References of "Mingeot-Leclercq, MP"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailThe Pseudomonas aeruginosa membranes: A target for a new amphiphilic aminoglycoside derivative?
Ouberai, M.; El Garch, F.; Bussiere, A. et al

in Biochimica et biophysica acta (2011)

Aminoglycosides are among the most potent antimicrobials to eradicate Pseudomonas aeruginosa. However, the emergence of resistance has clearly led to a shortage of treatment options, especially for ... [more ▼]

Aminoglycosides are among the most potent antimicrobials to eradicate Pseudomonas aeruginosa. However, the emergence of resistance has clearly led to a shortage of treatment options, especially for critically ill patients. In the search for new antibiotics, we have synthesized derivatives of the small aminoglycoside, neamine. The amphiphilic aminoglycoside 3',4',6-tri-2-naphtylmethylene neamine (3',4',6-tri-2NM neamine) has appeared to be active against sensitive and resistant P. aeruginosa strains as well as Staphylococcus aureus strains (Baussanne et al., 2010). To understand the molecular mechanism involved, we determined the ability of 3',4',6-tri-2NM neamine to alter the protein synthesis and to interact with the bacterial membranes of P. aeruginosa or models mimicking these membranes. Using atomic force microscopy, we observed a decrease of P. aeruginosa cell thickness. In models of bacterial lipid membranes, we showed a lipid membrane permeabilization in agreement with the deep insertion of 3',4',6-tri-2NM neamine within lipid bilayer as predicted by modeling. This new amphiphilic aminoglycoside bound to lipopolysaccharides and induced P. aeruginosa membrane depolarization. All these effects were compared to those obtained with neamine, the disubstituted neamine derivative (3',6-di-2NM neamine), conventional aminoglycosides (neomycin B and gentamicin) as well as to compounds acting on lipid bilayers like colistin and chlorhexidine. All together, the data showed that naphthylmethyl neamine derivatives target the membrane of P. aeruginosa. This should offer promising prospects in the search for new antibacterials against drug- or biocide-resistant strains. [less ▲]

Detailed reference viewed: 20 (2 ULg)
Full Text
Peer Reviewed
See detailInteractions Of Ciprofloxacin With Dppc And Dppg: Fluorescence Anisotropy, Atr-Ftir And P-31 Nmr Spectroscopies And Conformational Analysis
Bensikaddour, H.; Snoussi, K.; Lins, Laurence ULg et al

in Biochimica et Biophysica Acta-Biomembranes (2008), 1778(11), 2535-43

The interactions between a drug and lipids may be critical for the pharmacological activity. We previously showed that the ability of a fluoroquinolone antibiotic, ciprofloxacin, to induce disorder and ... [more ▼]

The interactions between a drug and lipids may be critical for the pharmacological activity. We previously showed that the ability of a fluoroquinolone antibiotic, ciprofloxacin, to induce disorder and modify the orientation of the acyl chains is related to its propensity to be expelled from a monolayer upon compression [1]. Here, we compared the binding of ciprofloxacin on DPPC and DPPG liposomes (or mixtures of phospholipids [DOPC:DPPC], and [DOPC:DPPG]) using quasi-elastic light scattering and steady-state fluorescence anisotropy. We also investigated ciprofloxacin effects on the transition temperature (T(m)) of lipids and on the mobility of phosphate head groups using Attenuated Total Reflection Fourier Transform Infrared-Red Spectroscopy (ATR-FTIR) and (31)P Nuclear Magnetic Resonance (NMR) respectively. In the presence of ciprofloxacin we observed a dose-dependent increase of the size of the DPPG liposomes whereas no effect was evidenced for DPPC liposomes. The binding constants K(app) were in the order of 10(5) M(-1) and the affinity appeared dependent on the negative charge of liposomes: DPPG>DOPC:DPPG (1:1; M:M)>DPPC>DOPC:DPPC (1:1; M:M). As compared to the control samples, the chemical shift anisotropy (Deltasigma) values determined by (31)P NMR showed an increase of 5 and 9 ppm for DPPC:CIP (1:1; M:M) and DPPG:CIP (1:1; M:M) respectively. ATR-FTIR experiments showed that ciprofloxacin had no effect on the T(m) of DPPC but increased the order of the acyl chains both below and above this temperature. In contrast, with DPPG, ciprofloxacin induced a marked broadening effect on the transition with a decrease of the acyl chain order below its T(m) and an increase above this temperature. Altogether with the results from the conformational analysis, these data demonstrated that the interactions of ciprofloxacin with lipids depend markedly on the nature of their phosphate head groups and that ciprofloxacin interacts preferentially with anionic lipid compounds, like phosphatidylglycerol, present at a high content in these membranes. [less ▲]

