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PubMed1991

Activity of water extracts of Albizzia anthelmintica and A. lebbek barks against experimental Hymenolepis diminuta infection in rats.

The aqueous extract of Albizzia anthelmintica bark at 10-150 g/kg orally showed no toxicity and high anthelmintic activity (68-100%) against experimental Hymenolepis diminuta infection in albino rats. The water extract from A. lebbek bark at 10-100 g/kg orally was less effective against the cestode and was toxic to rats at the highest dose tested (150 g/kg).

Animals↗
PubMed1993

Distribution and immunochemical characteristics of neuropeptide F (NPF) (Moniezia expansa) - immunoreactivity in Proteocephalus pollanicola (Cestoda: Proteocephalidea).

1. Using immunocytochemical techniques and confocal scanning laser microscopy, the proteocephalidean cestode, Proteocephalus pollanicola from Lough Neagh pollan (Coregomus autumnalis) was examined for the presence of the native platyhelminth neuropeptide, neuropeptide F (NPF). 2. An antiserum specific for whole-molecule NPF (1-39) (Moniezia expansa) did not immunostain nerve processes in P. pollanicola. A C-terminally-directed NPF (30-39) (M. expansa) antiserum immunostained nerve fibres and cell bodies of both the central and peripheral nervous systems, including innervation associated with the female reproductive system. 3. The pattern of immunoreactivity was identical to that obtained using antisera to the C-terminal region of mammalian NPY-superfamily peptides and the invertebrate neuropeptide, FMRFamide. 4. Under radioimmunoassay conditions, only the C-terminally-directed NPF antiserum cross-reacted with the P. pollanicola peptide and detected 58.74 ng/g wet weight of NPF-1 R in extracts of the worm. 5. Chromatographic characterisation of P. pollanicola NPF-immunoreactivity indicated an apparent molecular weight of 4400-4700 Da, similar to that of NPF (M. expansa). 6. Further analytical HPLC characterisation identified two molecular forms of P. pallanicoda NPF-immunoreactivity, both of which had different retention times from those of NPF (M. expansa) and NPF (Artioposthia triangulata). 7. These data suggest that P. pollanicola possesses a neuropeptide which is homologous in its C-terminal region to NPF (M. expansa) but differs in its mid- to N-terminal region.

Amino Acid Sequence↗
PubMed2005

Tribendimidine: a promising, safe and broad-spectrum anthelmintic agent from China.

We review, for the first time, a 20-year Chinese story of research and development pertaining to tribendimidine, a promising anthelmintic agent that is safe and exhibits a broad spectrum of activity. Tribendimidine was first synthesized at the National Institute of Parasitic Diseases in Shanghai in the mid 1980s. In laboratory studies, tribendimidine showed high efficacy against Nippostrongylus braziliensis in rats, Necator americanus in hamsters, Ancylostoma caninum and Toxocara canis in dogs, and Syphacia mesocriceti in mice. Activity was also found against several species of cestodes in chicken. In clinical trials, a single oral dose of 400 mg tribendimidine, administered to patients infected only with N. americanus, or with N. americanus and Ancylostoma duodenalis, resulted in cure rates of 85.7% (132/154) and 89.8% (53/59), respectively. In comparison, a single oral dose of 400 mg albendazole resulted in significantly lower cure rates, namely 65.5% (91/139; chi(2) = 16.47, P < 0.001) and 71.7% (43/60; chi(2) = 6.29, P = 0.012), respectively. Single oral doses of tribendimidine (300 mg) and albendazole (400mg) were equally effective against Ascaris lumbricoides infections; cure rates were 96.0% (97/101) and 98.1% (101/103), respectively. In 5-14-year-old children with an Enterobius vermicularis infection, treated with a single oral dose of 200 mg tribendimidine, a cure rate of 81.6% (93/114) was observed. Tribendimidine was well-tolerated as only mild and transient side effects were observed. It would be of great public health significance if these findings are confirmed in other epidemiological settings, as more than one-quarter of the world population is currently affected by intestinal nematodes, with only very few drugs currently available on the market.

