Author
Louise Basmaciyan
Other affiliations: Aix-Marseille University
Bio: Louise Basmaciyan is an academic researcher from University of Burgundy. The author has contributed to research in topics: Programmed cell death & Cryptosporidium. The author has an hindex of 11, co-authored 28 publications receiving 289 citations. Previous affiliations of Louise Basmaciyan include Aix-Marseille University.
Topics: Programmed cell death, Cryptosporidium, Leishmania, Apoptosis, Autophagy
Papers
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TL;DR: In this paper, the authors provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions' attack by pathogens, including bacteria, viruses, fungi, and parasites.
Abstract: Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions’ attack by pathogens, including bacteria, viruses, fungi, and parasites.
65 citations
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TL;DR: A novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains, identifying the most potent antimalarial candidates with selectivity index (SI) of 40.6 on W2 strain, and 39.25 on 3D6 strain.
Abstract: Novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC50 in the μM range. In attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward Leishmania donovani were also investigated and revealed their selective antiplasmodial profile. In parallel, the in vitro cytotoxicity of these molecules was assessed on the human HepG2 cell line. Structure-activity relationships of these new synthetic compounds are discussed here. The bis-pyrrolo[1,2-a]quinoxalines 1n and 1p were identified as the most potent antimalarial candidates with selectivity index (SI) of 40.6 on W2 strain, and 39.25 on 3D7 strain, respectively. As the telomeres of the parasite could constitute an attractive target, we investigated the possibility of targeting Plasmodium telomeres by stabilizing the Plasmodium telomeric G-quadruplexes through a FRET melting assay by our new compounds.
51 citations
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TL;DR: An overview of the current knowledge regarding the mechanisms of pathogenicity that allow the fungus to reach and translocate the gut barrier is provided.
Abstract: Formerly a commensal organism of the mucosal surfaces of most healthy individuals, Candida albicans is an opportunistic pathogen that causes infections ranging from superficial to the more life-threatening disseminated infections, especially in the ever-growing population of vulnerable patients in the hospital setting. In these situations, the fungus takes advantage of its host following a disturbance in the host defense system and/or the mucosal microbiota. Overwhelming evidence suggests that the gastrointestinal tract is the main source of disseminated C. albicans infections. Major risk factors for disseminated candidiasis include damage to the mucosal intestinal barrier, immune dysfunction, and dysbiosis of the resident microbiota. A better understanding of C. albicans' interaction with the intestinal epithelial barrier will be useful for designing future therapies to avoid systemic candidiasis. In this review, we provide an overview of the current knowledge regarding the mechanisms of pathogenicity that allow the fungus to reach and translocate the gut barrier.
47 citations
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TL;DR: Two models are proposed, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains.
Abstract: Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine-cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H2O2, LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains.
33 citations
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TL;DR: An overview of the current knowledge on Leishmania cell death is provided, describing its physiological roles and its phenotype, and the involvement of various proteins: endonuclease G, metacaspase, aquaporin Li-BH3AQP, calpains, cysteine proteinase C, LmJHYD36 and Lmj.22.0600 are discussed.
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.
32 citations
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05 Oct 2017
TL;DR: This work identifies the first, to the authors' knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans, which directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity.
Abstract: Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name ‘Candidalysin’ for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.
453 citations
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TL;DR: It is discussed how the new findings have the potential to transform the understanding of TJ structure and function, and how the intricate network of TJ proteins and membrane lipids dynamically interact to drive TJ assembly.
218 citations
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TL;DR: The success of Trichoderma spp.
177 citations
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University of Graz1, Spanish National Research Council2, Providence College3, University of Sheffield4, University of Malta5, Tel Aviv University6, University of Miami7, Brown University8, French Institute of Health and Medical Research9, University of Bayreuth10, Roswell Park Cancer Institute11, Stockholm University12, University of Florence13, University Medical Center Groningen14, Rowan University15, University of Minho16, Instituto de Biologia Molecular e Celular17, University of Porto18, University of Bordeaux19, University of New South Wales20, University of Fribourg21, Texas A&M University22, Université libre de Bruxelles23, University of Lausanne24, National Research Council25, University of Parma26, University of Kent27, University of Manchester28, Royal Military College of Canada29, University of Osnabrück30, Heinrich Pette Institute31, Kaiserslautern University of Technology32, University of Alcalá33, University of Texas MD Anderson Cancer Center34, RMIT University35, University of Milano-Bicocca36, Sapienza University of Rome37, University of Ottawa38, Ottawa Hospital Research Institute39, University of Freiburg40, Technical University of Denmark41, Chalmers University of Technology42, University of Gothenburg43, Goethe University Frankfurt44, Ohio State University45, Centre national de la recherche scientifique46, Comenius University in Bratislava47, University of Minnesota48, University of Exeter49, University of Salzburg50, University of Kassel51, University of Málaga52, Moscow State University53, Free University of Berlin54, Katholieke Universiteit Leuven55, Concordia University56, Université Paris-Saclay57, Heidelberg University58, University of Wyoming59, University of Maryland, Baltimore60, Tsinghua University61, Cornell University62, Paris Descartes University63
TL;DR: Unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria are proposed.
Abstract: Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel-lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the defi-nition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differ-ential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death rou-tines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the au-thors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the pro-gress of this vibrant field of research.
134 citations
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TL;DR: The virulence traits of Candida albicans and clinical manifestations of specific candidiasis are discussed in this paper. But, the authors do not consider the effect of these virulence factors on the development of specific Candida infections.
Abstract: Candida albicans is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals' skin. In 50% of the population, C. albicans is part of the normal flora of the microbiota. The various clinical manifestations of Candida species range from localized, superficial mucocutaneous disorders to invasive diseases that involve multiple organ systems and are life-threatening. From systemic and local to hereditary and environmental, diverse factors lead to disturbances in Candida's normal homeostasis, resulting in a transition from normal flora to pathogenic and opportunistic infections. The transition in the pathophysiology of the onset and progression of infection is also influenced by Candida's virulence traits that lead to the development of candidiasis. Oral candidiasis has a wide range of clinical manifestations, divided into primary and secondary candidiasis. The main supply of C. albicans in the body is located in the gastrointestinal tract, and the development of infections occurs due to dysbiosis of the residential microbiota, immune dysfunction, and damage to the muco-intestinal barrier. The presence of C. albicans in the blood is associated with candidemia-invasive Candida infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of C. albicans. This paper presents the virulence traits of Candida albicans and clinical manifestations of specific candidiasis.
100 citations