Tuesday, July 31, 2007

Endemic avian toxoplasmosis on a farm in Illinois

Vet Parasitol. 2007 Jul 24; [Epub ahead of print]

Endemic avian toxoplasmosis on a farm in Illinois: Clinical disease, diagnosis, biologic and genetic characteristics of Toxoplasma gondii isolates from chickens (Gallus domesticus), and a goose (Anser anser)

Dubey JP, Webb DM, Sundar N, Velmurugan GV, Bandini LA, Kwok OC, Su C.

United States Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Animal Parasitic Diseases Laboratory, Building 1001, Beltsville, MD 20705-2350, USA.

Clinical toxoplasmosis in chickens (Gallus domesticus) has been rarely reported in literature. Here we report that three chickens on a farm in Illinois developed neurological signs. One of these chickens was examined postmortem and it had non-suppurative encephalitis with numerous Toxoplasma gondii tachyzoites and tissue cysts. The identity of the protozoa was confirmed immunohistochemically by staining with T. gondii specific antibodies, and by transmission electron microscopy. The owner of the 3 chickens donated all 11 remaining chickens and a goose on his property for the present study. All 11 chickens and a goose were euthanized, and blood, heart, brain, and 1 leg were obtained for T. gondii examination. Antibodies to T. gondii were found in sera of all chickens with titers of 1:40 in one, 1:320 in three, and 1:640 or higher in seven chickens tested by the modified agglutination test (MAT). The goose had a MAT titer of 1:320. For isolation of T. gondii, whole heart and brain and 50g of leg muscles were digested in an acid-pepsin solution and bioassayed in four mice for each tissue. Viable T. gondii was isolated from tissues of all 11 chickens and the goose. Genotyping of these 12 T. gondii isolates using polymorphism at the genetic loci SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, a new SAG2 and Apico revealed that all isolates had Type II alleles at all loci, indicating these T. gondii isolates belong to the predominant clonal Type II lineages. This is the first report of isolation of viable T. gondii from a domestic goose (Anser anser).

PMID: 17656021 [PubMed - as supplied by publisher]

Serum protein alterations in dogs naturally infected with Toxo

Parasitol Res. 2007 Jul 22; [Epub ahead of print]

Serum protein alterations in dogs naturally infected with Toxoplasma gondii

Yarim GF, Nisbet C, Oncel T, Cenesiz S, Ciftci G

Department of Biochemistry, Faculty of Veterinary Medicine, University of Ondokuz Mayis, 55139, Kurupelit, Samsun, Turkey, gulyarim@omu.edu.tr.

We conducted this study to describe the serum electrophoretic pattern in dogs associated with the infection of Toxoplasma gondii (T. gondii). The serum protein pattern of 25 dogs with confirmed T. gondii infection and 15 clinically healthy dogs were evaluated using native polyacrylamide gel electrophoresis. Albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin bands were seen from the serum electrophoresis of infected and healthy dogs. Compared to the control group, significant decreases in the mean percentages of albumin (from 46.1 +/- 7.2 to 40.8 +/- 4.5%, P < 0.05), alpha-1 globulin (from 3.9 +/- 0.4 to 0.8 +/- 0.2%, P < 0.001), alpha-2 globulin (from 9.0 +/- 0.4 to 8.3 +/- 0.8%, P < 0.01), and beta globulin (from 18.4 +/- 1.2 to 12.1 +/- 0.6%, P < 0.001) in the infected group were determined. In contrast, gamma globulin fraction was significantly higher in infected dogs (38.1 +/- 4.6%) than in control dogs (22.7 +/- 7.2%; P < 0.001). Moreover, significant correlations were determined between the percentages of the albumin and gamma globulin fractions and liver enzyme tests including aspartate aminotransferase and alanine aminotransferase in infected dogs; however, no correlation was observed for the other protein fractions. In conclusion, marked alterations in serum protein pattern associated with strong modifications of serum protein concentrations are in accordance with the hepatic injury as affirmed by liver enzyme tests that were demonstrated in the canine toxoplasmosis. These findings showed that serum protein electrophoresis can be used in the diagnosis and prognosis of canine toxoplasmosis as a supplementary analysis in combination with serological, clinical, and laboratory findings of this disease.

