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Article: Does IHU-Méditerranée Infection influence Gilead Sciences' stock price?

Chabrière, E

2020 Volume 39, Page(s) 100711

Abstract: During COVID-19 pandemic the Gilead Sciences stock prices rose sharply with large variations. These fluctuations have been tentatively related to communications, publications or leaks about remdesivir or hydroxychloroquine/azithromycin treatment. ...

Abstract	During COVID-19 pandemic the Gilead Sciences stock prices rose sharply with large variations. These fluctuations have been tentatively related to communications, publications or leaks about remdesivir or hydroxychloroquine/azithromycin treatment.
Keywords	covid19
Language	English
Publishing date	2020-09-30
Publishing country	England
Document type	Editorial
ZDB-ID	2750179-6
ISSN	2052-2975
ISSN	2052-2975
DOI	10.1016/j.nmni.2020.100711
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Article ; Online: AHL-Based Quorum Sensing Regulates the Biosynthesis of a Variety of Bioactive Molecules in Bacteria.

Gonzales, Mélanie / Jacquet, Pauline / Gaucher, Floriane / Chabrière, Éric / Plener, Laure / Daudé, David

Journal of natural products

2024 Volume 87, Issue 4, Page(s) 1268–1284

Abstract: Bacteria are social microorganisms that use communication systems known as quorum sensing (QS) to regulate diverse cellular behaviors including the production of various secreted molecules. Bacterial secondary metabolites are widely studied for their ... ...

Abstract	Bacteria are social microorganisms that use communication systems known as quorum sensing (QS) to regulate diverse cellular behaviors including the production of various secreted molecules. Bacterial secondary metabolites are widely studied for their bioactivities including antibiotic, antifungal, antiparasitic, and cytotoxic compounds. Besides playing a crucial role in natural bacterial niches and intermicrobial competition by targeting neighboring organisms and conferring survival advantages to the producer, these bioactive molecules may be of prime interest to develop new antimicrobials or anticancer therapies. This review focuses on bioactive compounds produced under acyl homoserine lactone-based QS regulation by Gram-negative bacteria that are pathogenic to humans and animals, including the
MeSH term(s)	Quorum Sensing/drug effects ; Acyl-Butyrolactones/metabolism ; Acyl-Butyrolactones/pharmacology ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry ; Gram-Negative Bacteria/drug effects ; Molecular Structure ; Humans ; Burkholderia/metabolism ; Chromobacterium/drug effects
Chemical Substances	Acyl-Butyrolactones ; Anti-Bacterial Agents
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	304325-3
ISSN	1520-6025 ; 0163-3864
ISSN (online)	1520-6025
ISSN	0163-3864
DOI	10.1021/acs.jnatprod.3c00672
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Article ; Online: Lactonase-mediated inhibition of quorum sensing largely alters phenotypes, proteome, and antimicrobial activities in

Gonzales, Mélanie / Plener, Laure / Armengaud, Jean / Armstrong, Nicholas / Chabrière, Éric / Daudé, David

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1190859

Abstract: Introduction: Burkholderia thailandensis: Methods: Using an enzyme-based quorum quenching (QQ) strategy, with the lactonase : Results: We demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic ... ...

Abstract	Introduction: Burkholderia thailandensis Methods: Using an enzyme-based quorum quenching (QQ) strategy, with the lactonase Results: We demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic activity, and antimicrobial molecule production. We further showed that QQ treatment drastically decreases Discussion: This study provides evidence that QS is of prime interest when it comes to understanding the virulence of
MeSH term(s)	Quorum Sensing/physiology ; Proteome/metabolism ; Proteomics ; Burkholderia/genetics ; Acyl-Butyrolactones/metabolism ; Phenotype
Chemical Substances	Proteome ; Acyl-Butyrolactones
Language	English
Publishing date	2023-06-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1190859
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Article ; Online: Applying molecular and phenotypic screening assays to identify efficient quorum quenching lactonases.

