The Key Glycolytic Enzyme Phosphofructokinase Is Involved in Resistance to Antiplasmodial Glycosides

Author:

Fisher Gillian M.1,Cobbold Simon A.2,Jezewski Andrew3,Carpenter Emma F.4ORCID,Arnold Megan1,Cowell Annie N.5,Tjhin Erick T.6ORCID,Saliba Kevin J.6ORCID,Skinner-Adams Tina S.1ORCID,Lee Marcus C. S.4,Odom John Audrey7ORCID,Winzeler Elizabeth A.5,McConville Malcolm J.2ORCID,Poulsen Sally-Ann1,Andrews Katherine T.1ORCID

Affiliation:

1. Griffith Institute for Drug Discovery, Griffith University, Queensland, Australia

2. University of Melbourne, Victoria, Australia

3. Washington School of Medicine, St. Louis, Missouri, USA

4. Wellcome Sanger Institute, Cambridge, United Kingdom

5. University of California, San Diego, San Diego, California, USA

6. The Australian National University, Canberra, Australia

7. Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Abstract

Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue, causing 405,000 deaths and 228 million cases in 2018. Understanding key metabolic processes in malaria parasites is critical to the development of new drugs to combat this major infectious disease. The Plasmodium glycolytic pathway is essential to the malaria parasite, providing energy for growth and replication and supplying important biomolecules for other essential Plasmodium anabolic pathways. Despite this overreliance on glycolysis, no current drugs target glycolysis, and there is a paucity of information on critical glycolysis targets. Our work addresses this unmet need, providing new mechanistic insights into this key pathway.

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference57 articles.

1. WHO. 2019. World malaria report, 2019. World Health Organization, Geneva, Switzerland.

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4. PlasmoDB: a functional genomic database for malaria parasites

5. Plant-like phosphofructokinase from Plasmodium falciparum belongs to a novel class of ATP-dependent enzymes

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