PMID: 17659389 [PubMed - as supplied by publisher]

Leucine Rich Repeat Protein binds Phosphatase type 1 protein and negatively regulates its activity

Eukaryot Cell. 2007 Jul 27; [Epub ahead of print]

A Toxoplasma gondii Leucine Rich Repeat Protein binds Phosphatase type 1 protein and negatively regulates its activity

Daher W, Oria G, Fauquenoy S, Cailliau K, Browaeys E, Tomavo S, Khalife J.

From the Unité Inserm 547/IPL, Institut Pasteur, 1 rue du Pr Calmette, B.P. 245, 59019 Lille cedex, France, Equipe de Parasitologie Moléculaire, CNRS UMR 8576, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France, UPRES EA 1033, IFR 118, SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.

We have characterized the Toxoplasma gondii protein phosphatase type 1, TgPP1, and a potential regulatory binding protein belonging to the Leucine Rich Repeat protein family designated TgLRR1. TgLRR1 is capable of binding to TgPP1, to inhibit its activity, and to override a G2/M cell-cycle checkpoint in Xenopus oocytes. In the parasite, TgLRR1 mRNA and protein are both highly expressed in the rapidly replicating and virulent tachyzoites while only low levels are detected in the slowly dividing and quiescent bradyzoites. TgPP1 mRNA and protein levels are equally abundant in tachyzoites and bradyzoites. Affinity-pull down and immunoprecipitation experiments reveal that the interaction TgLRR1-TgPP1 takes place in the nuclear sub-compartment of tachyzoites. These results are consistent with localization studies using both indirect immunofluorescence with specific polyclonal antibody and transient transfection of T. gondii vector expressing TgLRR1 and TgPP1. The inability of obtaining stable transgenic tachyzoites suggested that overexpression of TgLRR1 and TgPP1 may impair the parasite's growth. Together with the activation of Xenopus oocytes meiosis re-initiation, these data indicate that TgLRR1 protein could play a role in the regulation of the T. gondii cell cycle through modulation of phosphatase activity.

PMID: 17660360 [PubMed - as supplied by publisher]

Friday, July 27, 2007

Microglia Produce IFN-gamma Independently from T Cells During Acute Toxoplasmosis in the Brain

J Interferon Cytokine Res. 2007 Jul;27(7):599-605

Microglia Produce IFN-gamma Independently from T Cells During Acute Toxoplasmosis in the Brain

Wang X, Suzuki Y.
Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

We previously reported a requirement of interferon-gamma (IFN-gamma) production by both T cells and cells other than T or natural killer (NK) cells in the brain for prevention of toxoplasmic encephalitis. In the present study, we examined whether microglia, the resident macrophage system in the brain, produce IFN-gamma in response to infection with Toxoplasma gondii in SCID and wild-type BALB/c mice. IFN-gamma was detected in the culture supernatants of microglia purified from the brains of SCID mice that had developed toxoplasmic encephalitis due to reactivation of infection. A significant increase in numbers of IFN-gamma-expressing microglia was also observed by immunostaining for this cytokine in the brains of SCID and BALB/c mice during the acute stage of acquired infection, and those numbers decreased in the later stage of infection in the BALB/c animals. These results indicate that microglia produce IFN-gamma in the presence and absence of T cells in response to reactivated or acute acquired infection in the brain. Because IFN-gamma is the essential effector molecule to control tachyzoites and because this cytokine is a potent inducer of expression of chemokines and MHC antigens important for recruitment and activation of T cells, IFN-gamma production by microglia might play a critical role in the early stage of tachyzoite proliferation in the brain by limiting parasite growth and initiating subsequent T cell immunity.

PMID: 17651021 [PubMed - in process]

Influence of latent toxoplasmosis on the secondary sex ratio in mice

Parasitology. 2007 Jul 26;:1-9 [Epub ahead of print]

Influence of latent toxoplasmosis on the secondary sex ratio in mice

Kaňková S, Kodym P, Frynta D, Vavřinová R, Kuběna A, Flegr J.
Department of Parasitology, Faculty of Science, Charles University in Prague, Viničná 7, CZ-128 44 Prague 2, Czech Republic.

