Wednesday, January 31, 2007

Toxo DnaK and TPR protein 1 mRNA

Toxoplasma gondii mitochondrial DnaK and TPR protein 1 mRNA, complete cds; nuclear gene for mitochondrial product

Roles of bradyzoite-specific surface antigen SRS9

Infect Immun. 2007 Jan 29; [Epub ahead of print]

Bradyzoite-specific surface antigen SRS9 plays a role in maintaining Toxoplasma persistence in the brain and in host control of parasite replication in the intestine

Kim SK, Karasov A, Boothroyd JC.

Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305.

Toxoplasma gondii is an ubiquitous parasite that persists for the life of a healthy mammalian host. A latent, chronic infection can reactivate upon immunosuppression and cause life-threatening diseases, such as encephalitis. A key to the pathogenesis is the parasite's interconversion between the tachyzoite (in acute infection) and bradyzoite (in chronic infection) stages. This developmental switch is marked by differential expression of numerous, closely related surface proteins belonging to the SRS (SAG1-related sequence) superfamily. To probe the functions of bradyzoite-specific SRSs, we created a bioluminescent strain lacking the expression of SRS9, one of the most abundant SRSs of the bradyzoite stage. Imaging of mice intraperitoneally infected with tachyzoites revealed that during an acute infection, wild type and Deltasrs9 strains replicated at similar rates, disseminated systemically following similar kinetics, and initially yielded similar brain cyst numbers. However, during a chronic infection, Deltasrs9 cyst loads substantially decreased compared to the wild type, suggesting that SRS9 plays a role in maintaining parasite persistence in the brain. In oral infection with bradyzoite cysts, the Deltasrs9 strain showed oral infectivity and dissemination patterns indistinguishable from the wild type. When chronically infected mice were treated with an immunosuppressant dexamethasone, however, the Deltasrs9 strain reactivated in the intestinal tissue after only 8-9 days, vs. 2 weeks for the wild type strain. Thus, SRS9 appears to play an important role in both persistence in the brain and reactivation in the intestine. Possible mechanisms for this are discussed.

PMID: 17261600 [PubMed - as supplied by publisher]


Tuesday, January 30, 2007

Identification of a necessary element for SAG1 gene expression

Exp Parasitol. 2007 Jan 25; [Epub ahead of print]

Identification of a necessary element for Toxoplasma gondii SAG1 gene expression

Zhang J, Gu Q, Hou X, Zhou H, Cong H, Li Y, Zhao Q, Li S.

Department of Parasitology, School of Medicine, Shandong University, PR China.

SAG1 codes for the stage-specific major surface antigen P30 of Toxoplasma gondii (T. gondii) tachyzoites. Six tandemly repeated, conserved 27bp cassettes in the region from -231 to -70bp were previously confirmed to be essential for high-level expression of SAG1 and serve as a positioning element directing the initiation of transcription. We demonstrate here that an element located between +19 and +28bp is necessary for SAG1 gene expression by using deletion mutagenesis analysis and electrophoresis mobility shift assay (EMSA). This will provide an insight into the regulatory mechanisms of SAG1 gene expression.

PMID: 17258203 [PubMed - as supplied by publisher]

Saturday, January 27, 2007

Toxo PK1-interactor 1 & cyc2 mRNAs

Toxoplasma gondii PK1-interactor 1 mRNA, partial cds

Toxoplasma gondii Cyc2 (Cyc2) mRNA, complete cds

Friday, January 26, 2007

Toxo glycosylphosphatidylinositols are not involved in host cell survival

Apoptosis. 2007 Jan 25; [Epub ahead of print]

Toxoplasma gondii glycosylphosphatidylinositols are not involved in T. gondii-induced host cell survival.

Debierre-Grockiego F, Hippe D, Schwarz RT, Luder CG.

