المؤلفون: Eberhardt, Ayelen T.¹ aeberhardt@fcv.unl.edu.ar, Costa, Sebastián A.¹, Marini, M. Rocío², Racca, Andrea¹, Baldi, Cecilia J.¹, Robles, M. Rosario³, Moreno, Pablo G.¹, Beldomenico, Pablo M.¹

المصدر: PLoS ONE. Jul2013, Vol. 8 Issue 7, p1-12. 12p.

مصطلحات موضوعية: *CAPYBARA, *IMMUNOLOGY, *NATURAL immunity, *HOST-parasite relationships, *ZOOLOGICAL research, *MAMMALOGY, PARASITE physiology

مستخلص: Parasites play a key role in regulating wildlife population dynamics, but their impact on the host appears to be context-dependent. Evidence indicates that a synergistic interaction between stress, host condition and parasites is implicated in this phenomenon, but more studies are needed to better understand this context-dependency. With the goal to assess the net effect of two types of chronic stress on various host-parasite interactions, we conducted an experiment in capybaras to evaluate the impact of food restriction and physical restraint on the infection intensity of specific gastrointestinal nematodes and coccidia, and how these stressors affected the growth, body condition, and some immuno-physiological parameters. Our hypothesis was that both forms of stress would result in an alteration in the host-parasite interactions, with deteriorated condition and reduced immunological investment leading to high parasite burdens and vice versa. Stressed capybaras had significantly higher coccidia infection intensities; but among individuals that were smaller, those stressed consistently showed lower helminth burdens than controls. Both stress treatments had a marked negative impact on growth and body condition, but concomitantly they had a significant positive effect on some components of the immune system. Our results suggest, on the one hand, that during prolonged periods of stress capybaras preventatively invest in some components of their immunity, such as innate humoural defenses and cells that combat helminths, which could be considered a stress-dependent prophylaxis. On the other hand, stress was found to cause greater infection intensities of protozoans but lower burdens of nematodes, indicating that the relationship between stress, physiological trade-offs and infection depends on the type of parasite in question. Moreover, both findings might be related in a causal way, as one of the immunological parameters enhanced in stressed capybaras is associated with the immune response to control helminths. [ABSTRACT FROM AUTHOR]

المؤلفون: Mark O. Collins, Jyoti S. Choudhary, Frank Schwach, David A. Baker, Oliver Billker, Mathieu Brochet, Sarah Sebastian, Eloise Thompson, Terry K. Smith, Julian C. Rayner, Katrin Volkmann, Lia Chappell, Ana Rita Gomes, Matthew Berriman

المصدر: PLoS Biology

مصطلحات موضوعية: Gliding motility, Pathogenesis, Signal transduction, Phosphatidylinositols, Molecular cell biology, Crosstalk, Second Messenger System, Calcium signaling, biology, Protein Kinase Signaling Cascade, Kinase, General Neuroscience, Mechanisms of Signal Transduction, Signaling Cascades, 3. Good health, Cell biology, Cyclic GMP-Dependent Protein Kinases, Host-Pathogen Interaction, Biochemistry, cardiovascular system, General Agricultural and Biological Sciences, Research Article, Signaling in cellular processes, Plasmodium falciparum, Phosphoinositide Signal Transduction, Microbiology, Signaling Pathways, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Host-Parasite Interactions, parasitic diseases, Calcium-Mediated Signal Transduction, Animals, Humans, Plasmodium berghei, Calcium Signaling, Protein kinase A, Biology, Life Cycle Stages, General Immunology and Microbiology, Parasite Physiology, biology.organism_classification, Malaria, Culicidae, Cell movement signaling, Phospholipid Signaling Cascade, Calcium Signaling Cascade, cGMP signaling, Parasitology, cGMP-dependent protein kinase