Billot, Raphaël / Plener, Laure / Grizard, Damien / Elias, Mikael H / Chabrière, Éric / Daudé, David

Enzyme and microbial technology

2022 Volume 160, Page(s) 110092

Abstract: ... Specifically, molecular screenings using six different AHL and based on two reporter strains; i.e ...

Abstract	Quorum sensing (QS) is a molecular communication system used by microorganisms to adopt behaviors in a cell density-dependent manner. Lactonase enzymes, able to hydrolyze the signal molecules acyl-homoserine lactones (AHL) can counteract QS-mediated virulence in Gram-negative bacteria. Optimizing lactonases activity or specificity for AHL through enzyme engineering approaches is thus highly attractive to increase protective effect. However, only a limited number of screening methods have been developed to handle and evaluate AHL-degrading enzyme libraries. Here, a series of screening procedures were developed to identify improved lactonases using two previously reported enzymes as benchmarks, namely SsoPox and GcL. Specifically, molecular screenings using six different AHL and based on two reporter strains; i.e., Chromobacterium violaceum CV026 and Pseudomonas putida KS35, are reported. In addition, three phenotype-based screenings aiming to evaluate the ability of enzymes to quench a particular QS-related behavior are reported, using C. violaceum, Pseudomonas aeruginosa and Vibrio harveyi as pathogenic type strains. These assays were used to screen a small-sized library and allowed for the identification of various improved variants. To confirm that these variants were real "hits", four of them were produced and purified. Their kinetic parameters against AHL substrates were found to be increased by 2-44.5 -fold as compared to the starting enzyme. Moreover, their increased activity was confirmed by measuring their ability to quench QS in different bacterial systems. These new assays will facilitate the screening of enzyme libraries and will pave the way for the development of proficient engineered QS-disrupting enzymes.
MeSH term(s)	Acyl-Butyrolactones/chemistry ; Acyl-Butyrolactones/metabolism ; Phenotype ; Pseudomonas aeruginosa/metabolism ; Quorum Sensing ; Virulence
Chemical Substances	Acyl-Butyrolactones
Language	English
Publishing date	2022-07-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	423729-8
ISSN	1879-0909 ; 0141-0229
ISSN (online)	1879-0909
ISSN	0141-0229
DOI	10.1016/j.enzmictec.2022.110092
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Article ; Online: Enzymatic decontamination of paraoxon-ethyl limits long-term effects in planarians.

Poirier, Laetitia / Plener, Laure / Daudé, David / Chabrière, Eric

Scientific reports

2020 Volume 10, Issue 1, Page(s) 3843

Abstract: Organophosphorus compounds (OP) are highly toxic molecules used as insecticides that inhibit cholinesterase enzymes involved in neuronal transmission. The intensive use of OP for vector control and agriculture has led to environmental pollutions ... ...

Abstract	Organophosphorus compounds (OP) are highly toxic molecules used as insecticides that inhibit cholinesterase enzymes involved in neuronal transmission. The intensive use of OP for vector control and agriculture has led to environmental pollutions responsible for severe intoxications and putative long-term effects on humans and wild animals. Many in vivo models were studied over the years to assess OP acute toxicity, but the long-term effects are poorly documented. Planarian, a freshwater flatworm having a cholinergic system, has emerged as a new original model for addressing both toxicity and developmental perturbations. We used Schmidtea mediterranea planarians to evaluate long-term effects of paraoxon-ethyl at two sublethal concentrations over three generations. Toxicity, developmental perturbations and disruption of behavior were rapidly observed and higher sensitivity to paraoxon-ethyl of next generations was noticed suggesting that low insecticide doses can induce transgenerational effects. With the view of limiting OP poisoning, SsoPox, an hyperthermostable enzyme issued from the archaea Saccharolobus solfataricus, was used to degrade paraoxon-ethyl prior to planarian exposure. The degradation products, although not lethal to the worms, were found to decrease cholinesterase activities for the last generation of planarians and to induce abnormalities albeit in lower proportion than insecticides.
MeSH term(s)	Animals ; Biodegradation, Environmental ; Cholinesterases/genetics ; Evolution, Molecular ; Gene Expression Regulation, Enzymologic/drug effects ; Paraoxon/analogs & derivatives ; Paraoxon/metabolism ; Planarians/drug effects ; Planarians/enzymology ; Planarians/genetics ; Planarians/metabolism ; Time Factors
Chemical Substances	ethylparaoxon ; Cholinesterases (EC 3.1.1.8) ; Paraoxon (Q9CX8P80JW)
Language	English
Publishing date	2020-03-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-60846-1
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Article ; Online: Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms.

