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Article ; Online: Surface properties and bacterial adhesion on polyurethane central catheters: Impact of ethanol lock solution.

Khzam, A / Saunier, J / Guilbaud, M / Herry, J M / Dazzi, A / Tortolano, L / Carpentier, L / Mignot, A / Yagoubi, N

Biomaterials advances

2023 Volume 146, Page(s) 213281

Abstract: It was shown in the literature that ethanol locks have a positive effect on preventing catheter-related infections in patients with central venous catheters without causing any microbial resistance. However, ethanol is known to interact with ... ...

Abstract	It was shown in the literature that ethanol locks have a positive effect on preventing catheter-related infections in patients with central venous catheters without causing any microbial resistance. However, ethanol is known to interact with polyurethanes. The consequences of this interaction on the catheter surface properties were studied as it can impact the biocompatibility of the material and the adhesion phenomena onto the surface. No physical and chemical degradation was put into evidence, but low molecular weight compounds such as additives were extracted from the catheter bulk or migrated and exudated onto its surface. Nevertheless, as far as bacterial adhesion is concerned, after the catheter was locked and the lock removed, the surface modifications promoted no adhesion.
MeSH term(s)	Humans ; Ethanol/pharmacology ; Polyurethanes ; Bacterial Adhesion ; Central Venous Catheters/adverse effects ; Central Venous Catheters/microbiology ; Catheter-Related Infections/etiology ; Catheter-Related Infections/microbiology
Chemical Substances	Ethanol (3K9958V90M) ; Polyurethanes
Language	English
Publishing date	2023-01-06
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9508
ISSN (online)	2772-9508
DOI	10.1016/j.bioadv.2023.213281
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Article ; Online: Effect of abiotic and biotic factors on Brettanomyces bruxellensis bioadhesion properties.

Le Montagner, Paul / Bakhtiar, Yacine / Miot-Sertier, Cecile / Guilbaud, Morgan / Albertin, Warren / Moine, Virginie / Dols-Lafargue, Marguerite / Masneuf-Pomarède, Isabelle

Food microbiology

2024 Volume 120, Page(s) 104480

Abstract: Biofilms are central to microbial life because of the advantage that this mode of life provides, whereas the planktonic form is considered to be transient in the environment. During the winemaking process, grape must and wines host a wide diversity of ... ...

Abstract	Biofilms are central to microbial life because of the advantage that this mode of life provides, whereas the planktonic form is considered to be transient in the environment. During the winemaking process, grape must and wines host a wide diversity of microorganisms able to grow in biofilm. This is the case of Brettanomyces bruxellensis considered the most harmful spoilage yeast, due to its negative sensory effect on wine and its ability to colonise stressful environments. In this study, the effect of different biotic and abiotic factors on the bioadhesion and biofilm formation capacities of B. bruxellensis was analyzed. Ethanol concentration and pH had negligible effect on yeast surface properties, pseudohyphal cell formation or bioadhesion, while the strain and genetic group factors strongly modulated the phenotypes studied. From a biotic point of view, the presence of two different strains of B. bruxellensis did not lead to a synergistic effect. A competition between the strains was rather observed during biofilm formation which seemed to be driven by the strain with the highest bioadhesion capacity. Finally, the presence of wine bacteria reduced the bioadhesion of B. bruxellensis. Due to biofilm formation, O. oeni cells were observed attached to B. bruxellensis as well as extracellular matrix on the surface of the cells.
MeSH term(s)	Saccharomyces cerevisiae ; Food Microbiology ; Brettanomyces/metabolism ; Wine/microbiology
Language	English
Publishing date	2024-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	50892-5
ISSN	1095-9998 ; 0740-0020
ISSN (online)	1095-9998
ISSN	0740-0020
DOI	10.1016/j.fm.2024.104480
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Article ; Online: Prevalence Study of Cellular Capsid-Specific Immune Responses to AAV2, 4, 5, 8, 9, and rh10 in Healthy Donors.