SUMMARYThe sex ratio may be influenced by many factors, such as stress and immunosuppression, age of parents, parity and sex of preceding siblings. In animal systems, parasitism often changes the sex ratio of infected hosts, which can increase the probability of their transmission. The most common human protozoan parasite in developed countries, Toxoplasma gondii (prevalence 20%-80%), is known to change the behaviour of its intermediate hosts, thereby increasing the probability of transmission to its definitive host (the cat) by predation. The intermediate hosts, which under natural conditions are rodents, serve as the vector for Toxoplasma. Therefore, we speculate that Toxoplasma can alter the secondary sex ratio (i.e. male to female ratio in the offspring) of infected females to increase the proportion of (congenitally infected) male offspring, which are the more migratory sex in most rodent species. Here we studied the sex ratio of experimentally infected laboratory mice, expressed here as the proportion of males in the litter. In accordance with our hypothesis and results of previous retrospective cohort studies on human subjects, mice with toxoplasmosis produced a higher sex ratio than controls, in the early phase of latent infection. In the later phase of infection, mice with congenital toxoplasmosis had a lower sex ratio than controls, which is in accord with the Trivers-Willard hypothesis of sex ratio manipulation, suggesting that females in poor physical condition give birth to more female offspring.

PMID: 17651529 [PubMed - as supplied by publisher]

Wednesday, July 25, 2007

Toxo mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity

Mol Biochem Parasitol. 2007 Jun 19; [Epub ahead of print]

A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity

Lavine MD, Knoll LJ, Rooney PJ, Arrizabalaga G.

Department of Microbiology, Molecular Biology and Biochemistry and Center for Reproductive Biology University of Idaho, Life Sciences South Room 142, Moscow, ID 83843, USA.

Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals. Successful propagation in an infected host by this obligate intracellular parasite depends on its ability to enter and exit host cells. Egress from the cell can be artificially induced by causing fluxes of calcium within the parasite with the use of calcium ionophores. While this ionophore-induced egress (IIE) has been characterized in detail, it is not known whether it mimics a normal physiological process of the parasite. This is underscored by the fact that mutants in IIE do not exhibit strong defects in any of the normal growth characteristics of the parasite in tissue culture. We have isolated and characterized a T. gondii mutant that along with a delay in IIE exhibits a severe defect in establishing a successful infection in vivo. In tissue culture this mutant displays normal ability to invade, divide within cells and convert into the latent encysted bradyzoite form. Nevertheless, mice infected with this mutant are less likely to die and carry less brain cysts than those infected with wild type parasites. Thus, our results suggest that normal response to calcium fluxes plays an important role during in vivo development of T. gondii.

PMID: 17643508 [PubMed - as supplied by publisher]

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Fluorine-containing aryloxyethyl thiocyanate derivatives: inhibitors of T. cruzi and Toxo proliferation

Bioorg Med Chem Lett. 2007 Jul 13; [Epub ahead of print]

Fluorine-containing aryloxyethyl thiocyanate derivatives are potent inhibitors of Trypanosoma cruzi and Toxoplasma gondii proliferation

Liñares GG, Gismondi S, Codesido NO, Moreno SN, Docampo R, Rodriguez JB.

Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina; Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.

As a part of our project aimed at developing new safe chemotherapeutic and chemoprophylactic agents against tropical diseases, fluorine-containing drugs structurally related to 4-phenoxyphenoxyethyl thiocyanate (1) were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas' disease), and Toxoplasma gondii, the etiological agent of toxoplasmosis. This thiocyanate derivative had previously proven to be an effective agent against T. cruzi proliferation. Fluorine-containing thiocyanate derivatives 2 and 3 were threefold more potent than our lead drug 1 against intracellular T. cruzi. The biological evaluation against T. gondii was also very promising. The IC(50) values corresponding to 2 and 3 were at the very low micromolar level against tachyzoites of T. gondii. Both of these drugs are interesting examples of effective antiparasitic agents that have outstanding potential not only as lead drugs but also to be used for further in vivo studies.

PMID: 17643987 [PubMed - as supplied by publisher]

A novel Toxo calcium-dependent protein kinase

Parasite. 2007 Jun;14(2):141-7.

A novel Toxoplasma gondii calcium-dependent protein kinase

Tzen M, Benarous R, Dupouy-Camet J, Roisin MP.

Institut Cochin, Département des Maladies infectieuses, Paris, France.

Toxoplasma gondii is an obligate intracellular parasite that infects all types of cells in humans. A family of calcium-dependent protein kinases (CDPKs), previously identified as important in the development of plants and protists, was recently shown to play a role in the infectivity of apicomplexans, and in motility and host cell invasion in particular. We report here the isolation of a new calcium-dependent protein kinase gene from the human toxoplasmosis parasite, Toxoplasma gondii. The gene consists of 12 exons. The encoded protein, TgCDPK4, consists of the four characteristic domains of members of the CDPK family and is most similar to PfCDPK2 from Plasmodium falciparum. We measured TgCDPK4 activity, induced by calcium influx, using a kinase assay. A calcium chelator (EGTA) inhibited this activity. These findings provide evidence of signal transduction involving members of the CDPK family in T. gondii.

