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  1. Article ; Online: Cell death in Leishmania.

    Basmaciyan, Louise / Casanova, Magali

    Parasite (Paris, France)

    2019  Volume 26, Page(s) 71

    Abstract: Leishmaniases still represent a global scourge and new therapeutic tools are necessary to replace the current expensive, difficult to administer treatments that induce numerous adverse effects and for which resistance is increasingly worrying. In this ... ...

    Title translation La mort cellulaire chez Leishmania.
    Abstract Leishmaniases still represent a global scourge and new therapeutic tools are necessary to replace the current expensive, difficult to administer treatments that induce numerous adverse effects and for which resistance is increasingly worrying. In this context, the particularly original organization of the Leishmania parasite in comparison to higher eukaryotes is a great advantage. It allows for the development of new, very specific, and thus non-cytotoxic treatments. Among these originalities, Leishmania cell death can be cited. Despite a classic pattern of apoptosis, key mammalian apoptotic proteins are not present in Leishmania, such as caspases, cell death receptors, and anti-apoptotic molecules. Recent studies have helped to develop a better understanding of parasite cell death, identifying new proteins or even new apoptotic pathways. This review provides an overview of the current knowledge on Leishmania cell death, describing its physiological roles and its phenotype, and discusses the involvement of various proteins: endonuclease G, metacaspase, aquaporin Li-BH3AQP, calpains, cysteine proteinase C, LmjHYD36 and Lmj.22.0600. From these data, potential apoptotic pathways are suggested. This review also offers tools to identify new Leishmania cell death effectors. Lastly, different approaches to use this knowledge for the development of new therapeutic tools are suggested: either inhibition of Leishmania cell death or activation of cell death for instance by treating cells with proteins or peptides involved in parasite death fused to a cell permeant peptide or encapsulated into a lipidic vector to target intra-macrophagic Leishmania cells.
    MeSH term(s) Animals ; Apoptosis ; Cell Death ; Humans ; Leishmania/drug effects ; Leishmania/enzymology ; Leishmania/physiology ; Leishmaniasis/drug therapy ; Metabolic Networks and Pathways/drug effects ; Phenotype ; Psychodidae/parasitology
    Language English
    Publishing date 2019-12-11
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 1187629-3
    ISSN 1776-1042 ; 1252-607X
    ISSN (online) 1776-1042
    ISSN 1252-607X
    DOI 10.1051/parasite/2019071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A potential acetyltransferase involved in Leishmania major metacaspase-dependent cell death.

    Basmaciyan, Louise / Azas, Nadine / Casanova, Magali

    Parasites & vectors

    2019  Volume 12, Issue 1, Page(s) 266

    Abstract: Background: Currently, there is no satisfactory treatment for leishmaniases, owing to the cost, mode of administration, side effects and to the increasing emergence of drug resistance. As a consequence, the proteins involved in Leishmania apoptosis seem ...

    Abstract Background: Currently, there is no satisfactory treatment for leishmaniases, owing to the cost, mode of administration, side effects and to the increasing emergence of drug resistance. As a consequence, the proteins involved in Leishmania apoptosis seem a target of choice for the development of new therapeutic tools against these neglected tropical diseases. Indeed, Leishmania cell death, while phenotypically similar to mammalian apoptosis, is very peculiar, involving no homologue of the key mammalian apoptotic proteins such as caspases and death receptors. Furthermore, very few proteins involved in Leishmania apoptosis have been identified.
    Results: We identified a protein involved in Leishmania apoptosis from a library of genes overexpressed during Leishmania differentiation during which autophagy occurs. Indeed, the gene was overexpressed when L. major cell death was induced by curcumin or miltefosine. Furthermore, its overexpression increased L. major curcumin- and miltefosine-induced apoptosis. This gene, named LmjF.22.0600, whose expression is dependent on the expression of the metacaspase, another apoptotic protein, encodes a putative acetyltransferase.
    Conclusions: This new protein, identified as being involved in Leishmania apoptosis, will contribute to a better understanding of Leishmania death, which is needed owing to the absence of a satisfactory treatment against leishmaniases. It will also allow a better understanding of the original apoptotic pathways of eukaryotes in general, while evidence of the existence of such pathways is accumulating.
    MeSH term(s) Acetyltransferases/genetics ; Acetyltransferases/isolation & purification ; Apoptosis ; Caspases/genetics ; Curcumin/pharmacology ; Leishmania major/drug effects ; Leishmania major/enzymology ; Leishmaniasis/drug therapy ; Phosphorylcholine/analogs & derivatives ; Phosphorylcholine/pharmacology ; Protozoan Proteins/genetics ; Protozoan Proteins/isolation & purification
    Chemical Substances Protozoan Proteins ; Phosphorylcholine (107-73-3) ; miltefosine (53EY29W7EC) ; Acetyltransferases (EC 2.3.1.-) ; Caspases (EC 3.4.22.-) ; Curcumin (IT942ZTH98)
    Language English
    Publishing date 2019-05-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2409480-8
    ISSN 1756-3305 ; 1756-3305
    ISSN (online) 1756-3305
    ISSN 1756-3305
    DOI 10.1186/s13071-019-3526-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A novel hydrolase with a pro-death activity from the protozoan parasite

