Int J Parasitol. 2011 Apr 7. [Epub ahead of print]
Extracellular Toxoplasma gondii tachyzoites do not require carbon source uptake for ATP maintenance, gliding motility and invasion in the first hour of their extracellular life
Lin SS, Blume M, von Ahsen N, Gross U, Bohne W.
SourceInstitute of Medical Microbiology, University Medical Center Göttingen, Germany.
Abstract
Apicomplexan parasites undergo metabolic shifts in adaptation to environmental changes. Here, we investigate the metabolic requirements which are responsible for ATP homeostasis in the extracellular stage of Toxoplasma gondii. Surprisingly, we found that freshly released tachyzoites are able to maintain a constant ATP level during the first hour of extracellular incubation without the acquisition of external carbon sources. We further demonstrated that the extent of gliding motility and that of host cell invasion is independent from the availability of external carbon sources during this one hour extracellular period. The ATP level and the invasion efficiency of extracellular parasites were severely decreased by treatment with the glycolysis inhibitor, 2-deoxy-d-glucose, but not by the F(0)F(1)-ATPase inhibitor, oligomycin. This suggests that although the uptake of glucose itself is not required during the 1h incubation period, extracellular parasites depend on the activity of the glycolytic pathway for ATP homeostasis. Furthermore, active glycolysis was evident by the secretion of lactate into the culture medium, even in the absence of external carbon sources. Together, our studies suggest that tachyzoites are independent from external carbon sources within the first hour of their extracellular life, which is the most relevant time span for finding a new host cell, but rely on the glycolytic metabolisation of internal carbon sources for ATP maintenance, gliding motility and host cell invasion.
Copyright © 2011. Published by Elsevier Ltd.
PMID:21515276[PubMed - as supplied by publisher]
Wednesday, April 27, 2011
Thursday, April 21, 2011
Jumbled Genomes: Missing Apicomplexan Synteny
Mol Biol Evol. 2011 Apr 19. [Epub ahead of print]
Jumbled Genomes: Missing Apicomplexan Synteny
Debarry JD, Kissinger JC.
SourceCenter for Tropical and Emerging Global Diseases.
Abstract
Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multi-cellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g. malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from 6 genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species and within these conserved regions there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date, and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multi-cellular eukaryotes.
PMID:21504890[PubMed - as supplied by publisher]
Jumbled Genomes: Missing Apicomplexan Synteny
Debarry JD, Kissinger JC.
SourceCenter for Tropical and Emerging Global Diseases.
Abstract
Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multi-cellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g. malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from 6 genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species and within these conserved regions there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date, and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multi-cellular eukaryotes.
PMID:21504890[PubMed - as supplied by publisher]
A Toxoplasma gondii protein with homology to intracellular type Na(+)/H(+) exchangers is important for osmoregulation and invasion
Exp Cell Res. 2011 Apr 9. [Epub ahead of print]
A Toxoplasma gondii protein with homology to intracellular type Na(+)/H(+) exchangers is important for osmoregulation and invasion
Francia ME, Wicher S, Pace DA, Sullivan J, Moreno SN, Arrizabalaga G
SourceDepartment of Biological Sciences, University of Idaho, Life Sciences South Room 142, Moscow, ID 83844, USA.
Abstract
The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na(+)/H(+) exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca(2+) concentration [Ca(2+)](i), and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.
Copyright © 2011. Published by Elsevier Inc.
PMID:21501607[PubMed - as supplied by publisher]
A Toxoplasma gondii protein with homology to intracellular type Na(+)/H(+) exchangers is important for osmoregulation and invasion
Francia ME, Wicher S, Pace DA, Sullivan J, Moreno SN, Arrizabalaga G
SourceDepartment of Biological Sciences, University of Idaho, Life Sciences South Room 142, Moscow, ID 83844, USA.
Abstract
The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na(+)/H(+) exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca(2+) concentration [Ca(2+)](i), and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.
Copyright © 2011. Published by Elsevier Inc.
PMID:21501607[PubMed - as supplied by publisher]
Friday, April 15, 2011
Immune response and protective efficacy against homologous challenge in BALB/c mice vaccinated with DNA vaccine
Vet Parasitol. 2011 Mar 12. [Epub ahead of print]
Immune response and protective efficacy against homologous challenge in BALB/c mice vaccinated with DNA vaccine encoding Toxoplasma gondii actin depolymerizing factor gene
Li J, Huang X, Zhang G, Gong P, Zhang X, Wu L.
College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin 130062, China.