Institut fur Virologie, AG Parasitologie, Hans-Meerwein-Str. 2, D-35043, Marburg, Germany,

Toxoplasma gondii is an intracellular parasite able to both promote and inhibit apoptosis. T. gondii renders infected cells resistant to programmed cell death induced by multiple apoptotic triggers. On the other hand, increased apoptosis of immune cells after in vivo infection with T. gondii may suppress the immune response to the parasite. Glycosylphosphatidylinositol (GPI)-anchored proteins dominate the surface of T. gondii tachyzoites and GPIs are involved in the pathogenicity of protozoan parasites. In this report, we determine if GPIs are responsible for inhibition or induction of host cell apoptosis. We show here that T. gondii GPIs fail to block apoptosis that was triggered in human-derived cells via extrinsic or intrinsic apoptotic pathways. Furthermore, characteristics of apoptosis, e.g. caspase-3/7 activity, phosphatidylserine exposition at the cell surface or DNA strand breaks, were not observed in the presence of T. gondii GPIs. These results indicate that T. gondii GPIs are not involved in survival or in apoptosis of host cells. This absence of effect on apoptosis could be a feature common to GPIs of other parasites.

PMID: 17252196 [PubMed - as supplied by publisher]

Thursday, January 25, 2007

Toxo infection and reactive arthritis

J Postgrad Med. 2007 Jan-Mar;53(1):14-6.

Is there any relationship between toxoplasma infection and reactive arthritis?

Sert M, Ozbek S, Paydas S, Yaman A.

Cukurova University, Medical Faculty, Dept. of Internal Medicine, 01330 Adana, Turkey.

BACKGROUND: The diagnosis of reactive arthritis is a challenging clinical problem in daily practice. Although there are many triggering infectious agents for reactive arthritis, Toxoplasmosis, a worldwide parasitic infection has not been reported. AIM: We investigated the serologic evidence of Toxoplasma gondii ( T. gondii ) infection in patients with newly diagnosed reactive arthritis after six weeks of the onset of the first symptom but no demonstrable triggering agent for reactive arthritis. Setting and Design: Clinical controlled study. MATERIALS AND METHODS: We screened serologically the serum toxoplasma IgM and IgG antibody (Ab) titers which revealed toxoplasma infection in 50 patients with reactive arthritis (40 female, 10 men) and no demonstrable triggering agent and control subjects (32 female, 8 male). STATISTICAL ANALYSIS: SPSS 10.0 software package program was used. RESULTS: The mean age of the patients and controls was similar (41.3+/- 12.0 vs. 39.6+/-11.8 years) respectively. The prevalence of IgG Ab titers of T. gondii in patients and controls were found to be 52% and 47.5%, respectively. Mean serum Toxoplasma IgG Ab levels were found to be 16.5+/-14.5 IU/ml, and 16.9+/-13.8 IU/ml in patients and control subjects respectively ( P> 0.05). We did not find any Toxoplasma IgM Ab titer demonstrating the acute or sub-acute infection in the serum of patients or controls. CONCLUSION: Although past Toxoplasma infection was prevalent in both groups, we did not find any subject with acute Toxoplasma infection in patients with newly diagnosed reactive arthritis and healthy controls. Despite the fact that our study group was small, we suggest that T. gondii does not seem to be a triggering agent for reactive arthritis and past infection may be a coincidental finding.

PMID: 17244964 [PubMed - in process]

Wednesday, January 24, 2007

Substrate analogs induce an intermediate conformational change in Toxo adenosine kinase

Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):126-34. Epub 2007 Jan 16.

Substrate analogs induce an intermediate conformational change in Toxoplasma gondii adenosine kinase

Zhang Y, El Kouni MH, Ealick SE.

Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.