Animals↗
PubMed2006

Development and sexual maturation of Echinococcus granulosus adult worms in the alternative definitive host, Mongolian gerbil (Meriones unguiculatus).

In the present study for the first time an alternative definitive host model has been established for the complete development of Echinococcus granulosus in Meriones unguiculatus (Mongolian gerbils) up to shelled eggs production, as happened in the natural host. Animals treated with methylprednisolone acetate were orally inoculated with approximately 3000 protoscoleces and the development of parasites in the small intestine observed up to 46 days post-infection (p.i.). The cestodes survive, strobilate, mature sexually and complete their development in the intestine up to production of shelled embryonated eggs containing fully formed six-hooked oncospheres, similarly to the natural canid host (stage 7 by Smyth). Shelled eggs are first observed in the rodent/E. granulosus model at 44 days p.i. Somatic growth in gerbils appears to follow a similar trend to dogs, length increasing to over 3mm at 44 days p.i., while, compared to the natural host, organogenesis is observed only to progress at a slower rate in the early developmental stages. Parasite burden was found to vary among non-inbred animals and developmental stages of worms recovered from the same animal differed widely. Worm localisation follows the pattern observed in the natural host, the parasites appearing for the most part distributed in the proximal third of the small intestine. The development of alternative definitive hosts may facilitate research in this field, overcoming legislative impediments that restrict the use of dogs for experimental purposes.

Animals↗
PubMed2004

Muscular myosin isoforms of Taenia solium (Cestoda).

Type II myosin, the primary component of the thick filament of muscle fibers, is organized as a dimeric high molecular weight protein, and is composed of a pair of heavy chains (MHC) and two pairs of light chains. Myosin II transforms ATP energy into mechanical force. All type II myosins are conserved proteins but they have two variable regions that are located in different places of the molecule. Myosin molecules are encoded by a multigene family and many isoforms are generated. The expression of myosins depends on the developmental stage and on the type and degree of contractile activity and tissue, therefore several myosin isoforms are found in the same organism. Here we describe the use of different techniques that allowed demonstrating the presence of isoforms of the heavy chain type II myosin of Taenia solium cysticerci (larvae) and tapeworms (adults), a cestode parasite of importance in public health in many developing countries. Myosin was purified and used in comparative proteolytic fragmentation, ATPase activity, detection of antigenic differences and electrophoretic separation. The results obtained showed biochemical and immunochemical differences among cysticerci and tapeworms, and demonstrate the presence of myosin isoforms in T. solium that are probably associated to physiological requirements of each developmental stage.

Adenosine Triphosphatases↗
PubMed2006

Advances in liver echinococcosis: diagnosis and treatment.

Echinococcosis or hydatid cyst disease is a zoonosis caused by the larval cestode Echinococcus granulosus. It consists of a parasitic tapeworm disease affecting mainly liver. Nevertheless, the disease might well spread to more unusual sites such as lungs and brain. The definitive diagnosis of liver echinococcosis requires a combination of imaging, serologic, and immunologic studies. Despite the fact that a number of scolecoidal agents have been developed against liver hydatid disease, the cornerstone of the definitive treatment remains surgery. Both the classic surgical techniques and the recently developed minimally invasive and laparoscopic methods target the eradication of the disease by simultaneously avoiding perioperative spillage and dissemination or recurrence of echinococcosis. The present article constitutes a review of the biology of the parasite as well as the epidemiology, diagnosis, and therapeutic options of the liver hydatid disease.

Algorithms↗
PubMedDate not supplied

Mesocestoides corti: a LIM-homeobox gene upregulated during strobilar development.