الوصف: Chemical genetics and a global comparative analysis of phosphorylation and phospholipids in vivo shows that PKG is the upstream regulator that induces calcium signals that enables Plasmodium to progress through its complex life cycle.
Many critical events in the Plasmodium life cycle rely on the controlled release of Ca2+ from intracellular stores to activate stage-specific Ca2+-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP)-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca2+ required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca2+ signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5)-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca2+ effectors, PKG emerges as a unifying factor to control multiple cellular Ca2+ signals essential for malaria parasite development and transmission.
Author Summary Malaria, caused by Plasmodium spp. parasites, is a profound human health problem. Plasmodium parasites progress through a complex life cycle as they move between infected humans and blood-feeding mosquitoes. We know that tight regulation of calcium ion levels within the cytosol of the parasite is critical to control multiple signalling events in their life cycle. However, how these calcium levels are controlled remains a mystery. Here, we show that a single protein kinase, the cGMP-dependent protein kinase G (PKG), controls the calcium signals that are critical at three different points of the life cycle: (1) for the exit of the merozoite form of the parasite from human erythrocytes (red blood cells), (2) for the cellular activation that happens when Plasmodium sexual transmission stages are ingested by a blood-feeding mosquito, and (3) for the productive gliding of the ookinete, which is the parasite stage that invades the mosquito midgut. We provide initial evidence that the universal role of PKG relies on the production of lipid precursors which then give rise to inositol (1,4,5)-trisphosphate (IP3), a messenger molecule that serves as a signal for the release of calcium from stores within the parasite. This signalling pathway provides a potential target to block both malaria development in the human host and transmission to the mosquito vector.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c792bb6c970837aeed6d45c3e4297437Test
http://europepmc.org/articles/PMC3942320Test

المؤلفون: Guillermina García-Rivera, Lorenza González-Mariscal, Michael Schnoor, Cecilia Bañuelos, Rosario Javier-Reyna, Abigail Betanzos, Esther Orozco

المصدر: PLoS ONE
PLoS ONE, Vol 8, Iss 6, p e65100 (2013)

مصطلحات موضوعية: Protozoan Proteins, lcsh:Medicine, Apoptosis, Pathogenesis, Occludin, Madin Darby Canine Kidney Cells, Molecular Cell Biology, Claudin-1, Gastrointestinal Infections, lcsh:Science, Multidisciplinary, biology, Tight junction, Virulence, Entamoeba histolytica, Amebiasis, Cell biology, Host-Pathogen Interaction, Protein Transport, Infectious Diseases, Medicine, Cellular Types, Research Article, Neglected Tropical Diseases, Protein Binding, Infectious Disease Control, Gastroenterology and Hepatology, Protein degradation, Microbiology, Models, Biological, Epithelial Damage, Necrosis, Dogs, Cell Adhesion, Parasitic Diseases, Autophagy, Animals, Humans, Immunoprecipitation, Trophozoites, Claudin, Biology, Microbial Pathogens, Protozoan Infections, lcsh:R, Parasite Physiology, Epithelial Cells, biology.organism_classification, Molecular biology, Membrane protein, Caco-2, lcsh:Q, Parasitology, Caco-2 Cells, Parasitic Intestinal Diseases

الوصف: Entamoeba histolytica, the protozoan responsible for human amoebiasis, causes between 30,000 and 100,000 deaths per year worldwide. Amoebiasis is characterized by intestinal epithelial damage provoking severe diarrhea. However, the molecular mechanisms by which this protozoan causes epithelial damage are poorly understood. Here, we studied the initial molecular interactions between the E. histolytica EhCPADH112 virulence complex and epithelial MDCK and Caco-2 cells. By confocal microscopy, we discovered that after contact with trophozoites or trophozoite extracts (TE), EhCPADH112 and proteins forming this complex (EhCP112 and EhADH112) co-localize with occludin and claudin-1 at tight junctions (TJ). Immunoprecipitation assays revealed interaction between EhCPADH112 and occludin, claudin-1, ZO-1 and ZO-2. Overlay assays confirmed an interaction of EhCP112 and EhADH112 with occludin and claudin-1, whereas only EhADH112 interacted also with ZO-2. We observed degradation of all mentioned TJ proteins after incubation with TE. Importantly, inhibiting proteolytic activity or blocking the complex with a specific antibody not only prevented TJ protein degradation but also epithelial barrier disruption. Furthermore, we discovered that TE treatment induces autophagy and apoptosis in MDCK cells that could contribute to the observed barrier disruption. Our results suggest a model in which epithelial damage caused by E. histolytica is initiated by the interaction of EhCP112 and EhADH112 with TJ proteins followed by their degradation. Disruption of TJs then induces increased paracellular permeability, thus facilitating the entry of more proteases and other parasite molecules leading eventually to tissue destruction.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f82de3a18ce60cd02c9eaddd03af0fdTest
http://europepmc.org/articles/PMC3676397Test

