Format

Send to

Choose Destination
Cell Rep. 2019 Jan 8;26(2):356-363.e4. doi: 10.1016/j.celrep.2018.12.062.

Plasmodium Para-Aminobenzoate Synthesis and Salvage Resolve Avoidance of Folate Competition and Adaptation to Host Diet.

Author information

1
Department of Molecular Parasitology, Institute of Biology, Humboldt University, 10115 Berlin, Germany; Parasitology Unit, Max Planck Institute of Infection Biology, 10117 Berlin, Germany. Electronic address: joachim.michael.matz@hu-berlin.de.
2
Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, 14476 Potsdam-Golm, Germany; Nara Institute of Science and Technology, Graduate School of Biological Sciences, Plant Secondary Metabolism, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan.
3
University of Kentucky College of Pharmacy, Lexington, KY, USA.
4
Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, 14476 Potsdam-Golm, Germany.
5
Department of Molecular Parasitology, Institute of Biology, Humboldt University, 10115 Berlin, Germany; Parasitology Unit, Max Planck Institute of Infection Biology, 10117 Berlin, Germany.

Abstract

Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by the mammalian host is restricted and that only pABA, rather than fully formed folate, is taken up efficiently. This adaptation, which readily adjusts infection to highly variable pABA levels in the mammalian diet, is specific to blood stages and may have evolved to avoid folate competition between the parasite and its host.

KEYWORDS:

ADCL; ADCS; Plasmodium; aminodeoxychorismate lyase; aminodeoxychorismate synthase; folate; malaria; milk; pABA; para-aminobenzoic acid

PMID:
30625318
DOI:
10.1016/j.celrep.2018.12.062
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center