Abstract
A DNA vaccine (pVAX1-TgADF) encoding Toxoplasma gondii actin depolymerizing factor (ADF) gene was constructed and the immune response and protective efficacy of this vaccine against homologous challenge in BALB/c mice were evaluated. High titers of specific antibody and increases in the percentage of CD4(+) and CD8(+) T lymphocyte cells were observed from BALB/c mice vaccinated with pVAX1-TgADF (P<0.05), when PBS group was used as control. The survival time of BALB/c mice in pVAX1-TgADF group was longer than those in control groups. The numbers of brain cysts in the experimental BALB/c mice immunized with pVAX1-TgADF reduced significantly compared with those in PBS group (P<0.05), and the rate of reduction could reach to around 42.8%. These results suggested that the DNA vaccine pVAX1-TgADF could generate specific humoral and cellular immune responses, prolong survival times, and reduce brain cysts load against T. gondii infection in BALB/c mice.
Copyright © 2011 Elsevier B.V. All rights reserved.
PMID: 21489695 [PubMed - as supplied by publisher]
Immune response and protective efficacy against homologous challenge in BALB/c mice vaccinated with DNA vaccine encoding Toxoplasma gondii actin depolymerizing factor gene
Li J, Huang X, Zhang G, Gong P, Zhang X, Wu L.
College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin 130062, China.
Abstract
A DNA vaccine (pVAX1-TgADF) encoding Toxoplasma gondii actin depolymerizing factor (ADF) gene was constructed and the immune response and protective efficacy of this vaccine against homologous challenge in BALB/c mice were evaluated. High titers of specific antibody and increases in the percentage of CD4(+) and CD8(+) T lymphocyte cells were observed from BALB/c mice vaccinated with pVAX1-TgADF (P<0.05), when PBS group was used as control. The survival time of BALB/c mice in pVAX1-TgADF group was longer than those in control groups. The numbers of brain cysts in the experimental BALB/c mice immunized with pVAX1-TgADF reduced significantly compared with those in PBS group (P<0.05), and the rate of reduction could reach to around 42.8%. These results suggested that the DNA vaccine pVAX1-TgADF could generate specific humoral and cellular immune responses, prolong survival times, and reduce brain cysts load against T. gondii infection in BALB/c mice.
Copyright © 2011 Elsevier B.V. All rights reserved.
PMID: 21489695 [PubMed - as supplied by publisher]
Thursday, April 14, 2011
Toxoplasma in Animals, Food, and Humans: An Old Parasite of New Concern
Foodborne Pathog Dis. 2011 Apr 12. [Epub ahead of print]
Toxoplasma in Animals, Food, and Humans: An Old Parasite of New Concern
Cenci-Goga BT, Rossitto PV, Sechi P, McCrindle CM, Cullor JS.
1 Sezione di Ispezione degli Alimenti di Origine Animale, Facoltà di Medicina Veterinaria, Università degli Studi di Perugia , Perugia, Italy .
Abstract
Abstract All hosts, including humans, can be infected by any one of the three forms of the parasite Toxoplasma gondii that correspond to three morphological stages: tachyzoite, bradyzoite, and sporozoite form. Felids are definitive hosts for T. gondii, which is an intracellular pathogen that infects a wide range of warm-blooded intermediate hosts. Toxoplasmosis is a disease where the interest of the diverse medical and veterinary specialties converge. Awareness needs to be increased that toxoplasmosis can induce clinical disease not only in immunocompromised patients or through congenital infections, but also in healthy patients. This is a review article that aims at illustrating why toxoplasmosis should be regarded a veterinary public health issue and how veterinary practitioners can contribute in controlling the infection.
PMID: 21486145 [PubMed - as supplied by publisher]
Toxoplasma in Animals, Food, and Humans: An Old Parasite of New Concern
Cenci-Goga BT, Rossitto PV, Sechi P, McCrindle CM, Cullor JS.
1 Sezione di Ispezione degli Alimenti di Origine Animale, Facoltà di Medicina Veterinaria, Università degli Studi di Perugia , Perugia, Italy .
Abstract
Abstract All hosts, including humans, can be infected by any one of the three forms of the parasite Toxoplasma gondii that correspond to three morphological stages: tachyzoite, bradyzoite, and sporozoite form. Felids are definitive hosts for T. gondii, which is an intracellular pathogen that infects a wide range of warm-blooded intermediate hosts. Toxoplasmosis is a disease where the interest of the diverse medical and veterinary specialties converge. Awareness needs to be increased that toxoplasmosis can induce clinical disease not only in immunocompromised patients or through congenital infections, but also in healthy patients. This is a review article that aims at illustrating why toxoplasmosis should be regarded a veterinary public health issue and how veterinary practitioners can contribute in controlling the infection.
