References of "Mercuri, Paola"
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See detailInteraction of Avibactam with Class B Metallo-β-Lactamases.
Abboud, MI; Damblon, Christian ULg; Brem, J et al

in Antimicrobial Agents and Chemotherapy (2016), 60

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See detailKinetic Studies on CphA Mutants Reveal the Role of the P158-P172 Loop in Activity versus Carbapenems.
Bottoni, Carlo; Perilli, Mariagrazia; Marcoccia, Francesca et al

in Antimicrobial Agents and Chemotherapy (2016), 60(5), 3123-6

Site-directed mutagenesis of CphA indicated that prolines in the P158-P172 loop are essential for the stability and the catalytic activity of subclass B2 metallo-beta-lactamases against carbapenems. The ... [more ▼]

Site-directed mutagenesis of CphA indicated that prolines in the P158-P172 loop are essential for the stability and the catalytic activity of subclass B2 metallo-beta-lactamases against carbapenems. The sequential substitution of proline led to a decrease of the catalytic efficiency of the variant compared to the wild-type (WT) enzyme but also to a higher affinity for the binding of the second zinc ion. [less ▲]

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See detailKinetic Study of Laboratory Mutants of NDM-1 Metallo-beta-Lactamase and the Importance of an Isoleucine at Position 35.
Marcoccia, Francesca; Bottoni, Carlo; Sabatini, Alessia et al

in Antimicrobial agents and chemotherapy (2016), 60(4), 2366-72

Two laboratory mutants of NDM-1 were generated by replacing the isoleucine at position 35 with threonine and serine residues: the NDM-1(I35T)and NDM-1(I35S)enzymes. These mutants were well characterized ... [more ▼]

Two laboratory mutants of NDM-1 were generated by replacing the isoleucine at position 35 with threonine and serine residues: the NDM-1(I35T)and NDM-1(I35S)enzymes. These mutants were well characterized, and their kinetic parameters were compared with those of the NDM-1 wild type. Thekcat,Km, andkcat/Kmvalues calculated for the two mutants were slightly different from those of the wild-type enzyme. Interestingly, thekcat/Kmof NDM-1(I35S)for loracarbef was about 14-fold higher than that of NDM-1. Far-UV circular dichroism (CD) spectra of NDM-1 and NDM-1(I35T)and NDM-1(I35S)enzymes suggest local structural rearrangements in the secondary structure with a marked reduction of alpha-helix content in the mutants. [less ▲]

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See detailStudy of a Natural Mutant SHV-Type beta-Lactamase, SHV-104, from Klebsiella pneumoniae
Achour, Nahed Ben; Belhadj, Omrane; Galleni, Moreno ULg et al

in International journal of microbiology (2014), 2014

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See detailR164H and V240H replacements by site-directed mutagenesis of TEM-149 extended-spectrum beta-lactamase: kinetic analysis of TEM-149H240 and TEM-149H164-H240 laboratory mutants.
Perilli, Mariagrazia; Celenza, Giuseppe; Mercuri, Paola ULg et al

in Antimicrobial agents and chemotherapy (2013), 57(2), 1047-9

Two laboratory mutant forms, TEM-149(H240) and TEM-149(H164-H240), of the TEM-149 extended-spectrum beta-lactamase enzyme were constructed by site-directed mutagenesis. TEM-149(H240) and TEM-149(H164-H240 ... [more ▼]

Two laboratory mutant forms, TEM-149(H240) and TEM-149(H164-H240), of the TEM-149 extended-spectrum beta-lactamase enzyme were constructed by site-directed mutagenesis. TEM-149(H240) and TEM-149(H164-H240) were similar in kinetic behavior, except with respect to benzylpenicillin and ceftazidime. Molecular modeling of the two mutant enzymes demonstrated the role of histidine at position 240 in the reduction of the affinity of the enzyme for ceftazidime. [less ▲]

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See detailDifferential proteomic analysis of the response of Stenotrophomonas maltophilia to imipenem
Van Oudenhove, L; De Vriendt, K; Van Beeumen, J et al

in Applied Microbiology and Biotechnology (2012), 95

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See detailFirst detection of a transferable blaCTX-M-14b gene in a Klebsiella pneumoniae clinical isolate from Tunisia and analysis of its genetic context
Ben Achour, Nahed; Power, Pablo; Mercuri, Paola ULg et al

in Annals of Microbiology (2012), 62

Klebsiella pneumoniae ML2508 was isolated from a patient at the surgery unit of the Military Hospital (Hôpital Militaire de Tunis), Tunisia. It was identified as a producer of extended-spectrum β ... [more ▼]