To understand the molecular processes regulating morphological changes during cestode life histories we focused on homeodomain (HD) proteins, a family of transcription factors essential for pattern formation during development. In this study we report the isolation of the partial sequence of MvLim, a LIM-HD gene of Mesocestoides corti. Other members of this gene family, characterized in Drosophila melanogaster, Caenorhabditis elegans and vertebrates contribute to cell fate determination of various neuronal subtypes. Phylogenetic analyses showed that MvLim clusters with members of the LIN-11 group and that platyhelminths have at least two different LIM-HD genes. By real time PCR we determined that MvLim expression is 20-fold greater in segmented worms than in tetrathyridia. The enhancement of MvLim expression during strobilation could be associated to changes in the innervation pattern occurring in proglottids development.

Amino Acid Sequence↗
PubMed2005

Taenia saginata: differential diagnosis of human taeniasis by polymerase chain reaction-restriction fragment length polymorphism assay.

Speciation of Taenia in human stool is important because of their different clinical and epidemiological features. DNA analysis has recently become possible which overcomes the problems of differentiating human taeniid cestodes morphologically. In the present study, we evaluated PCR coupled to restriction fragment length polymorphism to differentiate Taenia solium from Taenia saginata eggs present in fecal samples from naturally infected patients. A different DraI-RFLP pattern: a two-band pattern (421 and 100 bp) for T. saginata and a three-band pattern (234, 188, and 99 bp) for T. solium was observed allowing the two species to be separated. The lower detection limit of the PCR-RFLP using a non-infected fecal sample prepared with a given number of T. saginata eggs was 34 eggs in 2 g stool sediment. The 521 bp mtDNA fragment was detected in 8 out of 12 Taenia sp. carriers (66.6%). Of these, three showed a T. solium pattern and five a T. saginata pattern.

Animals↗
PubMed2003

Identification, molecular characterization and expression of the gene encoding the epidermal growth factor receptor orthologue from the fox-tapeworm Echinococcus multilocularis.

Receptor tyrosine kinases (RTKs) are crucially involved in the development of metazoan organisms and possible mediators of cell-cell communication that occurs between eukaryotic parasites and hosts. We have now cloned and characterized the complete complementary DNA (cDNA) molecule encoding a novel receptor tyrosine kinase, EmER, of the human parasite Echinococcus multilocularis. EmER shared significant amino acid sequence homologies with members of the epidermal growth factor (EGF) receptor family of different phylogenetic origin, exhibited a domain structure which is typical for this group of membrane receptors and contained all catalytically important residues at the corresponding positions. Highest homologies were detected between EmER and a previously identified receptor kinase, SER, from the parasitic trematode Schistosoma mansoni. The EmER encoding gene, emer, spans a chromosomal region of 39 kb and is composed of 23 exons. Structural comparisons indicated that emer and the EGF receptor encoding genes from mammals derive from a common ancestor. DNA/DNA hybridization experiments demonstrated that emer is present as a single copy locus in the parasite. Transcriptional analyses on in vitro cultivated parasite larvae revealed that emer is expressed in both the metacestode and the protoscolex stage, although about 10-fold higher transcription levels were detectable for the protoscolex. Northern blot experiments further indicated that emer is expressed as a single 5.2-kb transcript in parasitic larvae during an infection of the intermediate host. These results suggest an involvement of EmER in echinococcal differentiation processes towards the protoscolex stage during natural infections and provide, for the first time, structural information on an epidermal growth factor receptor-like kinase from a cestode.

Amino Acid Sequence↗
PubMed2004

Pharmacological characterisation of neuropeptide F (NPF)-induced effects on the motility of Mesocestoides corti (syn. Mesocestoides vogae) larvae.

