BackgroundProtein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear.Methodology/Principal FindingsWe employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade.ConclusionsWe conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.
SUMMARYPlasmodium knowlesi has risen in importance as a zoonotic parasite that
has been causing regular episodes of malaria throughout South East Asia. The P.
knowlesi genome sequence generated in 2008 highlighted and confirmed many
similarities and differences in Plasmodium species, including a global
view of several multigene families, such as the large SICAvar multigene
family encoding the variant antigens known as the schizont-infected cell agglutination
proteins. However, repetitive DNA sequences are the bane of any genome project, and this
and other Plasmodium genome projects have not been immune to the gaps,
rearrangements and other pitfalls created by these genomic features. Today, long-read
PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based
on the use of these technologies, we present a highly refined de novo P.
knowlesi genome sequence of the Pk1(A+) clone. This sequence and annotation,
referred to as the ‘MaHPIC Pk genome sequence’, includes manual annotation of the
SICAvar gene family with 136 full-length members categorized as type I
or II. This sequence provides a framework that will permit a better understanding of the
SICAvar repertoire, selective pressures acting on this gene family and
mechanisms of antigenic variation in this species and other pathogens.
Plasmodium coatneyi is a protozoan parasite species that causes simian malaria and is an excellent model for studying disease caused by the human malaria parasite, P. falciparum. Here we report the complete (nontelomeric) genome sequence of P. coatneyi Hackeri generated by the application of only Pacific Biosciences RS II (PacBio RS II) single-molecule real-time (SMRT) high-resolution sequence technology and assembly using the Hierarchical Genome Assembly Process (HGAP). This is the first Plasmodium genome sequence reported to use only PacBio technology. This approach has proven to be superior to short-read only approaches for this species.
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