Xicluna, Rebecca / Avenel, Allan / Vandamme, Céline / Devaux, Marie / Jaulin, Nicolas / Couzinié, Célia / Le Duff, Johanne / Charrier, Alicia / Guilbaud, Mickaël / Adjali, Oumeya / Gernoux, Gwladys

Human gene therapy

2024

Abstract: Recombinant adeno-associated virus (rAAV) vectors appear, more than ever, to be efficient viral vectors ... ...

Abstract	Recombinant adeno-associated virus (rAAV) vectors appear, more than ever, to be efficient viral vectors for
Language	English
Publishing date	2024-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2023.225
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Zs.A 2988: Show issues

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Article ; Online: Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.

Masri, Samer / Carré, Laure / Jaulin, Nicolas / Vandamme, Céline / Couzinié, Célia / Guy-Duché, Aurélien / Dupont, Jean-Baptiste / Pereira, Allwyn / Charpentier, Eric / David, Laurent / Gernoux, Gwladys / Guilbaud, Mickaël / Adjali, Oumeya

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful ... ...

Abstract	Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.
MeSH term(s)	Humans ; Transcriptome ; Monocytes ; Genetic Vectors/genetics ; Adaptive Immunity ; Dendritic Cells ; Dependovirus/genetics
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310447
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Article ; Online: High intraspecific variation of the cell surface physico-chemical and bioadhesion properties in Brettanomyces bruxellensis.

Le Montagner, Paul / Guilbaud, Morgan / Miot-Sertier, Cécile / Brocard, Lysiane / Albertin, Warren / Ballestra, Patricia / Dols-Lafargue, Marguerite / Renouf, Vincent / Moine, Virginie / Bellon-Fontaine, Marie-Noëlle / Masneuf-Pomarède, Isabelle

Food microbiology

2023 Volume 112, Page(s) 104217

Abstract: Brettanomyces bruxellensis is the most damaging spoilage yeast in the wine industry because of its negative impact on the wine organoleptic qualities. The strain persistence in cellars over several years associated with recurrent wine contamination ... ...

Abstract	Brettanomyces bruxellensis is the most damaging spoilage yeast in the wine industry because of its negative impact on the wine organoleptic qualities. The strain persistence in cellars over several years associated with recurrent wine contamination suggest specific properties to persist and survive in the environment through bioadhesion phenomena. In this work, the physico-chemical surface properties, morphology and ability to adhere to stainless steel were studied both on synthetic medium and on wine. More than 50 strains representative of the genetic diversity of the species were considered. Microscopy techniques made it possible to highlight a high morphological diversity of the cells with the presence of pseudohyphae forms for some genetic groups. Analysis of the physico-chemical properties of the cell surface reveals contrasting behaviors: most of the strains display a negative surface charge and hydrophilic behavior while the Beer 1 genetic group has a hydrophobic behavior. All strains showed bioadhesion abilities on stainless steel after only 3 h with differences in the concentration of bioadhered cells ranging from 2.2 × 10
MeSH term(s)	Food Microbiology ; Stainless Steel/analysis ; Brettanomyces/metabolism ; Wine/analysis ; Saccharomyces cerevisiae
Chemical Substances	Stainless Steel (12597-68-1)
Language	English
Publishing date	2023-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	50892-5
ISSN	1095-9998 ; 0740-0020
ISSN (online)	1095-9998
ISSN	0740-0020
DOI	10.1016/j.fm.2023.104217
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Zs.A 4667: Show issues

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Article ; Online: Biofilm-associated persistence of food-borne pathogens.

Bridier, A / Sanchez-Vizuete, P / Guilbaud, M / Piard, J-C / Naïtali, M / Briandet, R

Food microbiology

2015 Volume 45, Issue Pt B, Page(s) 167–178

Abstract: Microbial life abounds on surfaces in both natural and industrial environments, one of which is the food industry. A solid substrate, water and some nutrients are sufficient to allow the construction of a microbial fortress, a so-called biofilm. Survival ...