Detailed reference viewed: 17 (2 ULg)
Full Text
Peer Reviewed
See detailProbing Peptide-Membrane Interactions Using Afm
Brasseur, Robert ULg; Deleu, Magali ULg; Mingeot-Leclercq, Mp. et al

in Surface and Interface Analysis [=SIA] (2008), 40(3-4), 151-156

Atomic force microscopy (AFM) has become a powerful addition to the range of instruments available to probe the organization of lipid monolayers and bilayers. Currently, AFM is the only tool that can ... [more ▼]

Atomic force microscopy (AFM) has become a powerful addition to the range of instruments available to probe the organization of lipid monolayers and bilayers. Currently, AFM is the only tool that can provide nanoscale topographic images of supported lipid membranes under physiological conditions, enabling researchers to resolve their detailed structure and to monitor their interaction with drugs, peptides and proteins. Here, we survey recent data obtained by our research groups that demonstrate the power of the technique for exploring peptide–membrane interactions, with an emphasis on microbial lipopeptides and on tilted peptides. [less ▲]

Detailed reference viewed: 8 (0 ULg)
Full Text
Peer Reviewed
See detailDecrease Of Elastic Moduli Of Dopc Bilayers Induced By A Macrolide Antibiotic, Azithromycin
Fa, N.; Lins, Laurence ULg; Courtoy, Pj. et al

in Biochimica et Biophysica Acta-Biomembranes (2007), 1768(7), 1830-8

The elastic properties of membrane bilayers are key parameters that control its deformation and can be affected by pharmacological agents. Our previous atomic force microscopy studies revealed that the ... [more ▼]

The elastic properties of membrane bilayers are key parameters that control its deformation and can be affected by pharmacological agents. Our previous atomic force microscopy studies revealed that the macrolide antibiotic, azithromycin, leads to erosion of DPPC domains in a fluid DOPC matrix [A. Berquand, M. P. Mingeot-Leclercq, Y. F. Dufrene, Real-time imaging of drug-membrane interactions by atomic force microscopy, Biochim. Biophys. Acta 1664 (2004) 198-205.]. Since this observation could be due to an effect on DOPC cohesion, we investigated the effect of azithromycin on elastic properties of DOPC giant unilamellar vesicles (GUVs). Microcinematographic and morphometric analyses revealed that azithromycin addition enhanced lipid membranes fluctuations, leading to eventual disruption of the largest GUVs. These effects were related to change of elastic moduli of DOPC, quantified by the micropipette aspiration technique. Azithromycin decreased both the bending modulus (k(c), from 23.1+/-3.5 to 10.6+/-4.5 k(B)T) and the apparent area compressibility modulus (K(app), from 176+/-35 to 113+/-25 mN/m). These data suggested that insertion of azithromycin into the DOPC bilayer reduced the requirement level of both the energy for thermal fluctuations and the stress to stretch the bilayer. Computer modeling of azithromycin interaction with DOPC bilayer, based on minimal energy, independently predicted that azithromycin (i) inserts at the interface of phospholipid bilayers, (ii) decreases the energy of interaction between DOPC molecules, and (iii) increases the mean surface occupied by each phospholipid molecule. We conclude that azithromycin inserts into the DOPC lipid bilayer, so as to decrease its cohesion and to facilitate the merging of DPPC into the DOPC fluid matrix, as observed by atomic force microscopy. These investigations, based on three complementary approaches, provide the first biophysical evidence for the ability of an amphiphilic antibiotic to alter lipid elastic moduli. This may be an important determinant for drug: lipid interactions and cellular pharmacology. [less ▲]

Detailed reference viewed: 4 (1 ULg)
Full Text
Peer Reviewed
See detailThe Biologically Important Surfactin Lipopeptide Induces Nanoripples In Supported Lipid Bilayers
Brasseur, Robert ULg; Braun, N.; El Kirat, K. et al

in Langmuir (2007), 23(19), 9769-72

Under specific conditions, lipid membranes form ripple phases with intriguing nanoscale undulations. Here, we show using in situ atomic force microscopy (AFM) that the biologically important surfactin ... [more ▼]

