10,10-hexamethyl-triethylenetetramine (HMTETA), and toluene at 50 °C, the initiation is slow in comparison with propagation. This situation has been improved by the substitution of CuCl for CuBr, all the other conditions being the same. Finally, the addition of an excess of CuCl2 (deactivator) to the CuCl/HMTETA catalyst is very beneficial in making the agreement between the theoretical and experimental number-average molecular weights excellent. The antibacterial activity of PEB-b-PDMAEMA quaternized by octyl bromide has been assessed against bacteria and is comparable to the activity of a commonly used disinfectant, that is, benzalkonium chloride. [less ▲]

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See detailMonitoring the zinc affinity of the metallo-beta-lactamase CphA by automated nanoESI-MS
De Vriendt, K.; Van Driessche, G.; Devreese, B. et al

in Journal of the American Society for Mass Spectrometry (2006), 17(2), 180-188

Metallo-beta-lactamases are zinc containing enzymes that are able to hydrolyze and inactivate beta-lactam antibiotics. The subclass B2 enzyme CphA of Aeromonas hydrophila is a unique metallo-p-lactamase ... [more ▼]

Metallo-beta-lactamases are zinc containing enzymes that are able to hydrolyze and inactivate beta-lactam antibiotics. The subclass B2 enzyme CphA of Aeromonas hydrophila is a unique metallo-p-lactamase because it degrades only carbapenems efficiently and is only active when it has one zinc ion bound. A zinc titration experiment was used to study the zinc affinity of the wild-type and of several mutant CphA enzymes. It shows that a second Zn2+ is also bound at high ion concentrations. All samples were analyzed using mass spectrometry in combination with an automated nanoESI source. The metal-free enzyme has a bimodal charge distribution indicative of two conformational states. A completely folded enzyme is detected when the apo-enzyme has bound the first zinc. Intensity ratios of the different enzyme forms were used to deduce the zinc affinities. CphA enzymes mutated in metal ligands show decreased zinc affinity compared to wild-type, especially D120 mutants. [less ▲]

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See detailCrystal structure of the Mycobacterium fortuitum class A beta-lactamase: structural basis for broad substrate specificity.
Sauvage, Eric ULg; Fonze, Eveline; Quinting, Birgit et al

in Antimicrobial Agents and Chemotherapy (2006), 50(7), 2516-21

beta-Lactamases are the main cause of bacterial resistance to penicillins and cephalosporins. Class A beta-lactamases, the largest group of beta-lactamases, have been found in many bacterial strains ... [more ▼]

beta-Lactamases are the main cause of bacterial resistance to penicillins and cephalosporins. Class A beta-lactamases, the largest group of beta-lactamases, have been found in many bacterial strains, including mycobacteria, for which no beta-lactamase structure has been previously reported. The crystal structure of the class A beta-lactamase from Mycobacterium fortuitum (MFO) has been solved at 2.13-A resolution. The enzyme is a chromosomally encoded broad-spectrum beta-lactamase with low specific activity on cefotaxime. Specific features of the active site of the class A beta-lactamase from M. fortuitum are consistent with its specificity profile. Arg278 and Ser237 favor cephalosporinase activity and could explain its broad substrate activity. The MFO active site presents similarities with the CTX-M type extended-spectrum beta-lactamases but lacks a specific feature of these enzymes, the VNYN motif (residues 103 to 106), which confers on CTX-M-type extended-spectrum beta-lactamases a more efficient cefotaximase activity. [less ▲]

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See detailAntimicrobial activity of polyestyrene particles coated by photo-crooslinked block copolymers containing a biocidal polymethacrylate block
Lenoir, Sandrine ULg; Pagnoulle, Christophe; Detrembleur, Christophe ULg et al

in e-Polymers (2005), 74

A commercially available poly(ethylene-co-butylene) copolymer, end-capped by a short polyisoprene block and a hydroxyl group (PI-b-PEB-OH), has been derivatized into a macroinitiator for atom transfer ... [more ▼]

A commercially available poly(ethylene-co-butylene) copolymer, end-capped by a short polyisoprene block and a hydroxyl group (PI-b-PEB-OH), has been derivatized into a macroinitiator for atom transfer radical polymerization (ATRP) by esterification of the hydroxyl end-group by an activated bromide-containing acyl bromide. Two types of triblock copolymers, Pl-b-PEB-b-poly(dimethylaminoethyl methacrylate) (PDMAEMA) and Pl-b-PEB-b-poly[2-(tert-butylamino)ethyl methacrylate] (PTBAEMA), have been synthesized and used to coat polystyrene particles. These coatings have been permanently immobilized by UV cross-linking of the isoprene units. They exhibit a biocidal activity against Gram-negative bacteria either intrinsically in case of the PTBAEMA block or upon quaternization of the PDMAEMA block by octyl bromide. The antimicrobial activity is directly related to the concentration of coated PS particles in the medium. [less ▲]

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See detailFrom dormant to germinating spores of Streptomyces coelicolor A3(2): new perspectives from the crp null mutant.
Piette, André ULg; Derouaux, Adeline ULg; Gerkens, Pascal et al

in Journal of Proteome Research (2005), 4(5), 1699-708

The complete understanding of the morphological differentiation of streptomycetes is an ambitious challenge as diverse sensors and pathways sensitive to various environmental stimuli control the process ... [more ▼]

The complete understanding of the morphological differentiation of streptomycetes is an ambitious challenge as diverse sensors and pathways sensitive to various environmental stimuli control the process. Germination occupies a particular position in the life cycle as the good achievement of the process depends on events occurring both during the preceding sporulation and during germination per se. The cyclic AMP receptor protein (crp) null mutant of Streptomyces coelicolor, affected in both sporulation and germination, was therefore presented as a privileged candidate to highlight new proteins involved in the shift from dormant to germinating spores. Our multidisciplinary approach-combining in vivo data, the analysis of spores morphological properties, and a proteome study-has shown that Crp is a central regulatory protein of the life cycle in S. coelicolor; and has identified spores proteins with statistically significant increased or decreased expression that should be listed as priority targets for further investigations on proteins that trigger both ends of the life cycle. [less ▲]

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See detailDramatic broadening of the substrate profile of the Aeromonas hydrophila CphA metallo-beta-lactamase by site-directed mutagenesis
Bebrone, Carine ULg; Anne, C.; De Vriendt, K. et al

in Journal of Biological Chemistry (2005), 280(31), 28195-28202

Among class B beta-lactamases, the subclass B2 CphA enzyme is characterized by a unique specificity profile. CphA efficiently hydrolyzes only carbapenems. In this work, we generated site-directed mutants ... [more ▼]

Among class B beta-lactamases, the subclass B2 CphA enzyme is characterized by a unique specificity profile. CphA efficiently hydrolyzes only carbapenems. In this work, we generated site-directed mutants that possess a strongly broadened activity spectrum when compared with the WT CphA. Strikingly, the N116H/N220G double mutant exhibits a substrate profile close to that observed for the broad spectrum subclass B1 enzymes. The double mutant is significantly activated by the binding of a second zinc ion under conditions where the WT enzyme is non-competitively inhibited by the same ion. [less ▲]

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See detailATRP of aminated methacrylates: a route to effective antimicrobial surfactants, coatings and additives
Lenoir, Sandrine; Pagnoulle, Christophe; Detrembleur, Christophe ULg et al

Conference (2005, June 01)

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