Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in Plasmodium falciparum-Reference-Cited by-同舟云学术

Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in Plasmodium falciparum

Published:2021-02-17 Issue:3 Volume:65 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Painter Heather J.¹^ORCID,Morrisey Joanne M.²,Mather Michael W.²^ORCID,Orchard Lindsey M.¹^ORCID,Luck Cuyler¹^ORCID,Smilkstein Martin J.³^ORCID,Riscoe Michael K.³^ORCID,Vaidya Akhil B.²^ORCID,Llinás Manuel¹⁴^ORCID

Affiliation:

1. Department of Biochemistry and Molecular Biology, Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, USA

2. Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

3. Medical Research Service, Department of Veterans Affairs Medical Center, Portland, Oregon, USA

4. Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania, USA

Abstract

The continued emergence of drug-resistant Plasmodium falciparum parasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt) bc 1 complex, which is an essential component of the mitochondrial electron transport chain (mtETC) required for ubiquinone recycling and mitochondrially localized dihydroorotate dehydrogenase (DHODH) critical for de novo pyrimidine synthesis.

Funder

Veterans Administration Research Career Scientist Award

HHS | National Institutes of Health

HHS | U.S. Food and Drug Administration

Bill and Melinda Gates Foundation

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.02143-20

Reference56 articles.