المؤلفون: Laetitia Minguez, Nelly Brulé, Simon Devin, Bénédicte Sohm, Laure Giamberini

المساهمون: Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

المصدر: PLoS ONE
PLoS ONE, Vol 8, Iss 6, p e65822 (2013)
PLoS ONE, Public Library of Science, 2013, 8 (6), ⟨10.1371/journal.pone.0065822⟩

مصطلحات موضوعية: Male, Programmed cell death, Anatomy and Physiology, Histology, Science, Apoptosis, 010501 environmental sciences, Biology, 01 natural sciences, Microbiology, Dreissena, Host-Parasite Interactions, 03 medical and health sciences, Heat shock protein, Bucephalus polymorphus, Molecular Cell Biology, Parasite hosting, Animals, HSP70 Heat-Shock Proteins, 030304 developmental biology, 0105 earth and related environmental sciences, Cellular Stress Responses, 0303 health sciences, Multidisciplinary, TUNEL assay, Cell Death, Intracellular parasite, Parasite Physiology, biology.organism_classification, 3. Good health, Cell biology, Hsp70, Host-Pathogen Interaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: HEAT-SHOCK PROTEINS, PROGRAMMED CELL-DEATH, DREISSENA-POLYMORPHA, ANAPLASMA-PHAGOCYTOPHILUM, EHRLICHIA-CHAFFEENSIS, CRASSOSTREA-VIRGINICA, BACTERIAL PATHOGENS, DIGESTIVE GLAND, IMMUNE-SYSTEM, OSTREA-EDULIS, [SDE]Environmental Sciences, Medicine, Parasitology, Female, Physiological Processes, Zoology, Research Article

الوصف: International audience; The question of whether cell death by apoptosis plays a biological function during infection is key to understanding host-parasite interactions. We investigated the involvement of apoptosis in several host-parasite systems, using zebra mussels Dreissena polymorpha as test organisms and their micro-and macroparasites. As a stress response associated with parasitism, heat shock proteins (Hsp) can be induced. In this protein family, Hsp70 are known to be apoptosis inhibitors. Mussels were diagnosed for their respective infections by standard histological methods; apoptosis was detected using the TUNEL methods on paraffin sections and Hsp70 by immunohistochemistry on cryosections. Circulating hemocytes were the main cells observed in apoptosis whereas infected tissues displayed no or few apoptotic cells. Parasitism by intracellular bacteria Rickettsiales-like and the trematode Bucephalus polymorphus were associated with the inhibition of apoptosis whereas ciliates Ophryoglena spp. or the trematode Phyllodistomum folium did not involve significant differences in apoptosis. Even if some parasites were able to modulate apoptosis in zebra mussels, we did not see evidence of any involvement of Hsp70 on this mechanism.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d10253427b65470fc86a33a3263a37fTest
http://europepmc.org/articles/PMC3681881Test

المؤلفون: M. Rosario Robles, Pablo G. Moreno, Andrea Racca, Ayelen T. Eberhardt, M. Rocío Marini, Sebastian Costa, Pablo Martín Beldomenico, Cecilia J. Baldi

المصدر: PLoS ONE, Vol 8, Iss 7, p e70382 (2013)
SEDICI (UNLP)
Universidad Nacional de La Plata
instacron:UNLP
PLoS ONE
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET

مصطلحات موضوعية: Biología, Population Dynamics, lcsh:Medicine, Hydrochaeris hydrochaeris, Otras Ciencias Veterinarias, Chronic stress, lcsh:Science, Immune Response, education.field_of_study, Multidisciplinary, Animal Behavior, Innate Immunity, Host-Pathogen Interaction, Mammalogy, Ciencias Agrícolas, Research Article, Immunology, Population, Zoology, Parasitism, Rodentia, Capybara meat, Biology, Microbiology, Host-Parasite Interactions, Immune system, Coccidia, DISEASE ECOLOGY, Immunity, VICIOUS CIRCLE, Helminths, Animal Physiology, Animals, Disease Dynamics, education, HOST-PARASITE RELATIONSHIP, Population Biology, Ciencias Veterinarias, Stressor, lcsh:R, Parasite Physiology, biology.organism_classification, Immunity, Innate, Parasitology, lcsh:Q, purl.org/becyt/ford/4.3 [https], purl.org/becyt/ford/4 [https]

الوصف: Parasites play a key role in regulating wildlife population dynamics, but their impact on the host appears to be context-dependent. Evidence indicates that a synergistic interaction between stress, host condition and parasites is implicated in this phenomenon, but more studies are needed to better understand this context-dependency. With the goal to assess the net effect of two types of chronic stress on various host-parasite interactions, we conducted an experiment in capybaras to evaluate the impact of food restriction and physical restraint on the infection intensity of specific gastrointestinal nematodes and coccidia, and how these stressors affected the growth, body condition, and some immuno-physiological parameters. Our hypothesis was that both forms of stress would result in an alteration in the host-parasite interactions, with deteriorated condition and reduced immunological investment leading to high parasite burdens and vice versa. Stressed capybaras had significantly higher coccidia infection intensities; but among individuals that were smaller, those stressed consistently showed lower helminth burdens than controls. Both stress treatments had a marked negative impact on growth and body condition, but concomitantly they had a significant positive effect on some components of the immune system. Our results suggest, on the one hand, that during prolonged periods of stress capybaras preventatively invest in some components of their immunity, such as innate humoural defenses and cells that combat helminths, which could be considered a stress-dependent prophylaxis. On the other hand, stress was found to cause greater infection intensities of protozoans but lower burdens of nematodes, indicating that the relationship between stress, physiological trade-offs and infection depends on the type of parasite in question. Moreover, both findings might be related in a causal way, as one of the immunological parameters enhanced in stressed capybaras is associated with the immune response to control helminths.
Centro de Estudios Parasitológicos y de Vectores

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c66a7645cee4fd1afa0779eba43b7a12Test
http://europepmc.org/articles/PMC3722164?pdf=renderTest

المؤلفون: Kyoko Hayashida, Makoto Kuroda, Chihiro Sugimoto, Atsushi Ito, Tomohiro Yamazaki, Hiroki Nagai, Mitsutaka Yoshida, Shinji Nakamura, Tsuyoshi Sekizuka, Fumihiko Takeuchi, Hiroyuki Yamaguchi, Kasumi Ishida, Yasuhiro Hayashi, Junji Matsuo, Kaori Takahashi

المصدر: PLoS ONE, Vol 8, Iss 2, p e56005 (2013)
PLoS ONE

مصطلحات موضوعية: Virulence Factors, Poly ADP ribose polymerase, Science, Lactacystin, Molecular Sequence Data, Caspase 3, Apoptosis, Biology, Mitochondrion, Bioenergetics, Protozoology, Biochemistry, Microbiology, Cell Line, chemistry.chemical_compound, Model Organisms, Endopeptidases, Molecular Cell Biology, Humans, Amino Acid Sequence, Chlamydia, Parasite Evolution, Energy-Producing Organelles, Cytopathic effect, Caspase-9, Evolutionary Biology, Multidisciplinary, Cell Death, Parasite Physiology, Molecular biology, Caspase 9, Cell biology, Mitochondria, Host-Pathogen Interaction, chemistry, Cell culture, Proteolysis, biology.protein, Medicine, Parasitology, Poly(ADP-ribose) Polymerases, Sequence Alignment, Research Article

