Targeting the apicoplast in malaria

Biddau, M. and Sheiner, L. (2019) Targeting the apicoplast in malaria. Biochemical Society Transactions, 47(4), pp. 973-983. (doi: 10.1042/BST20170563) (PMID:31383817)

Abstract

Malaria continues to be one of the leading causes of human mortality in the world, and the therapies available are insufficient for eradication. Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Apicomplexan parasites, including the Plasmodium spp., are descendants of photosynthetic algae, and therefore they possess an essential plastid organelle, named the apicoplast. Since humans and animals have no plastids, the apicoplast is an attractive target for drug development. Indeed, after its discovery, the apicoplast was found to host the target pathways of some known antimalarial drugs, which motivated efforts for further research into its biological functions and biogenesis. Initially, many apicoplast inhibitions were found to result in ‘delayed death’, whereby parasite killing is seen only at the end of one invasion-egress cycle. This slow action is not in line with the current standard for antimalarials, which seeded scepticism about the potential of compounds targeting apicoplast functions as good candidates for drug development. Intriguingly, recent evidence of apicoplast inhibitors causing rapid killing could put this organelle back in the spotlight. We provide an overview of drugs known to inhibit apicoplast pathways, alongside recent findings in apicoplast biology that may provide new avenues for drug development.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Biddau, Dr Marco and Sheiner, Professor Lilach
• Authors: Biddau, M., and Sheiner, L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Biochemical Society Transactions
• Publisher: Portland Press
• ISSN: 0300-5127
• ISSN (Online): 1470-8752
• Published Online: 05 August 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Biochemical Society Transactions 47(4):973–983
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher