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

• Published in: International journal for parasitology 2014-04, Vol.44 (5), p.285-289
• Main Authors: Goodman, Christopher D., Mollard, Vanessa, Louie, Theola, Holloway, Georgina A., Watson, Keith G., McFadden, Geoffrey I.
• Format: Article
• Language: English
• Subjects: Acetyl Co-A carboxylase; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Apicoplast; Apicoplasts - enzymology; Cyclohexanones - metabolism; Enzyme Inhibitors - metabolism; Fatty acid biosynthesis; Gene Deletion; Gene Expression Profiling; Herbicides; Herbicides - metabolism; Malaria; Plasmodium falciparum; Plasmodium falciparum - enzymology
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2014.01.007

[Display omitted] •Plasmodium falciparum acetyl-CoA carboxylase (PfACC) localises to the apicoplast.•PfACC is not essential for in vitro blood stage growth of P. falciparum.•ACC inhibiting herbicides kill parasites but not by targeting PfACC. 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.