Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Fun

Question

Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum

dx.doi.org/10.1371/journal.pbio.1001138

Paper Critique#2 Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum dx.dol.org/10.1371/journalpbio 1001138 Due Wednesday, 28 March, by 5pm 1- Describe the most interesting finding of the paper, in your opinion, and explain why you found it interesting. (3 points, 4-5 sentences minimum) 2) Would IPP be able to rescue liver stage Plasmodium parasite viability in the presence of apicoplast destroying antibiotics? (2 points; 3-4 sentences minimum. 1pt. for trying and following instructions, 1 pt. for a correct answer)

Explanation / Answer

Chemical Rescue of Malaria parasites LAcking an Apicoplast :

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.

- Treatment with fosmidomycin, an inhibitor of non-mevalonate isoprenoid precursor biosynthesis in the apicoplast, inhibits the growth of blood-stage P. falciparum.

- 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.

- 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.

Related Questions

Navigate

• Browse (All)
• Browse C
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.