Under specific conditions, lipid membranes form ripple phases with intriguing nanoscale undulations. Here, we show using in situ atomic force microscopy (AFM) that the biologically important surfactin lipopeptide induces nanoripples of 30 nm periodicity in dipalmitoyl phosphatidylcholine (DPPC) bilayers at 25 degrees (i.e. well below the pretransition temperature of DPPC). Whereas most undulations formed the classical straight orientation with characteristic angle changes of 120 degrees , some of them also displayed unusual circular orientations. Strikingly, ripple structures were formed at 15% surfactin but were rarely or never observed at 5 and 30% surfactin, emphasizing the important role played by the surfactin concentration. Theoretical simulations corroborated the AFM data by revealing the formation of stable surfactin/lipid assemblies with positive curvature. [less ▲]

Detailed reference viewed: 9 (0 ULg)
Full Text
Peer Reviewed
See detailEffect Of The Antibiotic Azithromycin On Thermotropic Behavior Of Dopc Or Dppc Bilayers
Fa, N.; Ronkart, Sébastien ULg; Schanck, A. et al

in Chemistry and Physics of Lipids (2006), 144(1),

Detailed reference viewed: 10 (1 ULg)
Full Text
Peer Reviewed
See detailPiracetam Inhibits The Lipid-Destabilising Effect Of The Amyloid Peptide A Beta C-Terminal Fragment
Mingeot-Leclercq, Mp.; Lins, Laurence ULg; Bensliman, M. et al

in Biochimica et Biophysica Acta-Biomembranes (2003), 1609(1), 28-38

Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor protein (APP), implicated in the pathogenesis of Alzheimer's disease. The hypothesis that interactions between Abeta ... [more ▼]

Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor protein (APP), implicated in the pathogenesis of Alzheimer's disease. The hypothesis that interactions between Abeta aggregates and neuronal membranes play an important role in toxicity has gained some acceptance. Previously, we showed that the C-terminal domain (e.g. amino acids 29-42) of Abeta induces membrane permeabilisation and fusion, an effect which is related to the appearance of non-bilayer structures. Conformational studies showed that this peptide has properties similar to those of the fusion peptide of viral proteins i.e. a tilted penetration into membranes. Since piracetam interacts with lipids and has beneficial effects on several symptoms of Alzheimer's disease, we investigated in model membranes the ability of piracetam to hinder the destabilising effect of the Abeta 29-42 peptide. Using fluorescence studies and 31P and 2H NMR spectroscopy, we have shown that piracetam was able to significantly decrease the fusogenic and destabilising effect of Abeta 29-42, in a concentration-dependent manner. While the peptide induced lipid disorganisation and subsequent negative curvature at the membrane-water interface, the conformational analysis showed that piracetam, when preincubated with lipids, coats the phospholipid headgroups. Calculations suggest that this prevents appearance of the peptide-induced curvature. In addition, insertion of molecules with an inverted cone shape, like piracetam, into the outer membrane leaflet should make the formation of such structures energetically less favourable and therefore decrease the likelihood of membrane fusion. [less ▲]

Detailed reference viewed: 7 (0 ULg)
Full Text
Peer Reviewed
See detailCellular Uptake Of Antennapedia Penetratin Peptides Is A Two-Step Process In Which Phase Transfer Precedes A Tryptophan-Dependent Translocation
Dom, G.; Shaw-Jackson, C.; Matis, C. et al

in Nucleic Acids Research (2003), 31(2), 556-61

Several homeodomains and homeodomain-containing proteins enter live cells through a receptor- and energy-independent mechanism. Translocation through biological membranes is conferred by the third alpha ... [more ▼]

Several homeodomains and homeodomain-containing proteins enter live cells through a receptor- and energy-independent mechanism. Translocation through biological membranes is conferred by the third alpha-helix of the homeodomain, also known as Penetratin. Biophysical studies demonstrate that entry of Penetratin into cells requires its binding to surface lipids but that binding and translocation are differentially affected by modifications of some physico-chemical properties of the peptide, like helical amphipathicity or net charge. This suggests that the plasma membrane lipid composition affects the internalization of Penetratin and that internalization requires both lipid binding and other specific properties. Using a phase transfer assay, it is shown that negatively charged lipids promote the transfer of Penetratin from a hydrophilic into a hydrophobic environment, probably through charge neutralization. Accordingly, transfer into a hydrophobic milieu can also be obtained in the absence of negatively charged lipids, by the addition of DNA oligonucleotides. Strikingly, phase transfer by charge neutralization was also observed with a variant peptide of same charge and hydrophobicity in which the tryptophan at position 6 was replaced by a phenylalanine. However, Penetratin, but not its mutant version, is internalized by live cells. This underscores that charge neutralization and phase transfer represent only a first step in the internalization process and that further crossing of a biological membrane necessitates the critical tryptophan residue at position 6. [less ▲]