Neuropeptide F is the most abundant neuropeptide in parasitic flatworms and is analogous to vertebrate neuropeptide Y. This paper examines the effects of neuropeptide F on tetrathyridia of the cestode Mesocestoides vogae and provides preliminary data on the signalling mechanisms employed. Neuropeptide F (>/=10 microM) had profound excitatory effects on larval motility in vitro. The effects were insensitive to high concentrations (1 mM) of the anaesthetic procaine hydrochloride suggesting extraneuronal sites of action. Neuropeptide F activity was not significantly blocked by a FMRFamide-related peptide analog (GNFFRdFamide) that was found to inhibit GNFFRFamide-induced excitation indicating the occurrence of distinct neuropeptide F and FMRFamide-related peptide receptors. Larval treatment with guanosine 5'-O-(2-thiodiphosphate) trilithium salt prior to the addition of neuropeptide F completely abolished the excitatory effects indicating the involvement of G-proteins and a G-protein coupled receptor in neuropeptide F activity. Addition of guanosine 5'-O-(2-thiodiphosphate) following neuropeptide F had limited inhibitory effects consistent with the activation of a signalling cascade by the neuropeptide. With respect to Ca(2+) involvement in neuropeptide F-induced excitation of M. vogae larvae, the L-type Ca(2+)-channel blockers verapamil and nifedipine both abolished neuropeptide F activity as did high Mg(+) concentrations and drugs which blocked sarcoplasmic reticulum Ca(2+)-activated Ca(2+)-channels (ryanodine) and sarcoplasmic reticulum Ca(2+) pumps (cyclopiazonic acid). Therefore, both extracellular and intracellular Ca(2+) is important for neuropeptide F excitation in M. vogae. With respect to second messengers, the protein kinase C inhibitor chelerythrine chloride and the adenylate cyclase inhibitor MDL-2330A both abolished neuropeptide F-induced excitation. The involvement of a signalling pathway that involves protein kinase C was further supported by the fact that phorbol-12-myristate-13-acetate, known to directly activate protein kinase C, had direct excitatory effects on larval motility. Although neuropeptide F is structurally analogous to neuropeptide Y, its mode-of-action in flatworms appears quite distinct from the common signalling mechanism seen in vertebrates.

Animals↗
PubMed2004

A PCR system for detection of species and genotypes of the Echinococcus granulosus-complex, with reference to the epidemiological situation in eastern Africa.

We describe the development of a specific and sensitive PCR/semi-nested PCR system for the rapid diagnosis of Echinococcus granulosus genotype G1, E. granulosus genotype G6/7, and Echinococcus ortleppi (G5). Diagnosis of G1 and the group G5/6/7 is performed by a simple PCR, while discrimination between E. ortleppi (G5) and G6/7 involves a subsequent semi-nested PCR step. The target sequence for amplification is part of the mitochondrial 12S rRNA gene. Specificity of the PCRs was 100% when evaluated with isolates of 16 species of cestodes, including Echinococcus multilocularis, Echinococcus equinus, E. ortleppi and three strains of E. granulosus (G1, G6 and G7). Sensitivity threshold was 0.25pg of DNA. This new approach was compared with published protocols of restriction fragment length polymorphism-PCR and sequencing of mitochondrial cytochrome c oxidase subunit 1 and NADH dehydrogenase 1 genes using Echinococcus isolates of human, sheep, goat, camel, cattle and pig origin from Kenya and Sudan. Additionally, two internal DNA probes were developed, one hybridising only with G1, the other with G5, G6 and G7 amplification products. Preliminary epidemiological results obtained with this PCR approach include the detection of a camel strain (G6) infection for the first time in a human patient from eastern Africa, and the first reports of E. ortleppi (G5) in livestock from Kenya and the Sudan.

Animals↗
PubMed2005

Australian ecosystems, capricious food chains and parasitic consequences for people.