Abstract	Microbial life abounds on surfaces in both natural and industrial environments, one of which is the food industry. A solid substrate, water and some nutrients are sufficient to allow the construction of a microbial fortress, a so-called biofilm. Survival strategies developed by these surface-associated ecosystems are beginning to be deciphered in the context of rudimentary laboratory biofilms. Gelatinous organic matrices consisting of complex mixtures of self-produced biopolymers ensure the cohesion of these biological structures and contribute to their resistance and persistence. Moreover, far from being just simple three-dimensional assemblies of identical cells, biofilms are composed of heterogeneous sub-populations with distinctive behaviours that contribute to their global ecological success. In the clinical field, biofilm-associated infections (BAI) are known to trigger chronic infections that require dedicated therapies. A similar belief emerging in the food industry, where biofilm tolerance to environmental stresses, including cleaning and disinfection/sanitation, can result in the persistence of bacterial pathogens and the recurrent cross-contamination of food products. The present review focuses on the principal mechanisms involved in the formation of biofilms of food-borne pathogens, where biofilm behaviour is driven by its three-dimensional heterogeneity and by species interactions within these biostructures, and we look at some emergent control strategies.
MeSH term(s)	Bacteria/isolation & purification ; Bacterial Infections/microbiology ; Bacterial Physiological Phenomena ; Biofilms ; Food Microbiology ; Foodborne Diseases/microbiology ; Humans
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	50892-5
ISSN	1095-9998 ; 0740-0020
ISSN (online)	1095-9998
ISSN	0740-0020
DOI	10.1016/j.fm.2014.04.015
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Zs.A 4667: Show issues

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Article ; Online: Novel chemical tyrosine functionalization of adeno-associated virus improves gene transfer efficiency in liver and retina.

Leray, Aurélien / Lalys, Pierre-Alban / Varin, Juliette / Bouzelha, Mohammed / Bourdon, Audrey / Alvarez-Dorta, Dimitri / Pavageau, Karine / Depienne, Sébastien / Marchand, Maia / Mellet, Anthony / Demilly, Joanna / Ducloyer, Jean-Baptiste / Girard, Tiphaine / Fraysse, Bodvaël / Ledevin, Mireille / Guilbaud, Mickaël / Gouin, Sébastien G / Ayuso, Eduard / Adjali, Oumeya /

Larcher, Thibaut / Cronin, Thérèse / Le Guiner, Caroline / Deniaud, David / Mével, Mathieu

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2024 Volume 171, Page(s) 116148

Abstract: Decades of biological and clinical research have led to important advances in recombinant adeno-associated viruses rAAV-based gene therapy gene therapy. However, several challenges must be overcome to fully exploit the potential of rAAV vectors. ... ...

Abstract	Decades of biological and clinical research have led to important advances in recombinant adeno-associated viruses rAAV-based gene therapy gene therapy. However, several challenges must be overcome to fully exploit the potential of rAAV vectors. Innovative approaches to modify viral genome and capsid elements have been used to overcome issues such as unwanted immune responses and off-targeting. While often successful, genetic modification of capsids can drastically reduce vector yield and often fails to produce vectors with properties that translate across different animal species, such as rodents, non-human primates, and humans. Here, we describe a chemical bioconjugation strategy to modify tyrosine residues on AAV capsids using specific ligands, thereby circumventing the need to genetically engineer the capsid sequence. Aromatic electrophilic substitution of the phenol ring of tyrosine residues on AAV capsids improved the in vivo transduction efficiency of rAAV2 vectors in both liver and retinal targets. This tyrosine bioconjugation strategy represents an innovative technology for the engineering of rAAV vectors for human gene therapy.
MeSH term(s)	Animals ; Dependovirus ; Genetic Therapy ; Transduction, Genetic ; Tyrosine/genetics ; Liver ; Retina ; Capsid Proteins/genetics ; Genetic Vectors ; Gene Transfer Techniques
Chemical Substances	Tyrosine (42HK56048U) ; Capsid Proteins
Language	English
Publishing date	2024-01-16
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2024.116148
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Ud II Zs.198: Show issues

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Article ; Online: Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci in mice.