PMID: 21486145 [PubMed - as supplied by publisher]
Wednesday, April 13, 2011
Identification of Novel Proteins in Neospora caninum Using an Organelle Purification and Monoclonal Antibody Approach
PLoS One. 2011 Apr 4;6(4):e18383.
Identification of Novel Proteins in Neospora caninum Using an Organelle Purification and Monoclonal Antibody Approach
Sohn CS, Cheng TT, Drummond ML, Peng ED, Vermont SJ, Xia D, Cheng SJ, Wastling JM, Bradley PJ.
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
Abstract
Neospora caninum is an important veterinary pathogen that causes abortion in cattle and neuromuscular disease in dogs. Neospora has also generated substantial interest because it is an extremely close relative of the human pathogen Toxoplasma gondii, yet does not appear to infect humans. While for Toxoplasma there are a wide array of molecular tools and reagents available for experimental investigation, relatively few reagents exist for Neospora. To investigate the unique biological features of this parasite and exploit the recent sequencing of its genome, we have used an organelle isolation and monoclonal antibody approach to identify novel organellar proteins and develop a wide array of probes for subcellular localization. We raised a panel of forty-six monoclonal antibodies that detect proteins from the rhoptries, micronemes, dense granules, inner membrane complex, apicoplast, mitochondrion and parasite surface. A subset of the proteins was identified by immunoprecipitation and mass spectrometry and reveal that we have identified and localized many of the key proteins involved in invasion and host interaction in Neospora. In addition, we identified novel secretory proteins not previously studied in any apicomplexan parasite. Thus, this organellar monoclonal antibody approach not only greatly enhances the tools available for Neospora cell biology, but also identifies novel components of the unique biological characteristics of this important veterinary pathogen.
PMID: 21483743 [PubMed - in process]
Identification of Novel Proteins in Neospora caninum Using an Organelle Purification and Monoclonal Antibody Approach
Sohn CS, Cheng TT, Drummond ML, Peng ED, Vermont SJ, Xia D, Cheng SJ, Wastling JM, Bradley PJ.
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
Abstract
Neospora caninum is an important veterinary pathogen that causes abortion in cattle and neuromuscular disease in dogs. Neospora has also generated substantial interest because it is an extremely close relative of the human pathogen Toxoplasma gondii, yet does not appear to infect humans. While for Toxoplasma there are a wide array of molecular tools and reagents available for experimental investigation, relatively few reagents exist for Neospora. To investigate the unique biological features of this parasite and exploit the recent sequencing of its genome, we have used an organelle isolation and monoclonal antibody approach to identify novel organellar proteins and develop a wide array of probes for subcellular localization. We raised a panel of forty-six monoclonal antibodies that detect proteins from the rhoptries, micronemes, dense granules, inner membrane complex, apicoplast, mitochondrion and parasite surface. A subset of the proteins was identified by immunoprecipitation and mass spectrometry and reveal that we have identified and localized many of the key proteins involved in invasion and host interaction in Neospora. In addition, we identified novel secretory proteins not previously studied in any apicomplexan parasite. Thus, this organellar monoclonal antibody approach not only greatly enhances the tools available for Neospora cell biology, but also identifies novel components of the unique biological characteristics of this important veterinary pathogen.
PMID: 21483743 [PubMed - in process]
A Novel Toxoplasma gondii Nuclear Factor TgNF3 Is a Dynamic Chromatin-Associated Component, Modulator of Nucleolar Architecture and Parasite Virulence
PLoS Pathog. 2011 Mar;7(3):e1001328. Epub 2011 Mar 31.
A Novel Toxoplasma gondii Nuclear Factor TgNF3 Is a Dynamic Chromatin-Associated Component, Modulator of Nucleolar Architecture and Parasite Virulence
Olguin-Lamas A, Madec E, Hovasse A, Werkmeister E, Callebaut I, Slomianny C, Delhaye S, Mouveaux T, Schaeffer-Reiss C, Van Dorsselaer A, Tomavo S.
Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
Abstract
In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP), known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating nucleosome activities during the intracellular proliferation of the virulent tachyzoites of T. gondii.