    Basmaciyan, Louise / Jacquet, Pauline / Azas, Nadine / Casanova, Magali

    Cell death discovery

    2019  Volume 5, Page(s) 99

    Abstract: Apoptosis is a cell death process generally described as involving a cascade of caspase activation, death receptors and/or pro- and antiapoptotic molecules from the BcL-2 family. But about 20 years ago, a caspase-independent apoptotic pathway has been ... ...

    Abstract Apoptosis is a cell death process generally described as involving a cascade of caspase activation, death receptors and/or pro- and antiapoptotic molecules from the BcL-2 family. But about 20 years ago, a caspase-independent apoptotic pathway has been described. Regarding this pathway, we can learn a lot from
    Language English
    Publishing date 2019-05-24
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-019-0178-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus.

    Casanova, Magali / Maresca, Marc / Poncin, Isabelle / Point, Vanessa / Olleik, Hamza / Boidin-Wichlacz, Céline / Tasiemski, Aurélie / Mabrouk, Kamel / Cavalier, Jean-François / Canaan, Stéphane

    Journal of biomedical science

    2024  Volume 31, Issue 1, Page(s) 18

    Abstract: Background: Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its ... ...

    Abstract Background: Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective. In this context, antimicrobial peptides (AMPs) active against bacterial strains and less prompt to cause resistance, represent a good alternative to conventional antibiotics. Herein, we evaluated the effect of three arenicin isoforms, possessing two or four Cysteines involved in one (Ar-1, Ar-2) or two disulfide bonds (Ar-3), on the in vitro growth of M. abscessus.
    Methods: The respective disulfide-free AMPs, were built by replacing the Cysteines with alpha-amino-n-butyric acid (Abu) residue. We evaluated the efficiency of the eight arenicin derivatives through their antimicrobial activity against M. abscessus strains, their cytotoxicity towards human cell lines, and their hemolytic activity on human erythrocytes. The mechanism of action of the Ar-1 peptide was further investigated through membrane permeabilization assay, electron microscopy, lipid insertion assay via surface pressure measurement, and the induction of resistance assay.
    Results: Our results demonstrated that Ar-1 was the safest peptide with no toxicity towards human cells and no hemolytic activity, and the most active against M. abscessus growth. Ar-1 acts by insertion into mycobacterial lipids, resulting in a rapid membranolytic effect that kills M. abscessus without induction of resistance.
    Conclusion: Overall, the present study emphasized Ar-1 as a potential new alternative to conventional antibiotics in the treatment of CF-associated bacterial infection related to M. abscessus.
    MeSH term(s) Humans ; Mycobacterium abscessus ; Mycobacterium Infections, Nontuberculous/drug therapy ; Anti-Bacterial Agents/pharmacology ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/microbiology ; Peptides/pharmacology ; Microbial Sensitivity Tests ; Polystyrenes
    Chemical Substances Amberlite XAD-2 resin (9060-05-3) ; Anti-Bacterial Agents ; Peptides ; Polystyrenes
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1193378-1
    ISSN 1423-0127 ; 1021-7770
    ISSN (online) 1423-0127
    ISSN 1021-7770
    DOI 10.1186/s12929-024-01007-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: A potential acetyltransferase involved in Leishmania major metacaspase-dependent cell death

    Basmaciyan, Louise / Azas, Nadine / Casanova, Magali

    Parasites & vectors. 2019 Dec., v. 12, no. 1

    2019  

    Abstract: BACKGROUND: Currently, there is no satisfactory treatment for leishmaniases, owing to the cost, mode of administration, side effects and to the increasing emergence of drug resistance. As a consequence, the proteins involved in Leishmania apoptosis seem ... ...