الوصف: Obligate amoebal endosymbiotic bacterium Protochlamydia with ancestral pathogenic chlamydial features evolved to survive within protist hosts, such as Acanthamoba, 0.7-1.4 billion years ago, but not within vertebrates including humans. This observation raises the possibility that interactions between Protochlamydia and human cells may result in a novel cytopathic effect, leading to new insights into host-parasite relationships. Previously, we reported that Protochlamydia induces apoptosis of the immortalized human cell line, HEp-2. In this study, we attempted to elucidate the molecular mechanism underlying this apoptosis. We first confirmed that, upon stimulation with the bacteria, poly (ADP-ribose) polymerase (PARP) was cleaved at an early stage in HEp-2 cells, which was dependent on the amount of bacteria. A pan-caspase inhibitor and both caspase-3 and -9 inhibitors similarly inhibited the apoptosis of HEp-2 cells. A decrease of the mitochondrial membrane potential was also confirmed. Furthermore, lactacystin, an inhibitor of chlamydial protease-like activity factor (CPAF), blocked the apoptosis. Cytochalasin D also inhibited the apoptosis, which was dependent on the drug concentration, indicating that bacterial entry into cells was required to induce apoptosis. Interestingly, Yersinia type III inhibitors (ME0052, ME0053, and ME0054) did not have any effect on the apoptosis. We also confirmed that the Protochlamydia used in this study possessed a homologue of the cpaf gene and that two critical residues, histidine-101 and serine-499 of C. trachomatis CPAF in the active center, were conserved. Thus, our results indicate that after entry, Protochlamydia-secreted CPAF induces mitochondrial dysfunction with a decrease of the membrane potential, followed by caspase-9, caspase-3 and PARP cleavages for apoptosis. More interestingly, because C. trachomatis infection can block the apoptosis, our finding implies unique features of CPAF between pathogenic and primitive chlamydiae.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::adc3a013a5509b31282ecccb9cf3c985Test
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23409113/?tool=EBITest

المؤلفون: Tavis K. Anderson, Nathan A. Peterson, Timothy P. Yoshino

المصدر: PLoS ONE, Vol 8, Iss 5, p e63299 (2013)
PLoS ONE

مصطلحات موضوعية: Physiogenomics, Mouse, In silico, Cloning, Organism, Science, Sequence alignment, Helminth genetics, Biology, Microbiology, Homology (biology), 03 medical and health sciences, Model Organisms, Parasitic Diseases, Gene family, Schistosomiasis, Animals, Parasite Evolution, Gene, 030304 developmental biology, Genomic organization, Genetics, 0303 health sciences, Genome, Helminth, Multidisciplinary, 030302 biochemistry & molecular biology, Alternative splicing, Parasite Physiology, Genomics, Animal Models, Helminth Proteins, Schistosoma mansoni, Comparative Genomics, Fucosyltransferases, 3. Good health, Host-Pathogen Interaction, Infectious Diseases, Medical Microbiology, Multigene Family, Medicine, Parasitology, Research Article

الوصف: Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae78d3cf138ae03e76da3647338e7145Test
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23696810/?tool=EBITest

المؤلفون: Célia Maria de Almeida Soares, Ana Flávia Alves Parente, Simone Schneider Weber, Clayton Luiz Borges, Juliana Alves Parente, Alexandre Melo Bailão

المصدر: PLoS ONE
PLoS ONE, Vol 7, Iss 12, p e52470 (2012)