PMID: 21483487 [PubMed - in process]
A Novel Toxoplasma gondii Nuclear Factor TgNF3 Is a Dynamic Chromatin-Associated Component, Modulator of Nucleolar Architecture and Parasite Virulence
Olguin-Lamas A, Madec E, Hovasse A, Werkmeister E, Callebaut I, Slomianny C, Delhaye S, Mouveaux T, Schaeffer-Reiss C, Van Dorsselaer A, Tomavo S.
Center for Infection and Immunity of Lille, CNRS UMR 8204, INSERM U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
Abstract
In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP), known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating nucleosome activities during the intracellular proliferation of the virulent tachyzoites of T. gondii.
PMID: 21483487 [PubMed - in process]
Tuesday, April 12, 2011
Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells
PLoS One. 2011 Mar 29;6(3):e18335.
Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells
Wiley M, Teygong C, Phelps E, Radke J, Blader IJ.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Abstract
Toxoplasma gondii is a wide spread pathogen that can cause severe and even fatal disease in fetuses and immune-compromised hosts. As an obligate intracellular parasite, Toxoplasma must alter the environment of its host cell in order to establish its replicative niche. This is accomplished, in part, by secretion of factors into the host cell that act to modulate processes such as transcription. Previous studies demonstrated that genes encoding transcription factors such as c-jun, junB, EGR1, and EGR2 were amongst the host genes that were the most rapidly upregulated following infection. In cells stimulated with growth factors, these genes are regulated by a transcription factor named Serum Response Factor. Serum Response Factor is a ubiquitously expressed DNA binding protein that regulates growth and actin cytoskeleton genes via MAP kinase or actin cytoskeletal signaling, respectively. Here, we report that Toxoplasma infection leads to the rapid activation of Serum Response Factor. Serum Response Factor activation is a Toxoplasma-specific event since the transcription factor is not activated by the closely related protozoan parasite, Neospora caninum. We further demonstrate that Serum Response Factor activation requires a parasite-derived secreted factor that signals via host MAP kinases but independently of the host actin cytoskeleton. Together, these data define Serum Response Factor as a host cell transcription factor that regulates immediate early gene expression in Toxoplasma-infected cells.
PMID: 21479245 [PubMed - as supplied by publisher]
Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells
Wiley M, Teygong C, Phelps E, Radke J, Blader IJ.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Abstract
Toxoplasma gondii is a wide spread pathogen that can cause severe and even fatal disease in fetuses and immune-compromised hosts. As an obligate intracellular parasite, Toxoplasma must alter the environment of its host cell in order to establish its replicative niche. This is accomplished, in part, by secretion of factors into the host cell that act to modulate processes such as transcription. Previous studies demonstrated that genes encoding transcription factors such as c-jun, junB, EGR1, and EGR2 were amongst the host genes that were the most rapidly upregulated following infection. In cells stimulated with growth factors, these genes are regulated by a transcription factor named Serum Response Factor. Serum Response Factor is a ubiquitously expressed DNA binding protein that regulates growth and actin cytoskeleton genes via MAP kinase or actin cytoskeletal signaling, respectively. Here, we report that Toxoplasma infection leads to the rapid activation of Serum Response Factor. Serum Response Factor activation is a Toxoplasma-specific event since the transcription factor is not activated by the closely related protozoan parasite, Neospora caninum. We further demonstrate that Serum Response Factor activation requires a parasite-derived secreted factor that signals via host MAP kinases but independently of the host actin cytoskeleton. Together, these data define Serum Response Factor as a host cell transcription factor that regulates immediate early gene expression in Toxoplasma-infected cells.
PMID: 21479245 [PubMed - as supplied by publisher]
Wednesday, April 06, 2011
Direct evidence of Toxoplasma-induced changes in serum testosterone in mice
Exp Parasitol. 2011 Mar 30. [Epub ahead of print]
Direct evidence of Toxoplasma-induced changes in serum testosterone in mice
Kaňková S, Kodym P, Flegr J.
Department of Philosophy and History of Science, Faculty of Science, Charles University in Prague, Viničná 7, Prague 2, Czech Republic.
