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Article ; Online: Evaluating cognitive aids in hospital management of severe trauma patients: a prospective randomised high-fidelity simulation trial.

Fleury, Maxime J J / Nicolleau, Claire / Bouhours, Guillaume / Conté, Mathieu / Martin, Ludovic / Lasocki, Sigismond / Léger, Maxime

British journal of anaesthesia

2023 Volume 131, Issue 5, Page(s) e150–e152

MeSH term(s)	Humans ; Prospective Studies ; High Fidelity Simulation Training ; Simulation Training ; Cognition ; Hospitals
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Randomized Controlled Trial ; Letter
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2023.08.028
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Article ; Online: Varying susceptibility of clinical and environmental Scedosporium isolates to chemical oxidative stress in conidial germination.

Staerck, Cindy / Godon, Charlotte / Bouchara, Jean-Philippe / Fleury, Maxime J J

Archives of microbiology

2018 Volume 200, Issue 3, Page(s) 517–523

Abstract: Scedosporium species are opportunistic pathogens causing a great variety of infections in both immunocompetent and immunocompromised individuals. The Scedosporium genus ranks the second among the filamentous fungi colonizing the airways of patients with ... ...

Abstract	Scedosporium species are opportunistic pathogens causing a great variety of infections in both immunocompetent and immunocompromised individuals. The Scedosporium genus ranks the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus, and most species are capable to chronically colonize the respiratory tract of these patients. Nevertheless, few data are available regarding evasion of the inhaled conidia to the host immune response. Upon microbial infection, macrophages and neutrophils release reactive oxygen species (ROS). To colonize the respiratory tract, the conidia need to germinate despite the oxidative stress generated by phagocytic cells. Germination of spores from different clinical or environmental isolates of the major Scedosporium species was investigated in oxidative stress conditions. All tested species showed susceptibility to oxidative stress. However, when comparing clinical and environmental isolates, differences in germination capabilities under oxidative stress conditions were seen between species as well as within each species. Among environmental isolates, Scedosporium aurantiacum isolates were the most resistant to oxidative stress whereas Scedosporium dehoogii were the most susceptible. Overall, the differences observed between Scedosporium species in the capacity to germinate under oxidative stress conditions could explain their varying prevalence and pathogenicity.
MeSH term(s)	Cystic Fibrosis/microbiology ; Humans ; Oxidants/pharmacology ; Oxidative Stress ; Paraquat/pharmacology ; Reactive Oxygen Species ; Scedosporium/drug effects ; Scedosporium/growth & development ; Scedosporium/isolation & purification ; Spores, Fungal/drug effects ; Spores, Fungal/growth & development ; Spores, Fungal/isolation & purification ; Vitamin K 3/pharmacology
Chemical Substances	Oxidants ; Reactive Oxygen Species ; Vitamin K 3 (723JX6CXY5) ; Paraquat (PLG39H7695)
Language	English
Publishing date	2018-02-20
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124824-8
ISSN	1432-072X ; 0302-8933
ISSN (online)	1432-072X
ISSN	0302-8933
DOI	10.1007/s00203-018-1491-5
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Article ; Online: Transcriptional profiling of Scedosporium apiospermum enzymatic antioxidant gene battery unravels the involvement of thioredoxin reductases against chemical and phagocytic cells oxidative stress.

Staerck, Cindy / Tabiasco, Julie / Godon, Charlotte / Delneste, Yves / Bouchara, Jean-Philippe / Fleury, Maxime J J

Medical mycology

2018 Volume 57, Issue 3, Page(s) 363–373

Abstract: Scedosporium species rank the second, after Aspergillus fumigatus, among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Development of microorganisms in the respiratory tract depends on their capacity to evade killing ...