Detailed reference viewed: 10 (1 ULg)
Full Text
Peer Reviewed
See detailCell Handling, Membrane-Binding Properties, And Membrane-Penetration Modeling Approaches Of Pivampicillin And Phthalimidomethylampicillin, Two Basic Esters Of Ampicillin, In Comparison With Chloroquine And Azithromycin
Chanteux, H.; Paternotte, I.; Mingeot-Leclercq, Mp. et al

in Pharmaceutical Research (2003), 20(4), 624-31

PURPOSE: The purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with ... [more ▼]

PURPOSE: The purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with lysosomotropic drugs (chloroquine, azithromycin). METHODS: Cell culture studies (J774 macrophages) were undertaken to study uptake and release kinetics and to assess the influence of concentration, pH, proton ionophore (monensin), and MRP and P-gp inhibitors (probenecid, gemfibrozil, cyclosporin A, GF 120918). Equilibrium dialysis with liposomes were performed to directly asses the extent of drug binding to bilayers. Conformational analysis modeling of the drug penetration in bilayers was conducted to rationalize the experimental observations. RESULTS: PIVA and PIMA showed properties in almost complete contrast with those of chloroquine and azithromycin, i.e., fast apparent accumulation and fast release at 4 degrees C as well as at 37 degrees C, saturation of uptake (apparent Kd 40 microM), no influence of monensin, MRP, or P-gp inhibitors; tight binding to liposomes (Kd approx. 40 microM); and sharp increase in calculated free energy when forced in the hydrophobic domain. CONCLUSIONS: Although they are weak organic bases, PIVA and PIMA show none of the properties of lysosomotropic agents. We hypothesize that they remain locked onto the pericellular membrane and may never penetrate cells as such in significant amounts. [less ▲]

Detailed reference viewed: 3 (0 ULg)
Full Text
Peer Reviewed
See detailThe Macrolide Antibiotic Azithromycin Interacts With Lipids And Affects Membrane Organization And Fluidity: Studies On Langmuir-Blodgett Monolayers, Liposomes And J774 Macrophages
Tyteca, D.; Schanck, A.; Dufrene, Yf. et al

in Journal of Membrane Biology (2003), 192(3), 203-215

Detailed reference viewed: 12 (1 ULg)
Full Text
Peer Reviewed
See detailMembrane Destabilization Induced By Beta-Amyloid Peptide 29-42: Importance Of The Amino-Terminus
Mingeot-Leclercq, Mp.; Lins, Laurence ULg; Bensliman, M. et al

in Chemistry and Physics of Lipids (2002), 120(1-2), 57-74

Increasing evidence implicates interactions between Abeta-peptides and membrane lipids in Alzheimer's disease. To gain insight into the potential role of the free amino group of the N-terminus of Abeta29 ... [more ▼]

Increasing evidence implicates interactions between Abeta-peptides and membrane lipids in Alzheimer's disease. To gain insight into the potential role of the free amino group of the N-terminus of Abeta29-42 fragment in these processes, we have investigated the ability of Abeta29-42 unprotected and Abeta29-42 N-protected to interact with negatively-charged liposomes and have calculated the interaction with membrane lipids by conformational analysis. Using vesicles mimicking the composition of neuronal membranes, we show that both peptides have a similar capacity to induce membrane fusion and permeabilization. The fusogenic effect is related to the appearance of non-bilayer structures where isotropic motions occur as shown by 31P and 2H NMR studies. The molecular modeling calculations confirm the experimental observations and suggest that lipid destabilization could be due to the ability of both peptides to adopt metastable positions in the presence of lipids. In conclusion, the presence of a free or protected (acetylated) amino group in the N-terminus of Abeta29-42 is therefore probably not crucial for destabilizing properties of the C-terminal fragment of Abeta peptides. [less ▲]