Adenosine kinase (AK) is a key enzyme in purine metabolism in the ubiquitous intracellular parasite Toxoplasma gondii and is a potential chemotherapeutic target for the treatment of T. gondii infections. To better understand the structure-activity relationship of 6-substituted purine ribosides, the structures of the T. gondii AK-N(6),N(6)-dimethyladenosine (DMA) complex, the AK-DMA-AMP-PCP complex, the AK-6-methyl mercaptopurine riboside (MMPR) complex and the AK-MMPR-AMP-PCP complex were determined to 1.35, 1.35, 1.75 and 1.75 A resolution, respectively. These structures reveal a conformation intermediate between open and closed, with a small lid-domain rotation of 12 degrees . Residues Gly143-X-X-Gly146 undergo torsional changes upon substrate binding, which together with a Gly68-Gly69 switch induces a hinge bending of the lid domain. The intermediate conformation suggests that ATP binding is independent of adenosine binding. Orienting the gamma-phosphate group of ATP into the optimal catalytic position may be the last step before the onset of chemical catalysis and may require the translocation of Arg136 following the complete closure of the lid domain. 6-Substituted purine-nucleoside analogs are accommodated in a hydrophobic cavity. Modification at the N(6) or C6 position of the nucleoside would affect the interactions with the surrounding residues and the binding affinity.

PMID: 17242506 [PubMed - in process]

Effect of High Affinity Inhibitor of Alternative (type II) NADH Dehydrogenases on Toxo

Antimicrob Agents Chemother. 2007 Jan 22; [Epub ahead of print]

Growth inhibition of Toxoplasma gondii and Plasmodium falciparum by Nanomolar Concentrations of HDQ (1-hydroxy-2-dodecyl-4(1H)quinolone): a High Affinity Inhibitor of Alternative (type II) NADH Dehydrogenases.

Saleh A, Friesen J, Baumeister S, Gross U, Bohne W.

Institute of Medical Microbiology, University of Gottingen, Kreuzbergring 57, Gottingen D-37075; Germany; FB Biologie/Parasitologie, Philipps-Universitat Marburg, Karl von Frisch Strasse 8, D-35032 Marburg; Germany.

Both apicomplexan parasites Toxoplasma gondii and Plasmodium falciparum lack type I NADH dehydrogenases (complex I), but instead encode alternative (type II) NADH dehydrogenases, which are absent in mammalian cells and are thus considered as promising antimicrobial drug targets. The quinolone-like compound 1-hydroxy-2-dodecyl-4(1)quinolone (HDQ) was recently described as a high affinity inhibitor of fungal alternative NADH-dehydrogenases in enzymatic assays, probably by interfering with the ubiquinol binding site of the enzyme. We describe here that HDQ effectively inhibits the replication rate of P. falciparum and T. gondii in tissue culture. The IC50 of HDQ was determined for T. gondii at 2.4 +/- 0.3 nM with a growth assay based on vacuole sizes and at 3.7 +/- 1.4 nM with a growth assay based on beta-galactosidase activity. Quantification of P. falciparum replication rate using a fluorometric assay revealed an IC50 of 14.0 nM +/- 1.9. An important feature of the HDQ structure is the length of the alkyl side chain at position 2. Derivatives with alkyl side chains of C6, C8, C12 (HDQ) and C14 all displayed excellent anti-T. gondii activity, while a C5 derivative completely failed to inhibit parasite replication. A combined treatment of T. gondii infected cells with HDQ and the antimalarial agent atovaquone, which blocks the ubiquinol oxidation site of cytochrom b in complex III, resulted in synergism with a calculated FIC of 0.16 nM. An interference of the mitochondrial ubiquinone/ubiquinol cycle at two different locations thus appears to be a highly effective strategy to inhibit parasite replication. HDQ and its derivatives represent particularly in combination with atovaquone promising compounds with high potential for antimalarial and antitoxoplasmal therapy.

PMID: 17242151 [PubMed - as supplied by publisher]


Epilepsy and seropositivity rates of Toxocara canis and Toxo

Seizure. 2007 Jan 16; [Epub ahead of print]

Epilepsy and seropositivity rates of Toxocara canis and Toxoplasma gondii

Akyol A, Bicerol B, Ertug S, Ertabaklar H, Kiylioglu N.

Adnan Menderes University, Medical Faculty, Department of Neurology, 09100 Aydin, Turkey.