Characteristic Australian ecosystems or environments contain numerous food chains some of which may become capriciously side-tracked or appropriated by humans, with parasitic consequences for people in Australia and overseas. Twelve of 13 arboviruses affecting humans are of wildlife origin and all are transmitted by mosquitoes. In this case, transmission is thus associated with aquatic environments, many artificial. Zoonotic trematode (brachylaimiasis) and cestode (rodentoleposis) infections have been reported from semi-arid environments. Scabies and angiostrongylosis are associated with work, recreational and home environments. Four species of Rickettsia endemic in wildlife are acquired by humans from fleas, mites and ticks in bush and semi-urban environments. The enigmatic and life-threatening muspiceoid nematode, Haycocknema perplexum, is known from people associated with the natural environment in Tasmania; whether it comes from vertebrates, invertebrates, plants, soil or water is unknown. Food chains occurring in a range of Australian ecosystems and environments, some associated with feeding arthropods, others with accidental ingestion of invertebrates, may result in human exposure and infection. A range of organisms normally occurring in wildlife, domestic animals or the environment may be involved in causing human disease.

Animals↗
PubMed2005

An unusual blood sequestering tapeworm (Sanguilevator yearsleyi n. gen., n. sp.) from Borneo with description of Cathetocephalus resendezi n. sp. from Mexico and molecular support for the recognition of the order Cathetocephalidea (Platyhelminthes: Eucestoda).

Sanguilevator yearsleyi n. gen., n. sp. and Cathetocephalus resendezi n. sp. are described from the Broadfin shark, Lamiopsis temmincki, in Malaysian Borneo and Carcharhinus leucas in Mexico, respectively. The new genus is unusual in its possession of internal chambers and channels in its scolex that appear to house extensive quantities of host white and red blood cells, respectively. Histology reveals an extremely intimate association between host tissue and the surface of the apical pad of the scolex. Positive staining with periodic acid-Schiff of the surface of the pad of the scolex and the linings of the chambers and channels suggests that an adhesive substance may be produced in these regions. However, explanations for how and why host blood cells come to reside within the scolex remain elusive. Cathetocephalus resendezi n. sp. is distinctive in the form of the papillae in the papillate band of the scolex and also in the inconspicuous nature of the rugose base of the scolex. Scanning electron microscopy of both new taxa as well as Cathetocephalus thatcheri, Cathetocephalus australis and an undescribed species of Cathetocephalus collected from Carcharhinus amboinensis in Australia, suggests that the papillae surrounding the pad of the scolex are of significant taxonomic utility in distinguishing among species in these groups. Parsimony and Bayesian analyses of sequence data (766 bases of 18S rDNA and 405 bases of 28S rDNA) generated from ethanol preserved specimens of C. thatcheri and S. yearsleyi, when compared with equivalent data available for 40 cestode species in GenBank, resulted in trees that support previous propositions that Cathetocephalus should be placed in the order Cathetocephalidea. The results suggest that Sanguilevator should also be considered to belong to this order.

Animals↗
PubMed2005

Role of the programmed Death-1 pathway in the suppressive activity of alternatively activated macrophages in experimental cysticercosis.

We characterised a population of macrophages potentially involved in the immunoregulation induced by experimental cysticercosis. Following Taenia crassiceps infection, macrophages recruited in the peritoneal cavity were isolated and co-cultured at different ratios with T cells from naïve mice previously stimulated with anti-CD3/CD28 antibodies; these macrophages inhibited naïve T cell proliferation. This suppressive effect was Interleukin (IL)-10, Interferon-gamma (IFN-gamma), and nitric oxide (NO) independent. In contrast, macrophage-T cell contact was necessary to maintain anergy of T cells. Reverse transcriptase-PCR analysis of these macrophages showed higher transcripts of IL-10, chitinases Fizz1 and Ym1, and arginase-1 compared with naïve macrophages; by contrast, IL-12p40, and inducible nitric oxide synthase (iNOS) transcripts were undetected, whereas C-C chemokine ligand 5 (CCL5) was unchanged. Analysis of the membrane molecules expressed on Taenia-induced macrophages showed an up-regulation of several markers, mainly programmed death ligand 1 (PD-L1) and PD-L2. Blockade of PD-L1, PD-L2 or their receptor PD-1, but not of another marker, eliminated their ability to inhibit T-cell proliferation. Parallel experiments using ovalbumin (OVA)-peptide as a model antigen displayed similar results. Additionally, the same mechanism appears to be functional in splenocytes of T. crassiceps-infected mice given that blockade of PD-1, PD-L1 or PD-L2 re-established their ability to proliferate in response to parasite antigens. Moreover, Taenia-induced macrophages were able to suppress a mixed lymphocyte reaction in a PD-1-dependent manner. Thus, cestode infections induce macrophages alternatively activated with strong suppressive activity involving the PD-1/PD-L's pathway.