Abstract	Scedosporium species rank the second, after Aspergillus fumigatus, among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Development of microorganisms in the respiratory tract depends on their capacity to evade killing by the host immune system, particularly through the oxidative response of macrophages and neutrophils, with the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS). This is particularly true in the airways of CF patients which display an exacerbated inflammatory reaction. To protect themselves, pathogens have developed various enzymatic antioxidant systems implicated in ROS degradation, including superoxide dismutases, catalases, cytochrome C peroxidases, chloroperoxidases and enzymes of the glutathione and thioredoxin systems, or in RNS degradation, that is, flavohemoglobins, nitrate reductases, and nitrite reductases. Here we investigated the transcriptional regulation of the enzymatic antioxidant gene battery in 24-h-old hyphae of Scedosporium apiospermum in response to oxidative stress induced chemically or by exposure to activated phagocytic cells. We showed that 21 out of the 33 genes potentially implicated in the oxidative or nitrosative stress response were overexpressed upon exposure of the fungus to various chemical oxidants, while they were only 13 in co-cultures with macrophages or neutrophils. Among them, genes encoding two thioredoxin reductases and to a lesser extent, a peroxiredoxin and one catalase were found to be overexpressed after chemical oxidative stress as well as in co-cultures. These results suggest that thioredoxin reductases, which are known to be virulence factors in other pathogenic fungi, play a key role in pathogenesis of scedosporiosis, and may be new drug targets.
MeSH term(s)	Antioxidants/metabolism ; Catalase/genetics ; Gene Expression Profiling ; Hyphae/genetics ; Oxidation-Reduction ; Oxidative Stress ; Phagocytes/microbiology ; Phagocytes/pathology ; Reactive Oxygen Species/metabolism ; Scedosporium/enzymology ; Scedosporium/genetics ; Scedosporium/pathogenicity ; Thioredoxin-Disulfide Reductase/genetics ; Thioredoxin-Disulfide Reductase/metabolism
Chemical Substances	Antioxidants ; Reactive Oxygen Species ; Catalase (EC 1.11.1.6) ; Thioredoxin-Disulfide Reductase (EC 1.8.1.9)
Language	English
Publishing date	2018-06-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1421796-x
ISSN	1460-2709 ; 1369-3786
ISSN (online)	1460-2709
ISSN	1369-3786
DOI	10.1093/mmy/myy033
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Article ; Online: Human papillomavirus type 16 pseudovirions with few point mutations in L1 major capsid protein FG loop could escape actual or future vaccination for potential use in gene therapy.

Fleury, Maxime J J / Touzé, Antoine / Coursaget, Pierre

Molecular biotechnology

2014 Volume 56, Issue 5, Page(s) 479–486

Abstract: HPV prophylactic vaccination based on VLPs was implemented 7 years ago and has now shown a high degree of efficiency to reduce HPV-induced lesions. Moreover, it was shown that HPV-derived virus-like particles or pseudovirions could be used as gene ... ...

Abstract	HPV prophylactic vaccination based on VLPs was implemented 7 years ago and has now shown a high degree of efficiency to reduce HPV-induced lesions. Moreover, it was shown that HPV-derived virus-like particles or pseudovirions could be used as gene therapy vectors. As a consequence, characterization of the antigenic structure of HPV capsids is crucial for designing future HPV vaccines with better or broader efficacy and for the design of HPV-derived gene therapy vectors with reduced immunogenicity or vaccination escaping. In this study, we have generated 10 HPV16 FG loop L1 protein mutants and analyzed their ability to self-assemble into VLP, their immunogenicity, and their ability to transduce cells when used as pseudovirions. Most of the mutants had lost their ability to transduce cells at the exception of two chimeric HPV16/31 L1 protein FG loop mutants. Sera from mice immunized with HPV16 L1 wt VLPs very weakly neutralized pseudovirions derived from these two HPV16/31 L1 protein FG loop mutants. These findings suggest that only a few point substitutions within the FG loop are sufficient to generate a new serotype escaping vaccination. As a consequence, derived pseudovirions might be suitable as gene therapy vectors in vaccinated subjects.
MeSH term(s)	Animals ; Capsid Proteins/genetics ; Capsid Proteins/immunology ; Capsid Proteins/metabolism ; Genetic Therapy ; Human papillomavirus 16/genetics ; Human papillomavirus 16/immunology ; Human papillomavirus 16/metabolism ; Humans ; Mice ; Oncogene Proteins, Viral/genetics ; Oncogene Proteins, Viral/immunology ; Oncogene Proteins, Viral/metabolism ; Point Mutation/genetics ; Viral Vaccines/immunology ; Virion/genetics ; Virion/immunology ; Virion/metabolism
Chemical Substances	Capsid Proteins ; Oncogene Proteins, Viral ; Viral Vaccines
Language	English
Publishing date	2014-03-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1193057-3
ISSN	1559-0305 ; 1073-6085
ISSN (online)	1559-0305
ISSN	1073-6085
DOI	10.1007/s12033-014-9745-1
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Article: Human Papillomavirus Type 16 Pseudovirions with Few Point Mutations in L1 Major Capsid Protein FG Loop Could Escape Actual or Future Vaccination for Potential Use in Gene Therapy