PMID: 17645186 [PubMed - in process]

Tuesday, July 17, 2007

HDAC inhibitors and Toxo

J Parasitol. 2007 Jun;93(3):694-700

Scriptaid and suberoylanilide hydroxamic acid are histone deacetylase inhibitors with potent anti-Toxoplasma gondii activity in vitro

Strobl JS, Cassell M, Mitchell SM, Reilly CM, Lindsay DS.

Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Blacksburg, Virginia 24060, USA. jstrobl@vcom.vt.edu

Toxoplasma gondii is a well-recognized cause of disease in congenitally infected and immunocompromised individuals. Histone deacetylases (HDAC) comprise a family of enzymes that participate in the regulation of chromatin structure, gene expression, and cell signaling in eukaryotes. Toxoplasma gondii expresses a HDAC Class I enzyme homologous to human hdac3. Previous work showed that the histone deacetylase inhibitors (HDI) apicidin and valproic acid inhibit T. gondii infections in vitro. The present study compares the activity of hydroxamic-acid histone deacetylase inhibitors against the RH strain of T. gondii growing in HS68 human foreskin fibroblast cells. Nanomolar concentrations of suberoylanilide hydroxamic acid (SAHA), suberic bishydroxamic acid (SBHA), scriptaid, and trichostatin A (TSA) inhibited T. gondii tachyzoite proliferation. Scriptaid was the most potent hydroxamic acid inhibitor (IC50 = 39 nM). In comparison, the carboxylate histone deacetylase inhibitors sodium valproate, sodium butyrate, and 4-phenylbutyrate were less potent (IC50 range 1-5 mM). All of the inhibitors tested, except SBHA, completely protected the HS68 monolayers from T. gondii at concentrations 3-6 times greater than their respective IC50. In contrast, nicotinamide, an inhibitor of NADI-dependent Class III HDAC, had minimal activity against T. gondii in our in vitro assays. We conclude that the hydroxamic acid class of histone deacetylase inhibitors exhibit potent anti-T. gondii activity in vitro.

Characterization of a New Gene wx2 in Toxoplasma

Acta Biochim Biophys Sin (Shanghai). 2007 Jul;39(7):475-83.

Characterization of a New Gene wx2 in Toxoplasma gondii

Wu X, Zhang Q, Tan K, Xie R, Fan J, Shu H, Wang S.

Department of Parasitology, Xiangya Medical School, Central South University, Changsha 410078, China. hengpingshu@xysm.net, wshiping@hotmail.com.

Using hybridization techniques, we prepared the monoclonal antibody (Mab) 7C3-C3 against Toxoplasma gondii. The protection tests showed that the protein (Mab7C3-C3) inhibited the invasion and proliferation of T. gondii RH strain in HeLa cells. The passive transfer test indicated that the antibody significantly prolonged the survival time of the challenged mice. It was also shown that the antibody could be used for the detection of the circulating antigen of T. gondii. After immunoscreening the T. gondii tachyzoite cDNA library with Mab7C3-C3, a new gene wx2 of T. gondii was obtained. Immunofluorescence analysis showed that the WX2 protein was located on the membrane of the parasite. Nucleotide sequence comparison showed 28% identity to the calcium channel alpha-1E unit and shared with the surface antigen related sequence in some conservative residues. However, no match was found in protein databases. Therefore, it was an unknown gene in T. gondii encoding a functional protein on the membrane of T. gondii. Because it has been shown to have a partial protective effect against T. gondii infection and is released as a circulating antigen, it could be a candidate molecule for vaccine or a novel target for new drugs.

PMID: 17627323 [PubMed - in process]

Tuesday, July 10, 2007

Induction of egress by the potassium ionophore nigericin

Int J Parasitol. 2007 Jun 9; [Epub ahead of print]

Toxoplasma gondii: Induction of egress by the potassium ionophore nigericin

Fruth IA, Arrizabalaga G.

Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Life Sciences South Room 142, Moscow, ID 83843, USA.