مصطلحات موضوعية: Proteomics, Male, Proteome, Fungal Physiology, lcsh:Medicine, Yeast and Fungal Models, Biochemistry, Paracoccidioides, chemistry.chemical_compound, Mice, Yeasts, Molecular Cell Biology, Protein Isoforms, lcsh:Science, Fungal protein, Multidisciplinary, Spectrometric Identification of Proteins, Fungal Diseases, Brefeldin A, Host-Pathogen Interaction, Infectious Diseases, Medicine, Research Article, Signal peptide, Mycology, Biology, Microbiology, Fungal Proteins, Model Organisms, Phagocytosis, Cell Adhesion, Animals, Mycelium, Macrophages, lcsh:R, Parasite Physiology, Yeast, Enzyme Activation, Secretory protein, Metabolism, chemistry, lcsh:Q, Parasitology, Protein Processing, Post-Translational, Protein Abundance

الوصف: Paracoccidioides, a complex of several phylogenetic species, is the causative agent of paracoccidioidomycosis. The ability of pathogenic fungi to develop a multifaceted response to the wide variety of stressors found in the host environment is important for virulence and pathogenesis. Extracellular proteins represent key mediators of the host-parasite interaction. To analyze the expression profile of the proteins secreted by Paracoccidioides, Pb01 mycelia and yeast cells, we used a proteomics approach combining two-dimensional electrophoresis with matrix-assisted laser desorption ionization quadrupole time-of-flight mass spectrometry (MALDI-Q-TOF MS/MS). From three biological replicates, 356 and 388 spots were detected, in mycelium and yeast cell secretomes, respectively. In this study, 160 non-redundant proteins/isoforms were indentified, including 30 and 24 proteins preferentially secreted in mycelia and yeast cells, respectively. In silico analyses revealed that 65% of the identified proteins/isoforms were secreted primarily via non-conventional pathways. We also investigated the influence of protein export inhibition in the phagocytosis of Paracoccidioides by macrophages. The addition of Brefeldin A to the culture medium significantly decreased the production of secreted proteins by both Paracoccidioides and internalized yeast cells by macrophages. In contrast, the addition of concentrated culture supernatant to the co-cultivation significantly increased the number of internalized yeast cells by macrophages. Importantly, the proteins detected in the fungal secretome were also identified within macrophages. These results indicate that Paracoccidioides extracellular proteins are important for the fungal interaction with the host.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89c80f3cf7256183b048db27571eaaa1Test
http://europepmc.org/articles/PMC3525554Test

المؤلفون: Pragyan Acharya, Utpal Tatu, Shweta Chaubey, Manish Grover

المصدر: PLoS ONE
PLoS ONE, Vol 7, Iss 9, p e44605 (2012)

مصطلحات موضوعية: Erythrocytes, Immunoprecipitation, viruses, Molecular Sequence Data, Plasmodium falciparum, lcsh:Medicine, KAHRP, Pathogenesis, Biochemistry, Microbiology, 03 medical and health sciences, Heat shock protein, parasitic diseases, Molecular Cell Biology, Animals, Humans, Amino Acid Sequence, lcsh:Science, Protein Interactions, Fluorescent Antibody Technique, Indirect, Peptide sequence, Biology, 030304 developmental biology, Cellular Stress Responses, 0303 health sciences, Multidisciplinary, biology, lcsh:R, 030302 biochemistry & molecular biology, Parasite Physiology, Proteins, HSP40 Heat-Shock Proteins, Translocon, biology.organism_classification, Virology, 3. Good health, Cell biology, Chaperone Proteins, Host-Pathogen Interaction, Emerging Infectious Diseases, Cytoplasm, Chaperone (protein), biology.protein, lcsh:Q, Parasitology, Membranes and Sorting, Research Article