PURPOSE: Increased seropositivity for Toxoplasma gondii and Toxocara canis have been observed in epileptic patients. Our aim is to determine whether there is any relationship between these agents and epilepsy in our cryptogenic epilepsy group. MATERIAL AND METHODS: We studied specific IgG antibodies against T. gondii and T. canis in 100 cryptogenic epileptic patients and 50 healthy volunteers that had no history of epilepsy in their first degree relatives. We studied T. gondii and T. canis-specific IgG antibody serum levels and compared the values of these two groups. RESULT: We found similar T. gondii and T. canis serum IgG antibodies in patients with cryptogenic epilepsy and in the control group, even though the control group included more animal owners. CONCLUSION: We did not show any relationships between epilepsy and positive T. gondii and T. canis serology in our epileptic patients.

PMID: 17239629 [PubMed - as supplied by publisher]

Betamethasone and invasion of tachyzoites

Iran J Allergy Asthma Immunol. 2006 Jun;5(2):75-8.

The Effect of Betamethasone and IFN-gamma Toxoplasma gondii (RH Strain) and Nitric Oxide Production in HeLa Cell Culture

Ghaffarifar F, Dalimi Asl A, Sharifi Z, Ghasemi S, Solhjoo K, Roodbar Mohammadi S.

Department of Parasitology, Faculty of Medicine, Tarbiat Modares University of Medical Sciences, Tehran, Iran.

Toxoplasmosis is a protozoal infection caused by Toxoplasma gondii. Toxoplasmosis produce severe damage in patients who are immunosuppresed. In those who are immunosupressed, latent infection can be reactivated resulting in acute disseminating disease. Betamethasone is a synthetic glycocorticoid, used as an anti-inflamatory and immunosuppressant in a wide variety of disorders.The aim of this study was evaluation of betamethasone as an immunosuppressor drug on infected cells by Toxoplasma gondii. In this study, at first HeLa cells were grown in 24 well culture plates in culture medium .When confluent monolayer was obtained, we compared 6 groups to evaluate the effect of betamethasone as a corticosteroid drug (two concentrations 4 and 40mug/ml) and the effect of IFN-gamma (100 IU/ml ) on growth, replication and Nitric Oxide (NO) production. The results showed, that high number of plaques were seen in group with 40 mug/ml of betamethasone and the lowest number of plaques were seen in group with 100 IU of IFN-gamma. The difference between plaque number in control and groups treated with IFN-gamma and betamethasone was significant (P<0.05). The groups with betamethasone or IFN-gamma without tachyzoites did not show any effect on cell structures. Replication rates in the wells treated with IFN-gamma were decreased significantly 72h post inoculation in comparison with control group (P<0.05). There was no significant difference among different groups in NO production. The results indicated that betamethasone increase the invasion of tachyzoites to host cells in vitro.

PMID: 17237580 [PubMed - in process]

Toxo mRNA for Pdx1 and Pdx2 protein

Toxoplasma gondii mRNA for Pdx2 protein

Toxoplasma gondii mRNA for Pdx1 protein

Tuesday, January 23, 2007

Infection with Bradyzoites Has a Diminished Impact on Host Transcript Levels Relative to Tachyzoite Infection

Infection and Immunity, February 2007, p. 634-642, Vol. 75, No. 20019-9567

Infection with Toxoplasma gondii Bradyzoites Has a Diminished Impact on Host Transcript Levels Relative to Tachyzoite Infection

A. E. Fouts and J. C. Boothroyd

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-51241

Toxoplasma gondii, an intracellular pathogen, has the potential to infect nearly every warm-blooded animal but rarely causes morbidity. The ability for the parasite to convert to the bradyzoite stage and live inside slow-growing cysts that can go unnoticed by the host immune system allows for parasite persistence for the life of the infected host. This intracellular survival likely necessitates host cell modulation, and tachyzoites are known to modify a number of signaling cascades within the host to promote parasite survival. Little is known, however, about how bradyzoites manipulate their host cell. Microarrays were used to profile the host transcriptional changes caused by bradyzoite infection and compared to those of tachyzoite-infected and uninfected hosts cells 2 days postinfection in vitro. Infection resulted in chemokine, cytokine, extracellular matrix, and growth factor transcript level changes. A small group of genes were specifically induced by tachyzoite infection, including granulocyte-macrophage colony-stimulating factor, BCL2-related protein A1, and interleukin-24. Bradyzoite infection yielded only about half the changes seen with tachyzoite infection, and those changes that did occur were almost all of lower magnitude than those induced by tachyzoites. These results suggest that bradyzoites lead a more stealthy existence within the infected host cell.