Fleury, Maxime J. J / Touzé, Antoine / Coursaget, Pierre

Molecular biotechnology. 2014 May, v. 56, no. 5

2014

Abstract	HPV prophylactic vaccination based on VLPs was implemented 7 years ago and has now shown a high degree of efficiency to reduce HPV-induced lesions. Moreover, it was shown that HPV-derived virus-like particles or pseudovirions could be used as gene therapy vectors. As a consequence, characterization of the antigenic structure of HPV capsids is crucial for designing future HPV vaccines with better or broader efficacy and for the design of HPV-derived gene therapy vectors with reduced immunogenicity or vaccination escaping. In this study, we have generated 10 HPV16 FG loop L1 protein mutants and analyzed their ability to self-assemble into VLP, their immunogenicity, and their ability to transduce cells when used as pseudovirions. Most of the mutants had lost their ability to transduce cells at the exception of two chimeric HPV16/31 L1 protein FG loop mutants. Sera from mice immunized with HPV16 L1 wt VLPs very weakly neutralized pseudovirions derived from these two HPV16/31 L1 protein FG loop mutants. These findings suggest that only a few point substitutions within the FG loop are sufficient to generate a new serotype escaping vaccination. As a consequence, derived pseudovirions might be suitable as gene therapy vectors in vaccinated subjects.
Keywords	Human papillomavirus 16 ; capsid ; coat proteins ; gene therapy ; immune response ; mice ; mutants ; neutralization ; point mutation ; serotypes ; vaccination ; vaccines ; virus-like particles
Language	English
Dates of publication	2014-05
Size	p. 479-486.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	1193057-3
ISSN	1559-0305 ; 1073-6085
ISSN (online)	1559-0305
ISSN	1073-6085
DOI	10.1007/s12033-014-9745-1
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Article ; Online: Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype.

Bissett, Sara L / Godi, Anna / Fleury, Maxime J J / Touze, Antoine / Cocuzza, Clementina / Beddows, Simon

Journal of virology

2015 Volume 89, Issue 15, Page(s) 7748–7757

Abstract: Unlabelled: We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) ... ...

Abstract	Unlabelled: We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity. Importance: The virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype.
MeSH term(s)	Adolescent ; Alphapapillomavirus/classification ; Alphapapillomavirus/genetics ; Alphapapillomavirus/immunology ; Alphapapillomavirus/isolation & purification ; Amino Acid Sequence ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Capsid Proteins/chemistry ; Capsid Proteins/genetics ; Capsid Proteins/immunology ; Child ; Female ; Genetic Variation ; Humans ; Molecular Sequence Data ; Neutralization Tests ; Papillomavirus Infections/immunology ; Papillomavirus Infections/virology ; Phylogeny ; Sequence Alignment
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Capsid Proteins
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00842-15
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Article ; Online: The secreted polyketide boydone A is responsible for the anti-Staphylococcus aureus activity of Scedosporium boydii.