Klebsiella pneumoniae ML2508 was isolated from a patient at the surgery unit of the Military Hospital (Hôpital Militaire de Tunis), Tunisia. It was identified as a producer of extended-spectrum β-lactamases (ESBLs) by the double-disk synergy test. The β-lactamases produced by the strain were characterized by isoelectric focusing, determination of the specific activities against penicillins and cephalosporins, determination of the inhibitory concentration required to inhibit 50% of enzyme activity (IC50), and the inhibition effect of EDTA on putative metallo-β-lactamases. The crude extract of K. pneumoniae ML2508 contains five different β-lactamases with pI 5.5, 7.3, 7.6, 8.1, and 8.6. Only the β-lactamase with pI 8.1 was transferred by transformation and conjugation experiments. Molecular characterization of these genes was performed by PCR and sequencing. The four chromosomal β-lactamases are TEM (pI 5.5), 2 SHV (pI 7.3 and 7.6), and CTX-M-28 (pI 8.6). The β-lactamase with pI 8.1 was encoded byblaCTX-M-14b gene located on a 50-kb highly conjugative plasmid. The study of the genetic context of blaCTX-M-14b was realized by PCR mapping and DNA sequencing. A novel variant of tnpISEcp1 designated ISEcp1C was detected upstream of the gene. [less ▲]

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See detailMolecular characterization of plasmid-encoded ACC-1a4 β-lactamase produced by Salmonella strains isolated from water in a Tunisian hospital
Ben Aissa, Melek; Herteg Fernea, Adriana; Bouraoui, Hanene et al

in Annals of Microbiology (2012), 62

A collection of non-typhoidal Salmonella strains, designated MMB1 to MMB18, resistant to third generation cephalosporins were isolated from water in a Tunisian hospital. Isolates harbored a new blaACC ... [more ▼]

A collection of non-typhoidal Salmonella strains, designated MMB1 to MMB18, resistant to third generation cephalosporins were isolated from water in a Tunisian hospital. Isolates harbored a new blaACC gene located on a small transmissible plasmid of 5 kb. The ACC-1a4 enzyme was produced in Escherichia coli, purified and characterized. Compared to the chromosomal blaACC-1a gene, the blaACC-1a4 exhibit three mutations. We determined the kinetic parameters of our enzyme for a representative series of β-lactam substrates. The ACC-1a4 enzyme was active on penicillins and cephalosporins, nitrocefin and cephalothin being its best tested substrates. This is a real cause for alarm since these mutations showed that the DNA sequence of blaACC is an intermediate between those of blaACC-1a and blaACC-4 and might increase the probability of the appearance and spreading of ACC-4-mediated resistance in the hospital environment [less ▲]

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See detailNovel fragments of clavulanate observed in the structure of the class A b-lactamase from Bacillus licheniformis BS3
Power, Pablo; Mercuri, Paola ULg; Herman, Raphaël ULg et al

in Journal of Antimicrobial Chemotherapy (2012), 67(10), 2379-2387

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See detailEmergence and dominance of CTX-M-15 extended spectrum beta-lactamase among Escherichia coli isolates from children.
Réjiba, S; Mercuri, Paola ULg; Power, P et al

in Microbial Drug Resistance (2011), 17

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See detailMercaptophosphonate Compounds as Broad-Spectrum Inhibitors of the Metallo-β-lactamases
Lassaux, Patricia ULg; Hamel, Matthieu; Gulea, Mihaela et al

in Journal of Medicinal Chemistry (2010), 53

In this paper, we investigated the inhibitory effect of mercaptophosphonate derivatives against the three subclasses of MBLs (B1, B2, and B3). All 14 tested mercaptophosphonates, with the exception of one ... [more ▼]

