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Background: The tumor-like growth of the metacestode larvae of the tapeworm E. multilocularis causes human alveolar echinococcosis, a severe disease mainly affecting the liver. The germinative cells, a population of adult stem cells, are crucial for the larval growth and development of the parasite within the hosts. Maintenance of the germinative cell pools relies on their abilities of extensive proliferation and self-renewal, which requires accurate control of the cell division cycle. Targeting regulators of the cell division progression may impair germinative cell populations, leading to impeded parasite growth. Methodology/Principal findings: In this study, we describe the characterization of EmAURKA and EmAURKB, which display significant similarity to the members of Aurora kinases that are essential mitotic kinases and play key roles in cell division. Our data suggest that EmAURKA and EmAURKB are actively expressed in the germinative cells of E. multilocularis. Treatment with low concentrations of MLN8237, a dual inhibitor of Aurora A and B, resulted in chromosomal defects in the germinative cells during mitosis, while higher concentrations of MLN8237 caused a failure in cytokinesis of the germinative cells, leading to multinucleated cells. Inhibition of the activities of Aurora kinases eventually resulted in depletion of the germinative cell populations in E. multilocularis, which in turn caused larval growth inhibition of the parasite. Conclusions/Significance: Our data demonstrate the vital roles of Aurora kinases in the regulation of mitotic progression and maintenance of the germinative cells in E. multilocularis, and suggest Aurora kinases as promising druggable targets for the development of novel chemotherapeutics against human alveolar echinococcosis. [ABSTRACT FROM AUTHOR]

The cloned enolase gene of Angiostrongylus cantonensis ( AcEno) comprised 1,667 bp and encoded a peptide with 434 amino acid residues which lacked of a signal peptide but contained a transmembrane region, indicating that AcEno tends to be a structural component (intracellular or membrane protein). The real-time PCR revealed a meaningful difference in the expression level of AcEno in varied development stages. By immunolocalization, native AcEno was detected mainly in the cytoplasm in most tissues, such as parietal muscle, genital tracts, nerve ring, and alimentary canal where the energy consumption is high, but not as expected on the cuticle and hypodermis layer of the nematode. This suggests that the AcEno may be involved in a host of other biological functions, rather than a receptor of plasminogen or a component of excretory-secretory antigen. In addition, AcEno expressed alike in the nucleus, indicating that AcEno also involved in regulating the continuous growth and development of A. cantonensis in hosts. Despite of living in the vasculature at a certain stage of life cycle, AcEno was not localized in the outer surface of L3 and adults, indicating that A. cantonensis may have other virulence and immune evasion mechanisms. [ABSTRACT FROM AUTHOR]

The expressed sequence tags (ESTs) of Angiostrongylus cantonensis were analyzed in an attempt to gain further insight into its genomic expression patterns. A total of 1,277 ESTs of A. cantonensis were randomly downloaded from NCBI databank. ESTs were analyzed and annotated using Blastx. The result showed that there were 60 ESTs had no match to any of the proteins and gene sequences in the published databases, and 695 ESTs score more than 80. According to the function, the identified 695 ESTs could be grouped into 13 categories related to metabolism, cellular development, immune evasion, host–parasite interactions, and so on. Among them, 65 (9.4%) were proteases and protease inhibitors, represented 19 potential proteases and protease inhibitors genes; 42 (6.0%) were allergens or antigens, represented 15 potential antigens/allergens genes. SignalP analysis was applied to the 19 putative proteases and protease inhibitors and the 15 antigens/allergens protein sequences to identify the potential signal peptides and anchors. The result demonstrated that there were ten putative proteins had N-terminal signal peptides and three had signal anchors, these putative excretory/secretory proteins might be the products of potential parasitism genes which played an important role in the adaptation of A. cantonensis to a parasitism life. These parasitism genes and proteins identified are expected to become potential targets for future research on anti- A. cantonensis drugs; moreover, the resulting genetic information is useful in elucidating the mechanisms of parasitism of A. cantonensis. [ABSTRACT FROM AUTHOR]