Staerck, Cindy / Landreau, Anne / Herbette, Gaëtan / Roullier, Catherine / Bertrand, Samuel / Siegler, Benjamin / Larcher, Gérald / Bouchara, Jean-Philippe / Fleury, Maxime J J

FEMS microbiology letters

2017 Volume 364, Issue 22

Abstract: Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). ...

Abstract	Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity that may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high-performance liquid chromatography and high-resolution electrospray ionization-mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together, these results suggest that this six-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis.
Language	English
Publishing date	2017-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1093/femsle/fnx223
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Article ; Online: Scedosporium boydii CatA1 and SODC recombinant proteins, new tools for serodiagnosis of Scedosporium infection of patients with cystic fibrosis.

Mina, Sara / Staerck, Cindy / Marot, Agnès / Godon, Charlotte / Calenda, Alphonse / Bouchara, Jean-Philippe / Fleury, Maxime J J

Diagnostic microbiology and infectious disease

2017 Volume 89, Issue 4, Page(s) 282–287

Abstract: Scedosporium species rank the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus. In CF, these fungi may cause various respiratory infections similar to those caused by A. ... ...

Abstract	Scedosporium species rank the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus. In CF, these fungi may cause various respiratory infections similar to those caused by A. fumigatus, including bronchitis and allergic broncho-pulmonary mycoses. Diagnosis of these infections relies on the detection of serum antibodies using crude antigenic extracts. However, many components of these extracts are common to Scedosporium and Aspergillus species, leading to cross-reactions. Here, 5 recombinant proteins from S. apiospermum or S. boydii were produced, and their value in serodiagnosis of Scedosporium infections was investigated by enzyme-linked immunosorbent assay. Two of them, corresponding to the Scedosporium catalase A1 or cytosolic Cu,Zn-superoxyde dismutase, allowed the detection of Scedosporium infection, and the differentiation with an Aspergillus infection. These recombinant proteins therefore may serve as a basis for the development of a standardized serological test.
MeSH term(s)	Antibodies, Fungal/blood ; Antigens, Fungal/blood ; Aspergillus fumigatus/isolation & purification ; Catalase/analysis ; Cystic Fibrosis/microbiology ; Fungal Proteins/analysis ; Humans ; Mycoses/diagnosis ; Pichia ; Reactive Oxygen Species/metabolism ; Recombinant Proteins/analysis ; Scedosporium/enzymology ; Serologic Tests ; Superoxide Dismutase-1/analysis
Chemical Substances	Antibodies, Fungal ; Antigens, Fungal ; Fungal Proteins ; Reactive Oxygen Species ; Recombinant Proteins ; Catalase (EC 1.11.1.6) ; Superoxide Dismutase-1 (EC 1.15.1.1)
Language	English
Publishing date	2017-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	604920-5
ISSN	1879-0070 ; 0732-8893
ISSN (online)	1879-0070
ISSN	0732-8893
DOI	10.1016/j.diagmicrobio.2017.08.013
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Article ; Online: Microbial antioxidant defense enzymes.

Staerck, Cindy / Gastebois, Amandine / Vandeputte, Patrick / Calenda, Alphonse / Larcher, Gérald / Gillmann, Louiza / Papon, Nicolas / Bouchara, Jean-Philippe / Fleury, Maxime J J

Microbial pathogenesis

2017 Volume 110, Page(s) 56–65

Abstract: Free radicals are often described as chemical compounds characterized by unpaired electrons in their outer orbital rendering them highly reactive species. In mammalians, studies on free radicals were focused on reactive oxygen species (ROS) or reactive ... ...