Abstract
Latent toxoplasmosis is known to influence the morphology of infected persons and also increases the probability of the birth of male offspring in both humans and mice. All these traits can be related to the observed differences in the concentration of testosterone between Toxoplasma-infected and Toxoplasma-free subjects. However, it is not possible to decide, using the Toxoplasma-human model, whether toxoplasmosis influences the level of testosterone in the infected host or whether individuals with different levels of testosterone vary in the probability of toxoplasma infection. Here we studied changes in the testosterone levels in the latent phase of toxoplasmosis in laboratory mice artificially infected with cystogenic but relatively virulent strain T38 of T. gondii. We observed decreased testosterone levels in both female and male mice with latent toxoplasmosis in comparison to uninfected controls (P = 0.001). The present results indicate that Toxoplasma infection changes the concentration of serum testosterone in mice and human rather than changed concentration of testosterone influences the probability of the Toxoplasma infection. It is possible that the decrease of testosterone is an adaptive mechanism of infected mice aimed to compensate toxoplasmosis-induced immunosuppression observed during latent Toxoplasma infection.
Copyright © 2011. Published by Elsevier Inc.
PMID: 21458453 [PubMed - as supplied by publisher]
Direct evidence of Toxoplasma-induced changes in serum testosterone in mice
Kaňková S, Kodym P, Flegr J.
Department of Philosophy and History of Science, Faculty of Science, Charles University in Prague, Viničná 7, Prague 2, Czech Republic.
Abstract
Latent toxoplasmosis is known to influence the morphology of infected persons and also increases the probability of the birth of male offspring in both humans and mice. All these traits can be related to the observed differences in the concentration of testosterone between Toxoplasma-infected and Toxoplasma-free subjects. However, it is not possible to decide, using the Toxoplasma-human model, whether toxoplasmosis influences the level of testosterone in the infected host or whether individuals with different levels of testosterone vary in the probability of toxoplasma infection. Here we studied changes in the testosterone levels in the latent phase of toxoplasmosis in laboratory mice artificially infected with cystogenic but relatively virulent strain T38 of T. gondii. We observed decreased testosterone levels in both female and male mice with latent toxoplasmosis in comparison to uninfected controls (P = 0.001). The present results indicate that Toxoplasma infection changes the concentration of serum testosterone in mice and human rather than changed concentration of testosterone influences the probability of the Toxoplasma infection. It is possible that the decrease of testosterone is an adaptive mechanism of infected mice aimed to compensate toxoplasmosis-induced immunosuppression observed during latent Toxoplasma infection.
Copyright © 2011. Published by Elsevier Inc.
PMID: 21458453 [PubMed - as supplied by publisher]
Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study
Schizophr Res. 2011 Mar 31. [Epub ahead of print]
Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study
Wang H, Yolken RH, Hoekstra PJ, Burger H, Klein HC.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; Department of Pharmacoepidemiology & Pharmacoeconomics, University of Groningen, 9713 AV Groningen, The Netherlands.
Abstract
Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.
Copyright © 2010 Elsevier B.V. All rights reserved.
PMID: 21458236 [PubMed - as supplied by publisher]
Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study
Wang H, Yolken RH, Hoekstra PJ, Burger H, Klein HC.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; Department of Pharmacoepidemiology & Pharmacoeconomics, University of Groningen, 9713 AV Groningen, The Netherlands.
Abstract
Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.
Copyright © 2010 Elsevier B.V. All rights reserved.
PMID: 21458236 [PubMed - as supplied by publisher]
Identification of the cross-reactive and species-specific antigens between Neospora caninum and Toxoplasma gondii tachyzoites by a proteomics approach
Parasitol Res. 2011 Apr 2. [Epub ahead of print]
Identification of the cross-reactive and species-specific antigens between Neospora caninum and Toxoplasma gondii tachyzoites by a proteomics approach
Zhang H, Lee EG, Yu L, Kawano S, Huang P, Liao M, Kawase O, Zhang G, Zhou J, Fujisaki K, Nishikawa Y, Xuan X.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Abstract
The characterization of the cross-reactive and species-specific antigens of Neospora caninum and Toxoplasma gondii is important in the exploration to determine the common mechanisms of parasite-host interaction and to improve the serological diagnosis; it is also useful for the selection of the cross-reactive antigens that could be used in the development of vaccines or drugs for controlling the diseases caused by these two parasites. In this study, cross-reactive and species-specific antigens between N. caninum and T. gondii tachyzoites were comprehensively investigated using a proteomics approach with the application of two-dimensional gel electrophoresis, immunoblot analysis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS), and MALDI-TOF/TOF-MS analysis. Immunoblotting and mass spectrometry analysis revealed that at least 42 individual protein spots of N. caninum were reacted with the anti-N. caninum serum, among which at least 18 protein spots were cross-reacted with the anti-T. gondii serum. Moreover, at least 31 protein spots of T. gondii were reacted with the anti-T. gondii serum, among which at least 19 protein spots were cross-reacted with the anti-N. caninum serum. Furthermore, some new specific proteins were also identified in the N. caninum protein profile by searching Toxoplasma sequences or sequences from other organisms. This study substantiates the usefulness of proteomics in the immunoscreening of the cross-reactive or species-specific antigens of both parasites. In addition, the present study showed that there was significant homology in the antigenic proteome profiles between the two parasites. These observations have implications for the design of multicomponent common vaccines against both parasite infections.