In this paper, we investigated the inhibitory effect of mercaptophosphonate derivatives against the three subclasses of MBLs (B1, B2, and B3). All 14 tested mercaptophosphonates, with the exception of one, behaved as competitive inhibitors for the three subclasses. <br />Apart from two compounds, all the mercaptophosphonates tested exhibit a good inhibitory effect on the subclass B2 MBL CphA with low inhibition constants (Ki<15 μM). Interestingly, compound 18 turned out to be a potent broad spectrum MBL inhibitor. <br />The crystallographic structures of the CphA-10a and CphA-18 complexes indicated that the sulfur atom of 10a and the phosphonato group of 18 interact with the Zn2þ ion, respectively. Molecular modeling studies of the interactions between two compounds and the VIM-4 (B1), CphA (B2), and FEZ-1 (B3) enzymes brought to light different binding modes depending on the enzyme and the inhibitor, consistent with the crystallographic structures. [less ▲]

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See detailIdentification of bla(IMP-22) in Pseudomonas spp. in urban wastewater and nosocomial environments: biochemical characterization of a new IMP metallo-enzyme variant and its genetic location.
Pellegrini, Cristina; Mercuri, Paola ULg; Celenza, Giuseppe et al

in The Journal of antimicrobial chemotherapy (2009), 63(5), 901-8

OBJECTIVES: The aim of the study was the biochemical characterization of a new variant of the metallo-beta-lactamase, IMP-22. Moreover, the genetic environment of the bla(IMP-22) gene was investigated in ... [more ▼]

OBJECTIVES: The aim of the study was the biochemical characterization of a new variant of the metallo-beta-lactamase, IMP-22. Moreover, the genetic environment of the bla(IMP-22) gene was investigated in Pseudomonas fluorescens and Pseudomonas aeruginosa collected from urban wastewater and a teaching hospital in L'Aquila, Italy. METHODS: Molecular characterization of genetic elements was carried out by PCR and DNA sequencing methods. The new enzyme was purified from recombinant Escherichia coli BL21(DE)Rosetta/pBC-SK/IMP-22. Steady-state kinetic parameters (K(m) and V(max)) were determined for a large pattern of substrates. RESULTS: A new IMP metallo-beta-lactamase gene was found in a class 1 integron and in one case, in a plasmid of Pseudomonas spp. The bla(IMP-22) encodes for a pre-protein of 246 amino acids and the N-terminus of the mature beta-lactamase (NH(2)-PDLK) was also determined. The molecular mass and pI were 24 930 Da and 6.2, respectively. On the basis of the kinetic parameters calculated (K(m) and V(max)), IMP-22 was found to hydrolyse narrow- and extended-spectrum beta-lactams. Enzyme activity was found to be inhibited by metal chelators such as EDTA, 1,10-o-phenathroline and dipicolinic acid with an IC(50) of 800, 750 and 300 microM, respectively. CONCLUSIONS: The finding of the bla(IMP-22) gene in P. fluorescens environmental strains and P. aeruginosa clinical isolate suggests the ongoing spread of bla(MBL) genes in several bacterial species and in different environments. [less ▲]

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See detailFirst detection of CTX-M-28 in a Tunisian hospital from a cefotaxime-resistant Klebsiella pneumoniae strain.
Ben Achour, N.; Mercuri, Paola ULg; Power, P. et al

in Pathologie-biologie (2009), 57(5), 343-8

A cefotaxime-resistant Klebsiella pneumoniae ML4313 was obtained from a patient from intensive care unit of Military hospital in Tunisia. This strain was resistant to beta-lactams, aminoglycosides ... [more ▼]

A cefotaxime-resistant Klebsiella pneumoniae ML4313 was obtained from a patient from intensive care unit of Military hospital in Tunisia. This strain was resistant to beta-lactams, aminoglycosides, quinolones and phenicols, and tetracyclines. It was identified as producer of extended-spectrum beta-lactamases (ESBL) by double-disk synergy test between amoxicillin-clavulanate and cefotaxime, ceftriaxone, ceftazidime and aztreonam. The ESBL was identified as CTX-M-28 by sequencing of PCR products and by isoelectric focusing. The ESBL resistance was transferred by a 50kb plasmid. CTX-M-28 is closely related to CTX-M-15. This is the first description of this enzyme in Tunisia. [less ▲]