Abstract	Free radicals are often described as chemical compounds characterized by unpaired electrons in their outer orbital rendering them highly reactive species. In mammalians, studies on free radicals were focused on reactive oxygen species (ROS) or reactive nitrogen species (RNS) due to their relative importance in physiological as well as in pathological processes. These cellular compounds are produced by different physiological systems such as the aerobic metabolism and play a major role in cell signaling pathways but also in the host immune defenses against pathogenic microorganisms. ROS and RNS are highly reactive species with potentially harmful effects on any cellular components (lipids, proteins and nucleic acids) when produced with a high level. To maintain ROS and RNS at a non-toxic concentration, enzymatic and non-enzymatic cellular antioxidants coordinate the balance between their production and their degradation. Superoxide dismutases, catalases, glutathione system, thioredoxin system, peroxidase systems, flavohemoglobins and nitrate or nitrite reductases represent the prominent enzymatic antioxidants used to scavenge excess of internal as well as external ROS and RNS. Bacteria, fungi and parasites also display similar enzymatic activities to escape the host oxidative defenses during the immune response against infectious processes. Here we summarize current knowledge on the enzymatic systems that allow microorganisms to fight against ROS and RNS, and shed light on the role that take some of them in microbial infections. Such microbial protective systems are considered as virulence factors, and therefore represent key targets for diagnosis of the infections or development of anti-infectious drugs.
Language	English
Publishing date	2017-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2017.06.015
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Article ; Online: Purification and characterization of a mycelial catalase from Scedosporium boydii, a useful tool for specific antibody detection in patients with cystic fibrosis.

Mina, Sara / Marot-Leblond, Agnès / Cimon, Bernard / Fleury, Maxime J J / Larcher, Gérald / Bouchara, Jean-Philippe / Robert, Raymond

Clinical and vaccine immunology : CVI

2014 Volume 22, Issue 1, Page(s) 37–45

Abstract: Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a wide variety of infections in immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex, which usually ... ...

Abstract	Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a wide variety of infections in immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex, which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF) and may lead to allergic bronchopulmonary mycoses, sensitization, or respiratory infections. Upon microbial infection, host phagocytic cells release reactive oxygen species (ROS), such as hydrogen peroxide, as part of the antimicrobial response. Catalases are known to protect pathogens against ROS by detoxification of the hydrogen peroxide. Here, we investigated the catalase equipment of Scedosporium boydii, one of the major pathogenic species in the S. apiospermum species complex. Three catalases were identified, and the mycelial catalase A1 was purified to homogeneity by a three-step chromatographic process. This enzyme is a monofunctional tetrameric protein of 460 kDa, consisting of four 82-kDa glycosylated subunits. The potential usefulness of this enzyme in serodiagnosis of S. apiospermum infections was then investigated by an enzyme-linked immunosorbent assay (ELISA), using 64 serum samples from CF patients. Whatever the species involved in the S. apiospermum complex, sera from infected patients were clearly differentiated from sera from patients with an Aspergillus fumigatus infection or those from CF patients without clinical and biological signs of a fungal infection and without any fungus recovered from sputum samples. These results suggest that catalase A1 is a good candidate for the development of an immunoassay for serodiagnosis of infections caused by the S. apiospermum complex in patients with CF.
MeSH term(s)	Antibodies, Fungal/blood ; Antigens, Fungal/chemistry ; Antigens, Fungal/isolation & purification ; Catalase/chemistry ; Catalase/isolation & purification ; Chromatography, Liquid/methods ; Cystic Fibrosis/complications ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Molecular Weight ; Mycelium/enzymology ; Mycoses/diagnosis ; Protein Multimerization ; Scedosporium/enzymology ; Serologic Tests/methods
Chemical Substances	Antibodies, Fungal ; Antigens, Fungal ; Catalase (EC 1.11.1.6)
Language	English
Publishing date	2014-10-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2221082-9
ISSN	1556-679X ; 1556-6811
ISSN (online)	1556-679X
ISSN	1556-6811
DOI	10.1128/CVI.00482-14
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