Mining thePlasmodiumgenome database to define organellar function: what does the apicoplast do?

Abstract

Apicomplexan species constitute a diverse group of parasitic protozoa, which are responsible for a wide range of diseases in many organisms. Despite differences in the diseases they cause, these parasites share an underlying biology, from the genetic controls used to differentiate through the complex parasite life cycle, to the basic biochemical pathways employed for intracellular survival, to the distinctive cell biology necessary for host cell attachment and invasion. Different parasites lend themselves to the study of different aspects of parasite biology: Eimeria for biochemical studies, Toxoplasma for molecular genetic and cell biological investigation, etc. The Plasmodium falciparum Genome Project contributes the first large-scale genomic sequence for an apicomplexan parasite. The Plasmodium Genome Database (http://PlasmoDB. org) has been designed to permit individual investigators to ask their own questions, even prior to formal release of the reference P. falciparum genome sequence. As a case in point, PlasmoDB has been exploited to identify metabolic pathways associated with the apicomplexan plastid, or 'apicoplast'-an essential organelle derived by secondary endosymbiosis of an alga, and retention of the algal plastid.

Peroxiredoxins in Parasites

“…Many also contain a chloroplast-derived apicoplast (216), which, for those that have it, is essential and is the site of 612 GRETES ET AL. The genome sequencing for this organism is in progress but is not publicly available.…”

Apicoplast genome of the coccidian Eimeria tenella

“…Recently, a number of nuclearencoded apicoplast proteins were identified from T. gondii and P. falciparum, including several Type II fatty acid synthetic enzymes (i.e., fabH, fabACP, fabZ, etc.) (Waller et al, 1998;Surolia and Surolia, 2001;Roos et al, 2002;Wilson, 2002) and isoprenoid pathway (Jomaa et al, 1999). These enzymes appeared to be essential to the Apicomplexa since thiolactomycin and triclosan (inhibitors for Type II ketoacyl synthase and enoyl reductase, respectively) could block the growth of P. falciparum in vitro (Waller et al, 1998;Surolia and Surolia, 2001).…”

Biosynthetic Pathways of Plastid-Derived Organelles as Potential Drug Targets Against Parasitic Apicomplexa

“…Haem biosynthesis might be another potentially interesting target since at least some of the enzymes with putative apicoplast targeting domains have been found on the nuclear genome of P. falciparum [34,37]. One of it, δ-aminolevulinic acid dehydratase (ALAD), has been shown to be functional in E. coli and possess an N-terminal extension, possibly acting as a targeting signal to the apicoplast [124].…”

“…Owing to these characteristic features a preliminary map of putatively apicoplast-localized proteins had been assembled, using available genome data from P. falciparum. According to this estimation more than 150 nuclear-encoded proteins were estimated to be transported to the plastid [37]. With the recent completion of the genome sequence of P. falciparum this number has now increased to 551 ( [44], see also http://www.nature.com/nature/malaria and http://plasmodb.org for more information).…”

“…It seems that almost all extant Apicomplexa have retained the plastid, although for C. parvum there is some evidence that points to the loss of the apicoplast genome in this organism [33]. For recent and excellent in-depth reviews on the biology of the apicoplast see [31,[34][35][36][37].…”