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Ca(2+) channels regulate many crucial processes within cells and their abnormal activity can be damaging to cell survival, suggesting that they might represent attractive therapeutic targets in pathogenic organisms. Parasitic diseases such as malaria, leishmaniasis, trypanosomiasis and schistosomiasis are responsible for millions of deaths each year worldwide. The genomes of many pathogenic parasites have recently been sequenced, opening the way for rational design of targeted therapies. We analyzed genomes of pathogenic protozoan parasites as well as the genome of Schistosoma mansoni, and show the existence within them of genes encoding homologues of mammalian intracellular Ca(2+) release channels: inositol 1,4,5-trisphosphate receptors (IP(3)Rs), ryanodine receptors (RyRs), two-pore Ca(2+) channels (TPCs) and intracellular transient receptor potential (Trp) channels. The genomes of Trypanosoma, Leishmania and S. mansoni parasites encode IP(3)R/RyR and Trp channel homologues, and that of S. mansoni additionally encodes a TPC homologue. In contrast, apicomplexan parasites lack genes encoding IP(3)R/RyR homologues and possess only genes encoding TPC and Trp channel homologues (Toxoplasma gondii) or Trp channel homologues alone. The genomes of parasites also encode homologues of mammalian Ca(2+) influx channels, including voltage-gated Ca(2+) channels and plasma membrane Trp channels. The genome of S. mansoni also encodes Orai Ca(2+) channel and STIM Ca(2+) sensor homologues, suggesting that store-operated Ca(2+) entry may occur in this parasite. Many anti-parasitic agents alter parasite Ca(2+) homeostasis and some are known modulators of mammalian Ca(2+) channels, suggesting that parasite Ca(2+) channel homologues might be the targets of some current anti-parasitic drugs. Differences between human and parasite Ca(2+) channels suggest that pathogen-specific targeting of these channels may be an attractive therapeutic prospect.
Pubmed ID: 22022573
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Database of genomes at various stages of completion, from early access to partial genomes with automatic annotation through to complete genomes with extensive manual curation. Its primary goals are: 1) to provide reliable access to the latest sequence data and annotation/curation for the whole range of organisms sequenced by the Pathogen group, and 2) to develop the website and other tools to aid the community in accessing and obtaining the maximum value from these data.
View all literature mentionsEuPathDB integrates numerous database resources and multiple data types. The phylum Apicomplexa comprises veterinary and medically important parasitic protozoa including human pathogenic species of genera Cryptosporidium, Plasmodium and Toxoplasma. ApiDB serves not only as database but unifies access to three major existing individual organism databases, PlasmoDB.org, ToxoDB.org and CryptoDB.org, and integrates these databases with data available from additional sources. Through ApiDB site, users may pose queries and search all available apicomplexan data and tools, or they may visit individual component organism databases. EuPathDB Bioinformatics Resource Center for Biodefense and Emerging/Re-emerging Infectious Diseases is a portal for accessing genomic-scale datasets associated with eukaryotic pathogens.
View all literature mentionsThe directing and coordinating authority responsible for public health within the United Nations system. The WHO Regional Office for Europe (WHO/Europe) is one of the six regional offices around the world. It serves the WHO European Region, which comprises 53 countries from the Atlantic to the Pacific oceans. WHO/Europe collaborates with a range of public health stakeholders in the Region and globally, to ensure that coordinated action is taken to develop and implement efficient health policies and to strengthen health systems. WHO/Europe is made up of public health, scientific, and technical experts.
View all literature mentionsA free, simple to use web service dedicated to reconstructing and analysing phylogenetic relationships between molecular sequences. Phylogeny.fr runs and connects various bioinformatics programs to reconstruct a robust phylogenetic tree from a set of sequences.
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