Role of superoxide dismutase in survival of Leishmania within the macrophage.
TLDR
Results indicate that SOD is a major determinant of intracellular survival of Leishmania, and cloned a SOD gene from L. tropica and generated SOD-deficient parasites by expressing the corresponding antisense RNA from an episomal vector.Abstract:
Intracellular parasitic protozoans of the genus Leishmania depend for their survival on the elaboration of enzymic and other mechanisms for evading toxic free-radical damage inflicted by their phagocytic macrophage host. One such mechanism may involve superoxide dismutase (SOD), which detoxifies reactive superoxide radicals produced by activated macrophages, but the role of this enzyme in parasite survival has not yet been demonstrated. We have cloned a SOD gene from L. tropica and generated SOD-deficient parasites by expressing the corresponding antisense RNA from an episomal vector. Such parasites have enhanced sensitivity to menadione and hydrogen peroxide in axenic culture, and a markedly reduced survival in mouse macrophages. These results indicate that SOD is a major determinant of intracellular survival of Leishmania.read more
Citations
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Subversion Mechanisms by Which Leishmania Parasites Can Escape the Host Immune Response: a Signaling Point of View
TL;DR: Some of the signaling pathways and intermediates that are repressed in infected cells are described, including JAK/STAT, Ca2+-dependent protein kinase C (PKC) isoforms, and mitogen-activated protein kinases (especially ERK1/2), and proteasome-mediated transcription factor degradation.
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Leishmania-macrophage interactions: insights into the redox biology.
TL;DR: A state-of-the-art overview of the redox biology at the parasite-macrophage interface is presented and its involvement in the development of drug resistance and treatment failure are presented.
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Matteo Rossi,Nicolas Fasel +1 more
TL;DR: Host immune response to Leishmania parasites is dominated by T-lymphocytes, which secrete a substance called “ TNF-α” which represses the ability of the immune system to recognize and attack the parasites.
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Mechanisms and consequences of persistence of intracellular pathogens: leishmaniasis as an example.
TL;DR: Parasites of the genus Leishmania have been particular helpful in unravelling some of the basic processes and form therefore the centre of the discussion.
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Human antimicrobial peptide histatin 5 is a cell-penetrating peptide targeting mitochondrial ATP synthesis in Leishmania
TL;DR: Hst5 thus constitutes the first leishmanicidal peptide with a defined nonstereospecific intracellular target and the prospects of its development, by its own or as a carrier molecule for other leish manicidal molecules, into a novel anti‐Leishmania drug with a preferential subcellular accumulation are discussed.
References
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Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels☆
TL;DR: The staining procedure for localizing superoxide dismutase on polyacrylamide electrophoretograms has been applied to extracts obtained from a variety of sources and could thus be assayed either in crude extracts or in purified protein fractions.
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Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase.
Michael U. Shiloh,John D. MacMicking,Susan C. Nicholson,Juliet E. Brause,Strite Potter,Michael W. Marino,Ferric C. Fang,Mary C. Dinauer,Carl Nathan +8 more
TL;DR: Mice doubly deficient in both enzymes formed massive abscesses containing commensal organisms, mostly enteric bacteria, even when reared under specific pathogen-free conditions with antibiotics, establishing the existence of a mechanism of macrophage antibacterial activity independent of phox and NOS2.
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Stable transfection of the human parasite Leishmania major delineates a 30-kilobase region sufficient for extrachromosomal replication and expression.
TL;DR: These data genetically localize all elements required in cis for DNA replication, transcription, and trans splicing to the Leishmania DNA contained within pR-NEO DNA and signal the advent of stable transfection methodology for addressing molecular phenomena in trypanosomatid parasites.
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Iron- and manganese-containing superoxide dismutases can be distinguished by analysis of their primary structures.
TL;DR: Analysis of the aligned amino acid sequences of these enzymes taken together with structural data from X‐ray diffraction studies demonstrates that the two classes of enzyme can be distinguished on the basis of a small number of single‐site substitutions that are positioned in and close to the active site of the enzyme.
Journal ArticleDOI
The role of oxygen and its derivatives in microbial pathogenesis and host defense.
L Beaman,Blaine L. Beaman +1 more
TL;DR: The author reveals how Lysosomes and Oxygen-Independent Microbicidal Mechanisms led to the development of the “plethora of defences” known as “phagocYTIC CELLS”, which were designed to protect against the spread of smallpox.
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