Animals↗
PubMed2005

Human behaviour and the epidemiology of parasitic zoonoses.

The behaviour of Homo sapiens has a pivotal role to play in the macro and microepidemiology of emerging or re-emerging parasitic zoonoses. Changing demographics and the concomitant alterations to the environment, climate, technology, land use and changes in human behavior, converge to favour the emergence and spread of parasitic zoonoses. The recent unprecedented movements of people, their animals and their parasites around the world, introduce and mix genes, cultural preferences, customs, and behavioral patterns. The increasing proclivity for eating meat, fish, crabs, shrimp, molluscs raw, undercooked, smoked, pickled or dried facilitates a number of protozoan (Toxoplasma), trematode (Fasciola sp., Paragonimus spp., Clonorchis sp., Opisthorchis spp., Heterophyes sp., Metagonimus sp., Echinostoma spp., Nanophyetus sp.) cestode (Taenia spp, Diphyllobothrum sp.) and nematode (Trichinella spp., Capillaria spp., Gnathostoma spp., Anisakis sp., Parastrongylus spp.) caused zoonoses. The increasing world population and the inability to keep pace with the provision of adequate sanitation and clean, safe drinking water, has led to an increased importance of waterborne zoonoses, such as those caused by Giardia, Cryptosporidium and Toxoplasma. Our close relationship with and the numerous uses to which we put companion animals and their ubiquitous distribution has resulted in dogs and cats unwitting participation in sharing over 60 parasite species including: Giardia, Cryptosporidium, Toxoplasma, most foodborne trematode species, Diphyllobothrum, Echinococcus spp., Ancylostoma and Toxocara. Changing human behaviour through education, to encourage the proper cooking of food, which may have cultural and social significance, will remain as challenging as controlling stray and feral pet populations, improving hygiene levels and the provision of safe drinking water and the proper use of sanctuary facilities. Long pre-patent periods and the normally insidious sub-clinical nature of most zoonoses makes advice requiring behavioural change for their control a difficult task. Our clearer understanding of the heterogeneity of susceptibility to infection, the complex genetic variations of people and parasite species and the development of molecular epidemiological tools is shedding more light on transmission routes and the spectrum of disease that is observed. Improved and new serological, molecular and imaging diagnostic tests and the development of broad spectrum chemotherapeutic agents has led to the attenuation of morbidity and mortality due to parasitic zoonoses in economically advantaged regions. Such advancements, in partnership with supportive behavioural change, has the potential for a sustainable global reduction in the burden of ill health due to parasitic zoonoses. Whether this will materialise is a challenge for us all.

Animals↗
PubMed2005

Fish-borne parasitic zoonoses: status and issues.

The fish-borne parasitic zoonoses have been limited for the most part to populations living in low- and middle-income countries, but the geographical limits and populations at risk are expanding because of growing international markets, improved transportation systems, and demographic changes such as population movements. While many in developed countries will recognize meat-borne zoonoses such as trichinellosis and cysticercosis, far fewer are acquainted with the fish-borne parasitic zoonoses which are mostly helminthic diseases caused by trematodes, cestodes and nematodes. Yet these zoonoses are responsible for large numbers of human infections around the world. The list of potential fish-borne parasitic zoonoses is quite large. However, in this review, emphasis has been placed on liver fluke diseases such as clonorchiasis, opisthorchiasis and metorchiasis, as well as on intestinal trematodiasis (the heterophyids and echinostomes), anisakiasis (due to Anisakis simplex larvae), and diphyllobothriasis. The life cycles, distributions, epidemiology, clinical aspects, and, importantly, the research needed for improved risk assessments, clinical management and prevention and control of these important parasitic diseases are reviewed.