Thursday, January 18, 2007

Cytokine regulation of immunopathology in toxoplasmosis

Immunol Cell Biol. 2007 Jan 16; [Epub ahead of print]

Cytokine regulation of immunopathology in toxoplasmosis.

Gaddi PJ, Yap GS.

1Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.

Toxoplasma gondii infection is an important cause of central nervous system and ocular disease, both in immunocompromised and in certain immunocompetent populations. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immuno-sufficient individuals. In this review, we have critically evaluated the body of experimental evidence indicating a role of CD4 T cells in systemic and local immunopathology associated with T. gondii infection. We also discuss the pathogenic roles of cytokines produced by T helper (Th) 1 and Th17 cells and the protective and homeostatic roles of interleukin (IL)-10, transforming growth factor-beta and IL-27 in modulating hypersensitivity responses induced by T. gondii. Immunology and Cell Biology advance online publication, 16 January 2007; doi:10.1038/sj.icb.7100038.

PMID: 17228318 [PubMed - as supplied by publisher]

Toxo inhibits Fas/CD95-triggered cell death

Toxoplasma gondii inhibits Fas/CD95-triggered cell death by inducing aberrant processing and degradation of caspase 8

Polya Vutova, Martina Wirth, Diana Hippe, Uwe Gross, Klaus Schulze-Osthoff, Ingo Schmitz, Carsten G. K. Lüder

Accepted article online: 15-Jan-2007

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Golgi biogenesis in simple eukaryotes

Cell Microbiol. 2007 Jan 11; [Epub ahead of print]

Golgi biogenesis in simple eukaryotes.

He CY.

Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8002, USA.

The accurate duplication of cellular organelles is important to ensure propagation through successive generations. The semi-conserved replication of DNA and DNA-containing organelles has been well studied, but the mechanisms used to duplicate most other organelles remain elusive. These include the centrosomes, which act as microtubule organizing centres during interphase and orient the mitotic spindle poles during mitosis. Centrosomes can also act as basal bodies, nucleating the growth of cilia or flagella. Even less understood are the mechanisms used to duplicate membrane-bound organelles that do not contain DNA. These include organelles involved in the secretory pathway such as the endoplasmic reticulum and the Golgi apparatus. This review will summarize the current knowledge of Golgi biogenesis in simple eukaryotic organisms, in particular, two protozoan parasites, Toxoplasma gondii and Trypanosoma brucei.

PMID: 17223925 [PubMed - as supplied by publisher]

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CD40-TRAF6 and Autophagy-Dependent Anti-Microbial Activity in Macprophages

Autophagy. 2007 May 15;3(3) [Epub ahead of print]

CD40-TRAF6 and Autophagy-Dependent Anti-Microbial Activity in Macprophages.

Subauste CS, Andrade RM, Wessendarp M.

Departments of Ophthalmology and Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.

A fundamental question in host-pathogen interaction is to determine if the immune system activates fusion with the lysosomes to eradicate pathogens. We recently reported that this task is accomplished by the interaction between CD40 expressed on macrophages and CD154 expressed on activated CD4(+) T cells. CD40 stimulation of macrophages induces vacuole-lysosome fusion through autophagy and results in killing of the obligate intracellular pathogen Toxoplasma gondii. This response is independent of IFN-gamma, STAT1 and p47 GTPases. We now report that vacuole-lysosome fusion is dependent on synergy between TRAF6 signaling downstream of CD40 and TNF-alpha. These studies identified a new paradigm by which T cells eradicate an intracellular pathogen within macrophages.