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See detailCharacterization of a novel extended-spectrum TEM-type beta-lactamase, TEM-164, in a clinical strain of Klebsiella pneumoniae in Tunisia.
Ben Achour, Nahed; Mercuri, Paola ULg; Ben Moussa, Mohamed et al

in Microbial drug resistance (Larchmont, N.Y.) (2009), 15(3), 195-9

Klebsiella pneumoniae ML1708 exhibited a multiresistance phenotype, including resistance to all beta-lactams tested, chloramphenicol, ciprofloxacin, nalidixic acid, tetracycline, and streptomycin. The ... [more ▼]

Klebsiella pneumoniae ML1708 exhibited a multiresistance phenotype, including resistance to all beta-lactams tested, chloramphenicol, ciprofloxacin, nalidixic acid, tetracycline, and streptomycin. The double-disk synergy test was positive. ML1708 harbored a 50 kb conjugative plasmid that encoded a beta-lactamase of pI 5.5. The corresponding bla gene was identified by polymerase chain reaction and sequencing as a bla(TEM) gene. The deduced protein sequence revealed a new variant of TEM-1 beta-lactamase designated TEM-164. TEM-164 contains the unusual following mutations: L40V and I279T. These modifications may result in a change of the pI to 5.5 and hydrolyze cefotaxime and ceftazidime. [less ▲]

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See detailCefotaxime and ceftriaxon resistant Klebsiella pneumoniae associated with SHV-11 hyperproduction
Ben Achour, Nahed; Mercuri, Paola ULg; Belhadj, Chrifa et al

in Annals of Microbiology (2008), 5(4), 727-730

Klebsiella pneumoniae ML0306 was isolated from a patient in the intensive care unit of the Military hospital of Tunis in Tunisia. The strain was resistant to β-lactams, aminoglycosides, quinolones ... [more ▼]

Klebsiella pneumoniae ML0306 was isolated from a patient in the intensive care unit of the Military hospital of Tunis in Tunisia. The strain was resistant to β-lactams, aminoglycosides, quinolones, phenicols and tetracyclines. Crude extract from the isolate showed a broad-substrate profile by hydrolyzing benzylpenicillin, ampicillin, cloxacilline, cephalothin, cefotaxime and ceftriaxone but not ceftazidime, cefoxitin, cefpirome, imipinem and aztreonam. The isolate was identified as a producer of pI 7.6 β-lactamase. Sequencing of the β-lactamase gene showed that it coded for a penicillinase SHV-11. This is the first description of this enzyme in Tunisia. The gene encoding this enzyme was located on the chromosome and a 50 kb conjugative plasmid. The overproduction of SHV-11 was involved in the wading of the hydrolytic spectrum of the strain. [less ▲]

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See detailCharacterization of the cattle serum antibody responses against TEM beta-lactamase and the nonimmunogenic Escherichia coli heat-stable enterotoxin (STaI)
Zervosen, Astrid ULg; Saegerman, Claude ULg; Antoniotti, Ingrid et al

in FEMS Immunology & Medical Microbiology (2008), 54(3), 319-329

In order to test the use of a subunit recombinant vaccine for its capacity to induce antibodies against the nonimmunogenic heat-stable enterotoxin STa from Escherichia coli and the TEM-1 beta-lactamase ... [more ▼]

In order to test the use of a subunit recombinant vaccine for its capacity to induce antibodies against the nonimmunogenic heat-stable enterotoxin STa from Escherichia coli and the TEM-1 beta-lactamase, cattle were immunized with a hybrid protein created by insertion of the STa sequence at position 197 of the TEM-1 beta-lactamase. Specific anti-STa IgG and IgG1 antibodies were detected at low levels, while no IgG2 antibodies were detected. In contrast, high levels of the different anti-TEM IgG subtypes were detected in cattle sera. In addition, beta-lactamase activity was inhibited by the sera. The presence of antibodies against STa and TEM-1 beta-lactamase was assessed in sera from 366 cattle taken from the field. No significant level of IgGs against the toxin or the TEM-1 was detected. A comparison of the antibody level between the immunized and the nonimmunized animals clearly demonstrated that STa was not able to induce a significant level of antibodies in the vaccinated animals. In contrast, a strong antibody response against TEM-1 beta-lactamase was demonstrated. [less ▲]