Calabria, Andrea / Cipriani, Carlo / Spinozzi, Giulio / Rudilosso, Laura / Esposito, Simona / Benedicenti, Fabrizio / Albertini, Alessandra / Pouzolles, Marie / Luoni, Mirko / Giannelli, Serena / Broccoli, Vania / Guilbaud, Mickael / Adjali, Oumeya / Taylor, Naomi / Zimmermann, Valérie S / Montini, Eugenio / Cesana, Daniela

Blood

2023 Volume 141, Issue 19, Page(s) 2316–2329

Abstract: Adeno-associated virus (AAV) vectors have been successfully exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector, but it has been shown to integrate within the host cell genome after ... ...

Abstract	Adeno-associated virus (AAV) vectors have been successfully exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector, but it has been shown to integrate within the host cell genome after the generation of double-strand DNA breaks or nicks. Although AAV integration raises some safety concerns, it can also provide therapeutic benefit; the direct intrathymic injection of an AAV harboring a therapeutic transgene results in integration in T-cell progenitors and long-term T-cell immunity. To assess the mechanisms of AAV integration, we retrieved and analyzed hundreds of AAV integration sites from lymph node-derived mature T cells and compared these with liver and brain tissue from treated mice. Notably, we found that although AAV integrations in the liver and brain were distributed across the entire mouse genome, >90% of the integrations in T cells were clustered within the T-cell receptor α, β, and γ genes. More precisely, the insertion mapped to DNA breaks created by the enzymatic activity of recombination activating genes (RAGs) during variable, diversity, and joining recombination. Our data indicate that RAG activity during T-cell receptor maturation induces a site-specific integration of AAV genomes and opens new therapeutic avenues for achieving long-term AAV-mediated gene transfer in dividing cells.
MeSH term(s)	Mice ; Animals ; Genetic Vectors/genetics ; Transgenes ; Plasmids ; Genetic Therapy/methods ; Receptors, Antigen, T-Cell/genetics ; Dependovirus/genetics ; Virus Integration
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022017378
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: AAV8 locoregional delivery induces long-term expression of an immunogenic transgene in macaques despite persisting local inflammation.

Gernoux, Gwladys / Guilbaud, Mickaël / Devaux, Marie / Journou, Malo / Pichard, Virginie / Jaulin, Nicolas / Léger, Adrien / Le Duff, Johanne / Deschamps, Jack-Yves / Le Guiner, Caroline / Moullier, Philippe / Cherel, Yan / Adjali, Oumeya

Molecular therapy. Methods & clinical development

2021 Volume 20, Page(s) 660–674

Abstract: Adeno-associated virus (AAV) vectors are considered efficient vectors for gene transfer, as illustrated by recent successful clinical trials targeting retinal or neurodegenerative disorders. However, limitations as host immune responses to AAV capsid or ... ...

Abstract	Adeno-associated virus (AAV) vectors are considered efficient vectors for gene transfer, as illustrated by recent successful clinical trials targeting retinal or neurodegenerative disorders. However, limitations as host immune responses to AAV capsid or transduction of limited regions must still be overcome. Here, we focused on locoregional (LR) intravenous perfusion vector delivery that allows transduction of large muscular areas and is considered to be less immunogenic than intramuscular (IM) injection. To confirm this hypothesis, we injected 6 cynomolgus monkeys with an AAV serotype 8 (AAV8) vector encoding for the highly immunogenic GFP driven by either a muscle-specific promoter (n = 3) or a cytomegalovirus (CMV) promoter (n = 3). We report that LR delivery allows long-term GFP expression in the perfused limb (up to 1 year) despite the initiation of a peripheral transgene-specific immune response. The analysis of the immune status of the perfused limb shows that LR delivery induces persisting inflammation. However, this inflammation is not sufficient to result in transgene clearance and is balanced by resident regulatory T cells. Overall, our results suggest that LR delivery promotes persisting transgene expression by induction of Treg cells
Language	English
Publishing date	2021-02-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2021.02.003
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Zs.A 7107: Show issues

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Article ; Online: Deep impact of the inactivation of the SecA2-only protein export pathway on the proteosurfaceome of Listeria monocytogenes.