The obligate intracellular parasite Toxoplasma gondii is an important pathogen of humans and animals. Some of the devastating consequences of toxoplasmosis are in part due to the lysis of the host cell during parasite egress. The process of egress is poorly understood and since it is asynchronous in tissue culture its study has been limited to those conditions that induce it, such as artificial permeabilisation of the host cell and induction of calcium fluxes with ionophores. Given that permeabilisation leads to egress by the activation of motility upon a drop in host cell potassium concentration, we investigated whether the ionophore nigericin, which selectively causes efflux of potassium from the cell without the need for permeabilisation, would cause egress. Nigericin effectively causes intracellular parasites to exit their host cell within 30min of treatment with the drug. Our results show that nigericin-induced egress depends on an efflux of potassium from the cell and requires phospholipase C function and parasite motility. This novel method of inducing and synchronising egress mimics the effect of artificial permeabilisation in all respects. Nevertheless, since the membrane remains intact during the treatment, in our nigericin-induced egress we are able to detect parasite-dependent permeabilisation of the host cell, a known step in induced egress. In addition, consistent with the model that loss of host cell potassium leads to egress through the activation of intraparasitic calcium fluxes, a previously isolated Toxoplasma mutant lacking a sodium hydrogen exchanger and defective in responding to calcium fluxes does not undergo nigericin-induced egress. Thus, the discovery that nigericin induces egress presents a novel assay that allows for the genetic and biochemical analysis of the signalling mechanisms that lead to the induction of motility and egress.

PMID: 17618633 [PubMed - as supplied by publisher]

Activation of TLR2 and TLR4 by Glycosylphosphatidylinositols Derived from Toxo

J Immunol. 2007 Jul 15;179(2):1129-37.

Activation of TLR2 and TLR4 by Glycosylphosphatidylinositols Derived from Toxoplasma gondii

Debierre-Grockiego F, Campos MA, Azzouz N, Schmidt J, Bieker U, Resende MG, Mansur DS, Weingart R, Schmidt RR, Golenbock DT, Gazzinelli RT, Schwarz RT.

Institut für Virologie, AG Parasitologie, Philipps University, Marburg, Germany;

GPIs isolated from Toxoplasma gondii, as well as a chemically synthesized GPI lacking the lipid moiety, activated a reporter gene in Chinese hamster ovary cells expressing TLR4, while the core glycan and lipid moieties cleaved from the GPIs activated both TLR4- and TLR2-expressing cells. MyD88, but not TLR2, TLR4, or CD14, is absolutely needed to trigger TNF-alpha production by macrophages exposed to T. gondii GPIs. Importantly, TNF-alpha response to GPIs was completely abrogated in macrophages from TLR2/4-double-deficient mice. MyD88(-/-) mice were more susceptible to death than wild-type (WT), TLR2(-/-), TLR4(-/-), TLR2/4(-/-), and CD14(-/-) mice infected with the ME-49 strain of T. gondii. The cyst number was higher in the brain of TLR2/4(-/-), but not TLR2(-/-), TLR4(-/-), and CD14(-/-), mice, as compared with WT mice. Upon infection with the ME-49 strain of T. gondii, we observed no decrease of IL-12 and IFN-gamma production in TLR2-, TLR4-, or CD14-deficient mice. Indeed, splenocytes from T. gondii-infected TLR2(-/-) and TLR2/4(-/-) mice produced more IFN-gamma than cells from WT mice in response to in vitro stimulation with parasite extracts enriched in GPI-linked surface proteins. Together, our results suggest that both TLR2 and TLR4 receptors may participate in the host defense against T. gondii infection through their activation by the GPIs and could work together with other MyD88-dependent receptors, like other TLRs or even IL-18R or IL-1R, to obtain an effective host response against T. gondii infection.

PMID: 17617606 [PubMed - in process]

Detection of toxoplasmic lesions by USPIO-enhanced magnetic resonance imaging

Magn Reson Imaging. 2007 Jul 3; [Epub ahead of print]

Detection of toxoplasmic lesions in mouse brain by USPIO-enhanced magnetic resonance imaging

Wei L, Zhou G, Li Z, He L, Gao M, Tan J, Lei H.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China; Graduate School, Chinese Academy of Sciences, Beijing 100039, PR China.

