Host biotin is required for liver stage development in malaria parasites

Teegan A. Dellibovi-Ragheb, Hugo Jhun, Christopher D. Goodman, Maroya S. Walters, Daniel R.T. Ragheb, Krista A. Matthews, Krithika Rajaram, Satish Mishra, Geoffrey I. McFadden, Photini Sinnis, Sean T. Prigge

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin.

Original languageEnglish (US)
Pages (from-to)E2604-E2613
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number11
DOIs
Publication statusPublished - Jan 1 2018

    Fingerprint

Keywords

  • Acetyl-CoA carboxylase
  • Apicoplast
  • Biotin ligase
  • Holocarboxylase synthetase
  • Plasmodium

ASJC Scopus subject areas

  • General

Cite this