Detailed reference viewed: 7 (1 ULg)
Full Text
Peer Reviewed
See detailExperimental And Conformational Analyses Of Interactions Between Butenafine And Lipids
Mingeot-Leclercq, Mp.; Gallet, X.; Flore, Christelle ULg et al

in Antimicrobial Agents and Chemotherapy (2001), 45(12), 3347-54

Butenafine (N-4-tert-butylbenzyl-N-methyl-1-naphtalenemethylamine hydrochloride) is an antifungal agent of the benzylamine class that has excellent therapeutic efficacy and a remarkably long duration of ... [more ▼]

Butenafine (N-4-tert-butylbenzyl-N-methyl-1-naphtalenemethylamine hydrochloride) is an antifungal agent of the benzylamine class that has excellent therapeutic efficacy and a remarkably long duration of action when applied topically to treat various mycoses. Given the lipophilic nature of the molecule, efficacy may be related to an interaction with cell membrane phospholipids and permeabilization of the fungal cell wall. Similarly, high lipophilicity could account for the long duration of action, since fixation to lipids in cutaneous tissues might allow them to act as local depots for slow release of the drug. We have therefore used computer-assisted conformational analysis to investigate the interaction of butenafine with lipids and extended these observations with experimental studies in vitro using liposomes. Conformational analysis of mixed monolayers of phospholipids with the neutral and protonated forms of butenafine highlighted a possible interaction with both the hydrophilic and hydrophobic domains of membrane phospholipids. Studies using liposomes demonstrated that butenafine increases membrane fluidity [assessed by fluorescence polarization of 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenylhexatriene] and membrane permeability (studied by release of calcein from liposomes). The results show, therefore, that butenafine readily interacts with lipids and is incorporated into membrane phospholipids. These findings may help explain the excellent antifungal efficacy and long duration of action of this drug when it is used as a topical antifungal agent in humans. [less ▲]

Detailed reference viewed: 7 (0 ULg)
See detailLysosomal phospholipases inhibition by emetine, strychnopentamine and usambarensine
Quetin-Leclercq, Joelle; Schomer, G; Van Bambeke, F et al

Poster (1999)

Detailed reference viewed: 3 (0 ULg)
Full Text
Peer Reviewed
See detailInteractions Of Macrolide Antibiotics (Erythromycin A, Roxithromycin, Erythromycylamine [Dirithromycin], And Azithromycin) With Phospholipids: Computer-Aided Conformational Analysis And Studies On Acellular And Cell Culture Models
Montenez, Jp.; Van Bambeke, F.; Piret, J. et al

in Toxicology and Applied Pharmacology (1999), 156(2), 129-40

The potential of 14/15 membered macrolides to cause phospholipidosis has been prospectively assessed, and structure-effects examined, using combined experimental and conformational approaches. Biochemical ... [more ▼]

The potential of 14/15 membered macrolides to cause phospholipidosis has been prospectively assessed, and structure-effects examined, using combined experimental and conformational approaches. Biochemical studies demonstrated drug binding to phosphatidylinositol-containing liposomes and inhibition of the activity of lysosomal phospholipase A1 toward phosphatidylcholine included in the bilayer, in close correlation with the number of cationic groups carried by the drugs (erythromycin A </= roxithromycin < erythromycylamine </= azithromycin). In cultured cells (fibroblasts), phospholipidosis (affecting all major phospholipids except sphingomyelin) was observed after 3 days with the following ranking: erythromycin A </= roxithromycin < erythromycylamine < azithromycin (roxithromycin could, however, not be studied in detail due to intrinsic toxicity). The difference between erythromycylamine and azithromycin was accounted for by the lower cellular accumulation of erythromycylamine. In parallel, based on a methodology developed and validated to study drug-membrane interactions, the conformational analyses revealed that erythromycin A, roxithromycin, erythromycylamine, and azithromycin penetrate into the hydrophobic domain of a phosphatidylinositol monolayer through their desosamine and cladinose moieties, whereas their macrocycle is found close to the interface. This position allows the aminogroups carried by the macrocycle of the diaminated macrolides (erythromycylamine and azithromycin) to come into close contact with the negatively charged phosphogroup of phosphatidylinositol, whereas the amine located on the C-3 of the desosamine, common to all four drugs, is located at a greater distance from this phosphogroup. Our study suggests that all macrolides have the potential to cause phospholipidosis but that this effect is modulated by toxicodynamic and toxicokinetic parameters related to the drug structure and mainly to their cationic character. [less ▲]

Detailed reference viewed: 18 (0 ULg)