The objective of this study was to examine the feasibility of detecting toxoplasmic brain lesions in a mouse model of cerebral toxoplasmosis by ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI). Toxoplasmosis encephalitis was induced in Kunming mice by intracerebral injection of Toxoplasma gondii tachyzoites. T(2)- and T(2)*-weighted MRI was performed 1, 3, 4, 5 and 6 days after infection before USPIO injection; immediately after USPIO injection; and 24 h later. A comparison of USPIO enhancement and Gd-DTPA enhancement was made in three toxoplasmic mice 4 days after infection. Hematoxylin and eosin staining and Prussian blue staining were performed to detect inflammatory reactions and presence of iron in and around the toxoplasmic brain lesions. Nonenhanced T(2)-/T(2)*-weighted imaging detected few abnormalities in the brain up to 5 days. Most mice developed prominent hydrocephalus at 6 days. Gd-DTPA-enhanced imaging showed prominent enhancement of the cerebral ventricles but revealed only few space-occupying lesions in the parenchyma. USPIO-enhanced T(2)*-weighted imaging showed improved detection of toxoplasmic brain lesions that were invisible to nonenhanced T(2)-/T(2)*-weighted imaging and gadolinium-enhanced imaging. Most of the enhancing lesions showed nodular enhancement immediately after USPIO injection, some of which changed appearance 24 h later, having a ring enhancement at the outer rim. It can be concluded that USPIO enhancement of the toxoplasmic lesions may reflect blood-brain barrier impairment and/or inflammatory reactions associated with these lesions. USPIO-enhanced imaging may be used in combination with gadolinium-enhanced imaging to provide better characterization of toxoplasmic brain lesions and, potentially, improve the differential diagnosis of toxoplasmosis encephalitis.

PMID: 17614231 [PubMed - as supplied by publisher]

Tuesday, July 03, 2007

Building the Perfect Parasite: Cell Division in Apicomplexa

PLoS Pathog. 2007 Jun 29;3(6):e78 [Epub ahead of print]

Building the Perfect Parasite: Cell Division in Apicomplexa

Striepen B, Jordan CN, Reiff S, van Dooren GG.

Apicomplexans are pathogens responsible for malaria, toxoplasmosis, and crytposporidiosis in humans, and a wide range of livestock diseases. These unicellular eukaryotes are stealthy invaders, sheltering from the immune response in the cells of their hosts, while at the same time tapping into these cells as source of nutrients. The complexity and beauty of the structures formed during their intracellular development have made apicomplexans the darling of electron microscopists. Dramatic technological progress over the last decade has transformed apicomplexans into respectable genetic model organisms. Extensive genomic resources are now available for many apicomplexan species. At the same time, parasite transfection has enabled researchers to test the function of specific genes through reverse and forward genetic approaches with increasing sophistication. Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation. Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group? This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.

PMID: 17604449 [PubMed - as supplied by publisher]

Link between cryptogenic epilepsy and chronic toxoplasmosis infection

Seizure. 2007 Jun 27; [Epub ahead of print]

Meta-analysis of three case controlled studies and an ecological study into the link between cryptogenic epilepsy and chronic toxoplasmosis infection

Palmer BS.

Barts & The London, Queen Mary's School of Medicine & Dentistry, University of London, United Kingdom.

A meta-analysis was performed on three case controlled studies which examined the relationship between latent toxoplasmosis gondii infection in the immunocompetent host and cryptogenic epilepsy. Further comparison was also made by examining the seroprevalence of toxoplasmosis rates for 17 various countries, cities or regions against the prevalence rates for epilepsy in those regions. RESULTS: The results for the meta-analysis showed a log-odds ratio of 4.8 which approximates to a similar relative risk, (CI 2.6 to 7.8), with CI for all three studies being above 1. Seroprevalence rates for toxoplasmosis and prevalence rates of epilepsy showed a strong association (p<0.001). DISCUSSION: The prevalence of toxoplasmosis is an important factor in the prevalence of epilepsy with a probable link in the cryptogenic epilepsies. An area with a reduced burden of toxoplasmosis will also have a reduced burden of epilepsy. Neuropathophysiology findings from various studies show a common physical relationship of microglial nodule formation in Toxoplasma gondii infection and epilepsy. This analysis raises the possibility that one of the many causes of epilepsy may be an infectious agent, or that cryptogenic epilepsy may be a consequence of latent toxoplasmosis infection. This raises the possibility that public health measures to reduce toxoplasmosis infection may also result in a reduction in epilepsy.

PMID: 17604653 [PubMed - as supplied by publisher]