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See detailSynthesis of copolymer brushes endowed with adhesion to stainless steel surfaces and antibacterial properties by controlled nitroxide-mediated radical polymerization
Ignatova, Miléna; Voccia, Samuel; Gilbert, Bernard ULg et al

in Langmuir (2004), 20(24), 10718-10726

Novel copolymer brushes have been synthesized by a two-step "grafting from" method that consists of the electrografting of poly(2-phenyl-2-(2,2,6,6-tetramethyl-piperidin-1-yloxy)-ethylacrylate) onto ... [more ▼]

Novel copolymer brushes have been synthesized by a two-step "grafting from" method that consists of the electrografting of poly(2-phenyl-2-(2,2,6,6-tetramethyl-piperidin-1-yloxy)-ethylacrylate) onto stainless steel, followed by the nitroxide-mediated radical polymerization of 2-(dimethylamino ethyl)acrylate and styrene or n-butyl acrylate, initiated from the electrografted polyacrylate chains. The grafted copolymers were quaternized in order to endow them with antibacterial properties. Peeling tests have confirmed the strong adhesion of the grafted copolymer onto the stainless steel substrate. Quartz crystal microbalance experiments have proven that fibrinogen adhesion is lower on the hydrophilic quaternized films compared to the nonionic counterpart. Such quaternized copolymers exhibit significant antibacterial activity against the Gram-positive bacteria S. aureus and the Gram-negative bacteria E. coli. [less ▲]

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See detailProbing the specificity of the subclass B3 FEZ-1 metallo-beta-lactamase by site-directed mutagenesis
Mercuri, Paola ULg; Garcia-Saez, I.; De Vriendt, K. et al

in Journal of Biological Chemistry (2004), 279(32), 33630-33638

The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella) gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in penicillins, cephalosporins, and carbapenems. FEZ ... [more ▼]

The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella) gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in penicillins, cephalosporins, and carbapenems. FEZ-1 has been extensively studied using kinetic, computational modeling and x-ray crystallography. In an effort to probe residues potentially involved in substrate binding and zinc binding, five site-directed mutants of FEZ-1 (H121A, Y156A, S221A, N225A, and Y228A) were prepared and characterized using metal analyses and steady state kinetics. The activity of H121A is dependent on zinc ion concentration. The H121A monozinc form is less active than the dizinc form, which exhibits an activity similar to that of the wild type enzyme. Tyr156 is not essential for binding and hydrolysis of the substrate. Substitution of residues Ser221 and Asn225 modifies the substrate profile by selectively decreasing the activity against carbapenems. The Y228A mutant is inhibited by the product formed upon hydrolysis of cephalosporins. A covalent bond between the side chain of Cys200 and the hydrolyzed cephalosporins leads to the formation of an inactive and stable complex. [less ▲]

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See detailUpdate of the standard numbering scheme for class B beta-lactamases
Garau, G.; Garcia-Saez, I.; Bebrone, Carine ULg et al

in Antimicrobial Agents and Chemotherapy (2004), 48(7), 2347-2349

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See detailThree-dimensional structure of FEZ-1, a monomeric subclass B3 metallo-beta-lactamase from Fluoribacter gormanii, in native form and in complex with D-captopril
Garcia-Saez, I.; Mercuri, Paola ULg; Papamicael, C. et al

in Journal of Molecular Biology (2003), 325(4), 651-660

The beta-lactamases are involved in bacterial resistance to penicillin and related compounds. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are thus becoming of major ... [more ▼]

The beta-lactamases are involved in bacterial resistance to penicillin and related compounds. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are thus becoming of major clinical importance. The structures of the Zn-beta-lactamase from Fluoribacter gormanii (FEZ-1) in the native and in the complex form are reported here. FEZ-I is a monomeric enzyme, which possesses two zinc-binding sites. These structures are discussed in comparison with those of the tetrameric L1 enzyme produced by Stenotrophomonas maltophilia. From this analysis, amino acids involved in the oligomerization of L1 are clearly identified. Despite the similarity in fold, the active site of FEZ-1 was found to be significantly different. Two residues, which were previously implicated in function, are not present in L1 or in FEZ-1. The broad-spectrum substrate profile of Zn-beta-lactamases arises from the rather wide active-site cleft, where various P-lactam compounds can be accommodated. (C) 2003 Elsevier Science Ltd. All rights reserved. [less ▲]

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