Animals↗
PubMed2006

Variation in infection parameters among populations within parasite species: intrinsic properties versus local factors.

Within any parasite species, variation among populations in standard infection parameters (prevalence, intensity and abundance) is an accepted fact. The proportion of hosts infected and the mean number of parasites per host are not fixed values across the entire geographic range of any parasite species. The question is whether this inter-population variation occurs within a narrow, species-specific range and is thus driven mainly by the biological features of the parasite, or whether it is substantial and unpredictable, leaving population parameters at the mercy of local conditions. Here, the repeatability of estimates of prevalence, intensity and abundance of infection was assessed across populations of the same parasite species, for 77 metazoan parasite species of Canadian freshwater fishes. Overall, parameter values from different populations of the same parasite species were more similar to each other and more different from those of other species, than expected by chance alone. Much of the variation in parameter values in the dataset was associated with differences between parasite species, rather than with differences among populations within species. This was particularly true for intensity and abundance of infection; in contrast, prevalence values, while somewhat repeatable among populations of the same species, still showed considerable variation. Among the higher taxa investigated (monogeneans, trematodes, cestodes, nematodes, acanthocephalans, copepods), there was no evidence that species of one taxon display intrinsically greater variation in population parameters than species of other taxa. Overall, the results suggest that intensity and abundance of infection are real species characters, though somewhat variable. This conclusion supports the view that the biological features of parasite species can potentially override local environmental conditions in driving parasite population dynamics.

Animals↗
PubMed2006

Characterisation of EmMPK1, an ERK-like MAP kinase from Echinococcus multilocularis which is activated in response to human epidermal growth factor.

Mitogen-activated protein (MAP) kinases are key regulators of cellular signalling systems that mediate responses to a wide variety of extracellular stimuli and should also play a central role in developmental mechanisms of parasitic helminths. Until now, however, no MAP kinase orthologue has been characterised in a member of this parasite group. Here, we report the identification and characterisation of such a molecule, EmMPK1, from the human parasitic cestode Echinococcus multilocularis. Using a degenerative PCR approach, we isolated and completely sequenced the 1.2kb cDNA for EmMPK1 which displays significant homologies to known MAP kinases of different phylogenetic origin. EmMPK1 contains all amino acid residues which are characteristic for MAP kinases, including a conserved TEY motif which identifies the protein as a member of the ERK subfamily of MAP kinases. The corresponding gene, emmpk1 (6.9 kb), was characterised and contained 10 introns. Southern blot hybridisation studies showed that emmpk1 is present as single copy locus in E. multilocularis. Using RT-PCR analyses we demonstrated that emmpk1 is expressed in form of three different transcripts which derive from alternative splice acceptor site utilisation at intron 9. Using EmMPK1-specific antibodies in Western blot studies and immunohistochemistry, we detected the Echinococcus protein and its phosphorylated form in the larval stages metacestode and protoscolex during in vitro cultivation and during an infection of the intermediate host. EmMPK1, immunoprecipitated from Echinococcus lysate, was able to phosphorylate myelin basic protein in activity assays, indicating that it is a functionally active MAP kinase. Finally, we also show that phosphorylation of EmMPK1 is specifically induced in vitro-cultivated E. multilocularis metacestode vesicles in response to exogenous host serum and upon addition of human epidermal growth factor. These data indicate that the E. multilocularis metacestode is able to sense epidermal growth factor from the host which results in an activation of the parasite's MAP kinase cascade.

Alternative Splicing↗