PMID: 17224624 [PubMed - as supplied by publisher]

Wednesday, January 17, 2007

Toxo researchers spot the difference

Nature Reviews Microbiology 5, 86 (February 2007) doi:10.1038/nrmicro1607

Parasitology: Toxo researchers spot the difference

Sheilagh Molloy

An estimated one billion people are infected with Toxoplasma gondii worldwide, and in Europe and North America there are just three dominant clonal lineages. Despite sharing 98% genetic identity, the three lineages — types I, II and III — differ greatly in virulence. Now, a trio of papers reveal that just a handful of genes are responsible for these differences.

In two papers in Science, Sonya Taylor, Antonio Barragan, Chunlei Su and colleagues, and Jeroen Saeij, John Boyle and colleagues used forward genetic mapping to identify the genes responsible for the strain-specific differences in virulence. In mice, type I strains are more virulent than types II and III. Taylor et al. undertook genome-wide quantitative trait loci (QTL) mapping of the F1 progeny of a genetic cross between a type I and a type III strain. They found an association between virulence and a region on chromosome VIIa, and this was narrowed down to the ROP18 gene, which encodes the ROP18 protein. ROP18 is found in the rhoptries, specialised apical organelles that are unique to apicomplexans, and contains a conserved serine kinase domain. Taylor et al. confirmed that this protein is a functional kinase and is secreted into host cells. Importantly, transfer of the type I allele into the non-virulent type III lineage decreased the lethal dose by more than 4 logs.

Virulence is a multigenic trait and crossing the less virulent type II and type III strains generates some F1 progeny in which the virulence is greatly enhanced. Saeij and colleagues therefore chose to use QTL mapping in such progeny to identify loci involved in virulence. A total of five virulence loci were identified, including one on chromosome VIIa, which was found to correspond to ROP18, and one on chromosome VIIb, which corresponded to a gene encoding another rhoptry kinase, ROP16.

Rhoptry protein kinases seem to have an important role in T. gondii virulence. What are their cellular targets? This question was addressed by Jeroen Saeij, Susan Coller and colleagues in Nature. In this work, ROP16 was again identified as a key modulator of the host response, this time by a completely different approach that involved the use of microarrays to identify which genes in the F1 progeny of a cross between a type II and a type III strain had a strong effect on gene expression in human cells. Further detailed work revealed that the three clonal lineages differ in their level of activation of the STAT signalling pathway (and therefore the crucial cytokine interleukin 12), and that ROP16 is involved in this effect.

So, analagous to bacterial pathogens and their secretion systems, it seems that these eukaryotic pathogens can secrete protein kinases into host cells to subvert host-cell signalling pathways and that this explains many of the differences in virulence among the three dominant clonal lineages.

References and links

Taylor, S. et al. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314, 1776–1780 (2006)

Saeij, J. P. J. et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314, 1780–1783 (2006)

Saeij, J. P. et al. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 20 Dec 2006 (doi: 10.1038/nature05395)

Tuesday, January 16, 2007

Effects of Toxo on Human Behavior

Schizophr Bull. 2007 Jan 11; [Epub ahead of print]

Effects of Toxoplasma on Human Behavior

Flegr J.

Dept of Parasitology, Faculty of Science, Charles University, Vinicna 7, CZ-128 44 Praha 2, Czech Republic.

Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. The demonstration that latent Toxoplasma infections can alter behavior in rodents has led to a reconsideration of this assumption. When infected human adults were compared with uninfected adults on personality questionnaires or on a panel of behavioral tests, several differences were found. Other studies have demonstrated reduced psychomotor performance in affected individuals. Possible mechanisms by which T. gondii may affect human behavior include its effect on dopamine and on testosterone.

PMID: 17218612 [PubMed - as supplied by publisher]

Effect of Toxo on Animal Behavior

Schizophr Bull. 2007 Jan 11; [Epub ahead of print]

The Effect of Toxoplasma gondii on Animal Behavior: Playing Cat and Mouse.

Webster JP.

2Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, St Mary's Hospital Campus, Norfolk Place, London, UK.