Chafsey, Ingrid / Ostrowski, Rafal / Guilbaud, Morgan / Teixeira, Pilar / Herry, Jean-Marie / Caccia, Nelly / Chambon, Christophe / Hébraud, Michel / Azeredo, Joana / Bellon-Fontaine, Marie-Noëlle / Popowska, Magdalena / Desvaux, Mickaël

Journal of proteomics

2021 Volume 250, Page(s) 104388

Abstract: Listeria monocytogenes presents a dimorphism associated to the SecA2 activity with cells having a normal rod shape or a dysmorphic elongated filamentous form. Besides variation of the cell and colony morphotype, this cell differentiation has profound ... ...

Abstract	Listeria monocytogenes presents a dimorphism associated to the SecA2 activity with cells having a normal rod shape or a dysmorphic elongated filamentous form. Besides variation of the cell and colony morphotype, this cell differentiation has profound ecophysiological and physiopathological implications with collateral effects on virulence and pathogenicity, biotope colonisation, bacterial adhesion and biofilm formation. This suggests the SecA2-only protein export could influence the listerial cell surface, which was investigated first by characterising its properties in L. monocytogenes wt and ΔsecA2. The degree of hydrophilicity and Lewis acid-base properties appeared significantly affected upon SecA2 inactivation. As modification of electrostatic properties would owe to modification in the composition of cell-surface proteins, the proteosurfaceome was further investigated by shotgun label-free proteomic analysis with a comparative relative quantitative approach. Following secretomic analysis, the protein secretion routes of the identified proteins were mapped considering the cognate transport and post-translocational maturation systems, as well as protein categories and subcellular localisation. Differential protein abundance profiles coupled to network analysis revealed the SecA2 dependence of 48 proteins, including some related to cell envelope biogenesis, translation and protein export, which could account for modifications of adhesion and surface properties of L. monocytogenes upon SecA2 inactivation. This investigation unravelled the profound influence of SecA2 activity on the cell surface properties and proteosurfaceome of L. monocytogenes, which provides advanced insights about its ecophysiopathology. SIGNIFICANCE: L. monocytogenes is a foodborne zoonotic pathogen and etiological agent of human listeriosis. This species presents a cellular dimorphism associated to the SecA2 activity that has profound physiopathological and ecophysiological implications with collateral effects on bacterial virulence and colonisation. To explore the influence of the SecA2-only protein export on the listerial cell, the surface properties of L. monocytogenes expressing or depleted of SecA2 was characterised by microelectrophoresis, microbial affinity to solvents and contact angles analyses. As modifications of hydrophilicity and Lewis acid-base electrostatic properties would owe to modification in the composition of cell-surface proteins, the proteinaceous subset of the surfaceome, i.e. the proteosurfaceome, was investigated further by shotgun label-free proteomic analysis. This subproteome appeared quite impacted upon SecA2 inactivation with the identification of proteins accounting for modifications in the cell surface properties. The profound influence of SecA2 activity on the cell surface of L. monocytogenes was unravelled, which provides advanced insights about its ecophysiopathology.
MeSH term(s)	Adenosine Triphosphatases ; Bacterial Proteins/metabolism ; Humans ; Listeria monocytogenes/metabolism ; Membrane Transport Proteins/physiology ; Proteomics
Chemical Substances	Bacterial Proteins ; Membrane Transport Proteins ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2021-09-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2021.104388
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