Diene, Seydina M / Pontarotti, Pierre / Azza, Saïd / Armstrong, Nicholas / Pinault, Lucile / Chabrière, Eric / Colson, Philippe / Rolain, Jean-Marc / Raoult, Didier

Cells

2023 Volume 12, Issue 13

Abstract: ... by conserved motifs (i.e., HxHxDH) and are not only limited to bacteria. Indeed, as the result ...

Abstract	β-lactamase enzymes have generated significant interest due to their ability to confer resistance to the most commonly used family of antibiotics in human medicine. Among these enzymes, the class B β-lactamases are members of a superfamily of metallo-β-lactamase (MβL) fold proteins which are characterised by conserved motifs (i.e., HxHxDH) and are not only limited to bacteria. Indeed, as the result of several barriers, including low sequence similarity, default protein annotation, or untested enzymatic activity, MβL fold proteins have long been unexplored in other organisms. However, thanks to search approaches which are more sensitive compared to classical Blast analysis, such as the use of common ancestors to identify distant homologous sequences, we are now able to highlight their presence in different organisms including Bacteria, Archaea, Nanoarchaeota, Asgard, Humans, Giant viruses, and Candidate Phyla Radiation (CPR). These MβL fold proteins are multifunctional enzymes with diverse enzymatic or non-enzymatic activities of which, at least thirteen activities have been reported such as β-lactamase, ribonuclease, nuclease, glyoxalase, lactonase, phytase, ascorbic acid degradation, anti-cancer drug degradation, or membrane transport. In this review, we (i) discuss the existence of MβL fold enzymes in the different domains of life, (ii) present more suitable approaches to better investigating their homologous sequences in unsuspected sources, and (iii) report described MβL fold enzymes with demonstrated enzymatic or non-enzymatic activities.
MeSH term(s)	Humans ; beta-Lactamases/metabolism ; Bacteria/metabolism ; Anti-Bacterial Agents
Chemical Substances	beta-Lactamases (EC 3.5.2.6) ; Anti-Bacterial Agents
Language	English
Publishing date	2023-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12131752
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Article ; Online: AmyP53, a Therapeutic Peptide Candidate for the Treatment of Alzheimer's and Parkinson's Disease: Safety, Stability, Pharmacokinetics Parameters and Nose-to Brain Delivery.

Di Scala, Coralie / Armstrong, Nicholas / Chahinian, Henri / Chabrière, Eric / Fantini, Jacques / Yahi, Nouara

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Neurodegenerative disorders are a major public health issue. Despite decades of research efforts, we are still seeking an efficient cure for these pathologies. The initial paradigm of large aggregates of amyloid proteins (amyloid plaques, Lewis bodies) ... ...

Abstract	Neurodegenerative disorders are a major public health issue. Despite decades of research efforts, we are still seeking an efficient cure for these pathologies. The initial paradigm of large aggregates of amyloid proteins (amyloid plaques, Lewis bodies) as the root cause of Alzheimer's and Parkinson's diseases has been mostly dismissed. Instead, membrane-bound oligomers forming Ca
MeSH term(s)	Animals ; Humans ; Rats ; Parkinson Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/metabolism ; Rats, Inbred Lew ; alpha-Synuclein/metabolism ; Amyloid/metabolism ; Brain/metabolism ; Amyloidogenic Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; alpha-Synuclein ; Amyloid ; Amyloidogenic Proteins
Language	English
Publishing date	2022-11-02
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/ijms232113383
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Article: Intoxication aux organophosphorés : vers des traitements enzymatiques.