A convincing body of evidence now exists to indicate that the ubiquitous protozoan Toxoplasma gondii can cause permanent behavioral changes in its host, even as a consequence of adult-acquired latent infection. Such behavioral alterations appear to be the product of strong selective pressures for the parasite to enhance transmission from its intermediate host reservoir, primarily rodent, to its feline definitive host, wherein sexual reproduction can occur and the life cycle completed. This article reviews evidence of behavioral alterations in animal hosts and considers what these may elucidate about the potential mechanisms involved and what implications such alterations could have on animal and human health.

PMID: 17218613 [PubMed - as supplied by publisher]

Toxo generates pyridoxal phosphate de novo

Mol Biochem Parasitol. 2006 Dec 20; [Epub ahead of print]

The apicomplexan parasite Toxoplasma gondii generates pyridoxal phosphate de novo.

Knockel J, Muller IB, Bergmann B, Walter RD, Wrenger C.

Bernhard Nocht Institute for Tropical Medicine, Department of Biochemistry, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany.

PMID: 17222923 [PubMed - as supplied by publisher]

Full text here

Impairment of helper T cell responses to immunodominant epitopes of Toxo antigens in congenital infections

Microbes Infect. 2006 Dec 6; [Epub ahead of print]

Age-dependent impairment of functional helper T cell responses to immunodominant epitopes of Toxoplasma gondii antigens in congenitally infected individuals.

Guglietta S, Beghetto E, Spadoni A, Buffolano W, Del Porto P, Gargano N.

Department of Cellular and Developmental Biology, University of Rome "La Sapienza", Via dei Sardi 70, 00185 Rome, Italy.

Human infection with Toxoplasma gondii is generally asymptomatic in immunocompetent adults while it causes significant morbidity in congenitally infected children. Cell mediated immunity plays the main role in host resistance to T. gondii infection and a Th1 cytokine profile is necessary for protection and control of infection. The present work focused on comparing the helper T cell response to the GRA1 antigen of the parasite between children with congenital toxoplasmosis and healthy adults with acquired infection. We demonstrated that in young children with congenital infection the specific T cell response to parasite antigens is impaired and that such hypo-responsiveness is restored during childhood. Also, we provided clear evidence that in individuals with congenital toxoplasmosis the acquisition of functional helper T cell responses is disease-unrelated and indistinguishable in terms of strength, epitope specificity, and cytokine profile from the corresponding responses in immunocompetent adults with asymptomatic acquired T. gondii infection.

PMID: 17223600 [PubMed - as supplied by publisher]

Thursday, January 11, 2007

Antibodies to Infectious Agents in Individuals at Ultra-High Risk for Psychosis

Biol Psychiatry. 2007 Jan 2; [Epub ahead of print]

Antibodies to Infectious Agents in Individuals at Ultra-High Risk for Psychosis.

Amminger GP, McGorry PD, Berger GE, Wade D, Yung AR, Phillips LJ, Harrigan SM, Francey SM, Yolken RH.

ORYGEN Research Centre (incorporating the Personal Assistance and Crises Evaluation [PACE] Clinic), Department of Psychiatry, University of Melbourne, Australia; Department of Child and Adolescent Psychiatry, Medical University of Vienna, Austria.

BACKGROUND: While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis. METHODS: Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures. RESULTS: Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses. CONCLUSIONS: In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.

PMID: 17207471 [PubMed - as supplied by publisher],17205696

Toxo myosin light chains 2 & 3 mRNAs

Toxoplasma gondii myosin light chain 3 mRNA, complete cds

Toxoplasma gondii myosin light chain 2 mRNA, complete cds

Wednesday, January 10, 2007

Toxo Protein Phosphatase 2C targets host cell nuclei

Toxoplasma gondii Targets a Protein Phosphatase 2C to the Nuclei of Infected Host Cells

Luke A. Gilbert, Sandeep Ravindran, Jay M. Turetzky, John C.
Boothroyd, and Peter J. Bradley

Eukaryotic Cell 2007;6 73-83

Thursday, January 04, 2007

Toxo macrophage migration inhibitory factor mRNA

Toxoplasma gondii MIF mRNA, complete cds