الوصف: Cell surface structures termed knobs are one of the most important pathogenesis related protein complexes deployed by the malaria parasite Plasmodium falciparum at the surface of the infected erythrocyte. Despite their relevance to the disease, their structure, mechanisms of traffic and their process of assembly remain poorly understood. In this study, we have explored the possible role of a parasite-encoded Hsp40 class of chaperone, namely PFB0090c/PF3D7_0201800 (KAHsp40) in protein trafficking in the infected erythrocyte. We found the gene coding for PF3D7_0201800 to be located in a chromosomal cluster together with knob components KAHRP and PfEMP3. Like the knob components, KAHsp40 too showed the presence of PEXEL motif required for transport to the erythrocyte compartment. Indeed, sub-cellular fractionation and immunofluorescence analysis (IFA) showed KAHsp40 to be exported in the erythrocyte cytoplasm in a stage dependent manner localizing as punctuate spots in the erythrocyte periphery, distinctly from Maurer's cleft, in structures which could be the reminiscent of knobs. Double IFA analysis revealed co-localization of PF3D7_0201800 with the markers of knobs (KAHRP, PfEMP1 and PfEMP3) and components of the PEXEL translocon (Hsp101, PTEX150). KAHsp40 was also found to be in a complex with KAHRP, PfEMP3 and Hsp101 as confirmed by co-immunoprecipitation assay. Our results suggest potential involvement of a parasite encoded Hsp40 in chaperoning knob assembly in the erythrocyte compartment.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3c0944f6ffd6853df560aa5ec4772f7Test
http://europepmc.org/articles/PMC3436795Test

المؤلفون: Nathalie Boilard, Marie-Noelle Chou, Conan Chow, Barbara Papadopoulou, Serge Cloutier, Maxime Laverdière

المصدر: PLoS ONE
PLoS ONE, Vol 7, Iss 5, p e35085 (2012)

مصطلحات موضوعية: Eukaryotic Initiation Factor-2, lcsh:Medicine, Protozoology, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Eukaryotic translation, Stress, Physiological, Polysome, Phagosomes, Molecular Cell Biology, Protein biosynthesis, Parasitic Diseases, Animals, Leishmania infantum, Phosphorylation, lcsh:Science, Amastigote, Biology, Leishmaniasis, 030304 developmental biology, Cellular Stress Responses, Regulation of gene expression, 0303 health sciences, Multidisciplinary, biology, Macrophages, lcsh:R, Parasite Physiology, Microbial Growth and Development, Temperature, Gene Expression Regulation, Developmental, Translation (biology), Hydrogen-Ion Concentration, biology.organism_classification, Leishmania, Adaptation, Physiological, Cell biology, Host-Pathogen Interaction, Infectious Diseases, Protein Biosynthesis, Parastic Protozoans, Medicine, lcsh:Q, Parasitology, 030217 neurology & neurosurgery, Research Article

الوصف: The parasitic protozoan Leishmania alternates between an invertebrate and a mammalian host. Upon their entry to mammalian macrophages, Leishmania promastigotes differentiate into amastigote forms within the harsh environment of the phagolysosomal compartment. Here, we provide evidence for the importance of translational control during the Leishmania differentiation process. We find that exposure of promastigotes to a combined elevated temperature and acidic pH stress, a key signal triggering amastigote differentiation, leads to a marked decrease in global translation initiation, which is associated with eIF2α phosphorylation. Interestingly, we show that amastigotes adapted to grow in a cell-free medium exhibit lower levels of protein synthesis in comparison to promastigotes, suggesting that amastigotes have to enter a slow growth state to adapt to the stressful conditions encountered inside macrophages. Reconversion of amastigotes back to promastigote growth results in upregulation of global translation and a decrease in eIF2α phosphorylation. In addition, we show that while general translation is reduced during amastigote differentiation, translation of amastigote-specific transcripts such as A2 is preferentially upregulated. We find that A2 developmental gene regulation is triggered by temperature changes in the environment and that occurs mainly at the level of translation. Upon elevated temperature, the A2 transcript is stabilized through its association with polyribosomes leading to high levels of translation. When temperature decreases during amastigote to promastigote differentiation, the A2 transcript is not longer associated with translating polyribosomes and is being gradually degraded. Overall, these findings contribute to our better understanding of the adaptive responses of Leishmania to stress during its development and highlight the importance of translational control in promastigote to amastigote differentiation and vice-versa.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eaf45d326b410ef435c5a947a81f9cd2Test
http://europepmc.org/articles/PMC3365078Test