Jacquet, P / Poirier, L / Daudé, D / Chabrière, E

Annales pharmaceutiques francaises

2019 Volume 77, Issue 5, Page(s) 349–362

Abstract: Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for ... ...

Title translation	Organophosphorus poisoning: Towards enzymatic treatments.
Abstract	Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for many poisonings worldwide. OP toxicity may result either from acute or chronic exposure, and their poisoning effect were evaluated using several animal models. These latter were also used for evaluating the efficacy of antidotes. Strategies based on enzymes that can trap (stoichiometric bioscavengers) or degrade (catalytic bioscavengers) OP, were particularly studied since they allow effective decontamination, without toxicity or environmental impact. This review summarizes the results obtained in vivo with enzymes through three levels: prophylaxis, treatment and external decontamination. The efficiency of enzymatic treatments in different animal models is presented and the relevance of these models is also discussed for a better extrapolation to humans.
MeSH term(s)	Animals ; Antidotes/therapeutic use ; Chemical Warfare Agents ; Cholinesterase Reactivators/therapeutic use ; Enzyme Replacement Therapy/methods ; Humans ; Insecticides/poisoning ; Organophosphate Poisoning/enzymology ; Organophosphate Poisoning/therapy
Chemical Substances	Antidotes ; Chemical Warfare Agents ; Cholinesterase Reactivators ; Insecticides
Language	French
Publishing date	2019-06-26
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	307-4
ISSN	0003-4509
ISSN	0003-4509
DOI	10.1016/j.pharma.2019.06.002
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Article: Changes in Active Site Loop Conformation Relate to the Transition toward a Novel Enzymatic Activity.

Jacquet, Pauline / Billot, Raphaël / Shimon, Amir / Hoekstra, Nathan / Bergonzi, Céline / Jenks, Anthony / Chabrière, Eric / Daudé, David / Elias, Mikael H

bioRxiv : the preprint server for biology

2023

Abstract: Enzymatic promiscuity, the ability of enzymes to catalyze multiple, distinct chemical reactions, has been well documented and is hypothesized to be a major driver for the emergence of new enzymatic functions. Yet, the molecular mechanisms involved in the ...

Abstract	Enzymatic promiscuity, the ability of enzymes to catalyze multiple, distinct chemical reactions, has been well documented and is hypothesized to be a major driver for the emergence of new enzymatic functions. Yet, the molecular mechanisms involved in the transition from one activity to another remain debated and elusive. Here, we evaluated the redesign of the active site binding cleft of the lactonase
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.22.541809
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Article ; Online: Modèles alternatifs (6) - La planaire, un modèle animal original pour la toxicologie.

Poirier, Laetitia / Ghigo, Éric / Daudé, David / Chabrière, Éric

Medecine sciences : M/S

2019 Volume 35, Issue 6-7, Page(s) 544–548

Abstract: Since a few decades, a new invertebrate animal model has emerged in toxicology studies: the planarian. This non-parasitic flatworm, from phylum Platyhelminthes, has an amazing regenerative capacity and has been described as "immortal under the edge of ... ...

Title translation	Planarian, an emerging animal model for toxicology studies.
Abstract	Since a few decades, a new invertebrate animal model has emerged in toxicology studies: the planarian. This non-parasitic flatworm, from phylum Platyhelminthes, has an amazing regenerative capacity and has been described as "immortal under the edge of the knife" in 1814 by Dalyell. This formidable capacity is due to the abundance of stem cells called neoblasts, allowing for a tiny fragment equivalent to 1/279
MeSH term(s)	Animals ; Disease Models, Animal ; Insecticides/toxicity ; Metals/toxicity ; Models, Animal ; Neurotoxicity Syndromes/pathology ; Organometallic Compounds/toxicity ; Planarians/physiology ; Toxicity Tests/methods ; Toxicity Tests/trends ; Toxicology/methods ; Toxicology/trends
Chemical Substances	Insecticides ; Metals ; Organometallic Compounds
Language	French
Publishing date	2019-07-05
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2019110
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