Apicoplast acetyl Co-A carboxylase of the human malaria parasite is not targeted by cyclohexanedione herbicides

作者:Goodman Christopher D; Mollard Vanessa; Louie Theola; Holloway Georgina A; Watson Keith G; McFadden Geoffrey I*
来源:International Journal for Parasitology, 2014, 44(5): 285-289.
DOI:10.1016/j.ijpara.2014.01.007

摘要

Malaria parasites retain a relict plastid (apicoplast) from a photosynthetic ancestor. The apicoplast is a useful drug target but the specificity of compounds believed to target apicoplast fatty acid biosynthesis has become uncertain, as this pathway is not essential in blood stages of the parasite. Herbicides that inhibit the plastid acetyl Coenzyme A (Co-A) carboxylase of plants also kill Plasmodium falciparum in vitro, but their mode of action remains undefined. We characterised the gene for acetyl Co-A carboxylase in P. falciparum. The P. falciparum acetyl-CoA carboxylase gene product is expressed in blood stage parasites and accumulates in the apicoplast. Ablation of the gene did not render parasites insensitive to herbicides, suggesting that these compounds are acting off-target in blood stages of P. falciparum. (C) 2014 The Authors. Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc. This is an open access article under the CC BY-NG-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).