    Abstract BACKGROUND: Currently, there is no satisfactory treatment for leishmaniases, owing to the cost, mode of administration, side effects and to the increasing emergence of drug resistance. As a consequence, the proteins involved in Leishmania apoptosis seem a target of choice for the development of new therapeutic tools against these neglected tropical diseases. Indeed, Leishmania cell death, while phenotypically similar to mammalian apoptosis, is very peculiar, involving no homologue of the key mammalian apoptotic proteins such as caspases and death receptors. Furthermore, very few proteins involved in Leishmania apoptosis have been identified. RESULTS: We identified a protein involved in Leishmania apoptosis from a library of genes overexpressed during Leishmania differentiation during which autophagy occurs. Indeed, the gene was overexpressed when L. major cell death was induced by curcumin or miltefosine. Furthermore, its overexpression increased L. major curcumin- and miltefosine-induced apoptosis. This gene, named LmjF.22.0600, whose expression is dependent on the expression of the metacaspase, another apoptotic protein, encodes a putative acetyltransferase. CONCLUSIONS: This new protein, identified as being involved in Leishmania apoptosis, will contribute to a better understanding of Leishmania death, which is needed owing to the absence of a satisfactory treatment against leishmaniases. It will also allow a better understanding of the original apoptotic pathways of eukaryotes in general, while evidence of the existence of such pathways is accumulating.
    Keywords Leishmania major ; acetyltransferases ; adverse effects ; apoptosis ; autophagy ; caspases ; curcumin ; death ; death domain receptors ; drug resistance ; eukaryotic cells ; gene overexpression ; genes ; leishmaniasis ; mammals ; therapeutics ; tropical diseases
    Language English
    Dates of publication 2019-12
    Size p. 266.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2409480-8
    ISSN 1756-3305
    ISSN 1756-3305
    DOI 10.1186/s13071-019-3526-4
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Different apoptosis pathways in

    Basmaciyan, Louise / Azas, Nadine / Casanova, Magali

    Cell death discovery

    2018  Volume 4, Page(s) 27

    Language English
    Publishing date 2018-08-20
    Publishing country United States
    Document type Editorial
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-018-0092-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: (De)glutamylation and cell death in Leishmania parasites.

    Basmaciyan, Louise / Robinson, Derrick R / Azas, Nadine / Casanova, Magali

    PLoS neglected tropical diseases

    2019  Volume 13, Issue 4, Page(s) e0007264

    Abstract: Trypanosomatids are flagellated protozoan parasites that are very unusual in terms of cytoskeleton organization but also in terms of cell death. Most of the Trypanosomatid cytoskeleton consists of microtubules, forming different substructures including a ...

    Abstract Trypanosomatids are flagellated protozoan parasites that are very unusual in terms of cytoskeleton organization but also in terms of cell death. Most of the Trypanosomatid cytoskeleton consists of microtubules, forming different substructures including a subpellicular corset. Oddly, the actin network appears structurally and functionally different from other eukaryotic actins. And Trypanosomatids have an apoptotic phenotype under cell death conditions, but the pathways involved are devoid of key mammal proteins such as caspases or death receptors, and the triggers involved in apoptotic induction remain unknown. In this article, we have studied the role of the post-translational modifications, deglutamylation and polyglutamylation, in Leishmania. We have shown that Leishmania apoptosis was linked to polyglutamylation and hypothesized that the cell survival process autophagy was linked to deglutamylation. A balance seems to be established between polyglutamylation and deglutamylation, with imbalance inducing microtubule or other protein modifications characterizing either cell death if polyglutamylation was prioritized, or the cell survival process of autophagy if deglutamylation was prioritized. This emphasizes the role of post-translational modifications in cell biology, inducing cell death or cell survival of infectious agents.
    MeSH term(s) Actins/metabolism ; Apoptosis/drug effects ; Cell Survival ; Curcumin/pharmacology ; Cytoskeleton/physiology ; Fluorescent Antibody Technique ; Leishmania/cytology ; Leishmania/drug effects ; Leishmania/genetics ; Microtubules/physiology ; Peptide Synthases/genetics ; Phosphorylcholine/analogs & derivatives ; Phosphorylcholine/pharmacology ; Protein Processing, Post-Translational
    Chemical Substances Actins ; Phosphorylcholine (107-73-3) ; miltefosine (53EY29W7EC) ; Peptide Synthases (EC 6.3.2.-) ; polyglutamyl synthetase (EC 6.3.2.-) ; Curcumin (IT942ZTH98)
    Language English
    Publishing date 2019-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0007264
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities.

    Di Maio, Attilio / Olleik, Hamza / Courvoisier-Dezord, Elise / Guillier, Sophie / Neulat-Ripoll, Fabienne / Haudecoeur, Romain / Bolla, Jean-Michel / Casanova, Magali / Cavalier, Jean-François / Canaan, Stéphane / Pique, Valérie / Charmasson, Yolande / Baydoun, Elias / Hijazi, Akram / Perrier, Josette / Maresca, Marc / Robin, Maxime

    Antibiotics (Basel, Switzerland)

    2024  Volume 13, Issue 4

    Abstract: The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous ... ...

    Abstract The development of new and effective antimicrobial compounds is urgent due to the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules, but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds
    Language English
    Publishing date 2024-03-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics13040300
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Evaluation of the Efficiency of Random and Diblock Methacrylate-Based Amphiphilic Cationic Polymers against Major Bacterial Pathogens Associated with Cystic Fibrosis.

    Casanova, Magali / Olleik, Hamza / Hdiouech, Slim / Roblin, Clarisse / Cavalier, Jean-François / Point, Vanessa / Jeannot, Katy / Caron, Baptiste / Perrier, Josette / Charriau, Siméon / Lafond, Mickael / Guillaneuf, Yohann / Canaan, Stéphane / Lefay, Catherine / Maresca, Marc

    Antibiotics (Basel, Switzerland)

    2023  Volume 12, Issue 1

    Abstract: Cystic fibrosis (CF) is associated with repeated lung bacterial infection, mainly ... ...

    Abstract Cystic fibrosis (CF) is associated with repeated lung bacterial infection, mainly by
    Language English
    Publishing date 2023-01-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics12010120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Calcein+/PI- as an early apoptotic feature in Leishmania.

    Basmaciyan, Louise / Azas, Nadine / Casanova, Magali

    PloS one

    2017  Volume 12, Issue 11, Page(s) e0187756

    Abstract: Although leishmaniases are responsible for high morbidity and mortality all over the world, no really satisfying treatment exists. Furthermore, the corresponding parasite Leishmania undergoes a very characteristic form of programmed cell death. Indeed, ... ...

    Abstract Although leishmaniases are responsible for high morbidity and mortality all over the world, no really satisfying treatment exists. Furthermore, the corresponding parasite Leishmania undergoes a very characteristic form of programmed cell death. Indeed, different stimuli can induce morphological and biochemical apoptotic-like features. However, the key proteins involved in mammal apoptosis, such as caspases and death receptors, are not encoded in the genome of this parasite. Currently, little is known about Leishmania apoptosis, notably owing to the lack of specific tools for programmed cell death analysis in these parasites. Furthermore, there is a need for a better understanding of Leishmania programmed cell death in order (i) to better understand the role of apoptosis in unicellular organisms, (ii) to better understand apoptosis in general through the study of an ancestral eukaryote, and (iii) to identify new therapeutic targets against leishmaniases. To advance understanding of apoptosis in Leishmania, in this study we developed a new tool based on the quantification of calcein and propidium iodide by flow cytometry. This double labeling can be employed to distinguish early apoptosis, late apoptosis and necrosis in Leishmania live cells with a very simple and rapid assay. This paper should, therefore, be of interest for people working on Leishmania and related parasites.
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0187756
    Database MEDical Literature Analysis and Retrieval System OnLINE

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