PMID: 21461729 [PubMed - as supplied by publisher]
Identification of the cross-reactive and species-specific antigens between Neospora caninum and Toxoplasma gondii tachyzoites by a proteomics approach
Zhang H, Lee EG, Yu L, Kawano S, Huang P, Liao M, Kawase O, Zhang G, Zhou J, Fujisaki K, Nishikawa Y, Xuan X.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
Abstract
The characterization of the cross-reactive and species-specific antigens of Neospora caninum and Toxoplasma gondii is important in the exploration to determine the common mechanisms of parasite-host interaction and to improve the serological diagnosis; it is also useful for the selection of the cross-reactive antigens that could be used in the development of vaccines or drugs for controlling the diseases caused by these two parasites. In this study, cross-reactive and species-specific antigens between N. caninum and T. gondii tachyzoites were comprehensively investigated using a proteomics approach with the application of two-dimensional gel electrophoresis, immunoblot analysis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS), and MALDI-TOF/TOF-MS analysis. Immunoblotting and mass spectrometry analysis revealed that at least 42 individual protein spots of N. caninum were reacted with the anti-N. caninum serum, among which at least 18 protein spots were cross-reacted with the anti-T. gondii serum. Moreover, at least 31 protein spots of T. gondii were reacted with the anti-T. gondii serum, among which at least 19 protein spots were cross-reacted with the anti-N. caninum serum. Furthermore, some new specific proteins were also identified in the N. caninum protein profile by searching Toxoplasma sequences or sequences from other organisms. This study substantiates the usefulness of proteomics in the immunoscreening of the cross-reactive or species-specific antigens of both parasites. In addition, the present study showed that there was significant homology in the antigenic proteome profiles between the two parasites. These observations have implications for the design of multicomponent common vaccines against both parasite infections.
PMID: 21461729 [PubMed - as supplied by publisher]
Apicomplexan apicortins possess a long disordered N-terminal extension
Infect Genet Evol. 2011 Apr 1. [Epub ahead of print]
Apicomplexan apicortins possess a long disordered N-terminal extension
Orosz F.
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
Abstract
A new protein, termed apicortin, has recently been identified, which occurs only in the placozoan animal Trichoplax adhaerens and in the genomes of all currently sequenced apicomplexan parasites, (e.g. Toxoplasma, Plasmodium, etc). Apicortins unite two conserved domains, a DCX motif and a partial p25alpha sequence, which are singly found in diverse other proteins, in doublecortins and TPPPs, respectively. Here I show that although apicortin has a limited phylogenomic distribution, its occurrence is broader than thought previously. It has been identified in another primitive opisthokont, in the chytrid fungus, Spizellomyces punctatus. Apicortins can be divided into two subgroups: apicomplexan and non-apicomplexan ones. The main difference is that the former ones possess a long, N-terminal extension predicted to be disordered, which is missing in the other subgroup. The appearance of the extension in apicomplexan apicortins is an "innovation" of this phylum, and may play a functional role in the protein-protein interactions.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21463710 [PubMed - as supplied by publisher]
Apicomplexan apicortins possess a long disordered N-terminal extension
Orosz F.
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
Abstract
A new protein, termed apicortin, has recently been identified, which occurs only in the placozoan animal Trichoplax adhaerens and in the genomes of all currently sequenced apicomplexan parasites, (e.g. Toxoplasma, Plasmodium, etc). Apicortins unite two conserved domains, a DCX motif and a partial p25alpha sequence, which are singly found in diverse other proteins, in doublecortins and TPPPs, respectively. Here I show that although apicortin has a limited phylogenomic distribution, its occurrence is broader than thought previously. It has been identified in another primitive opisthokont, in the chytrid fungus, Spizellomyces punctatus. Apicortins can be divided into two subgroups: apicomplexan and non-apicomplexan ones. The main difference is that the former ones possess a long, N-terminal extension predicted to be disordered, which is missing in the other subgroup. The appearance of the extension in apicomplexan apicortins is an "innovation" of this phylum, and may play a functional role in the protein-protein interactions.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21463710 [PubMed - as supplied by publisher]
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