Journal article

Targeting NAD( ) Metabolism in the Human Malaria Parasite Plasmodium falciparum

Jessica K O'Hara, Lewis J Kerwin, Simon A Cobbold, Jonathan Tai, Thomas A Bedell, Paul J Reider, Manuel Llinas

PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2014

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of ..

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University of Melbourne Researchers

Grants

Awarded by Burrough's Wellcome fund (Investigators in Pathogenesis of Infectious Disease Award for Research), an NIH Director's New Innovator Award


Awarded by Center for Quantitative Biology


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH


Funding Acknowledgements

This work was funded through generous support from the Burrough's Wellcome fund (Investigators in Pathogenesis of Infectious Disease Award for Research), an NIH Director's New Innovator Award (1DP2OD001315-01), and with support from the Center for Quantitative Biology (P50 GM071508). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.