Cool new paper from
Joe Derisi's lab:
PLoS Biology: Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum. by Ellen Yeh and Joseph L. DeRisi. doi: 10.1371/journal.pbio.1001138
In it they use some experimental techniques to try and track down the elusive function of the apicoplast in Plasmodium falciparum, the causative agent of malaria. The apicoplast is an organelle that is evolutionarily derived from chloroplasts (and thus derived originally from cyanobacteria). Due to it's cyanobacterial origins many have thought that it might serve as a good target for drugs to try and kill
Plasmodium species because in theory such drugs if specific should not have significant detrimental effects on hosts like humans due to our lack of known important cyanobacterial associates.
Here is their abstract:
Plasmodium spp parasites harbor an unusual plastid organelle called the apicoplast. Due to its prokaryotic origin and essential function, the apicoplast is a key target for development of new anti-malarials. Over 500 proteins are predicted to localize to this organelle and several prokaryotic biochemical pathways have been annotated, yet the essential role of the apicoplast during human infection remains a mystery. Previous work showed that treatment with fosmidomycin, an inhibitor of non-mevalonate isoprenoid precursor biosynthesis in the apicoplast, inhibits the growth of blood-stage P. falciparum. Herein, we demonstrate that fosmidomycin inhibition can be chemically rescued by supplementation with isopentenyl pyrophosphate (IPP), the pathway product. Surprisingly, IPP supplementation also completely reverses death following treatment with antibiotics that cause loss of the apicoplast. We show that antibiotic-treated parasites rescued with IPP over multiple cycles specifically lose their apicoplast genome and fail to process or localize organelle proteins, rendering them functionally apicoplast-minus. Despite the loss of this essential organelle, these apicoplast-minus auxotrophs can be grown indefinitely in asexual blood stage culture but are entirely dependent on exogenous IPP for survival. These findings indicate that isoprenoid precursor biosynthesis is the only essential function of the apicoplast during blood-stage growth. Moreover, apicoplast-minus P. falciparum strains will be a powerful tool for further investigation of apicoplast biology as well as drug and vaccine development.
