Literature DB >> 25331708

Atovaquone tolerance in Plasmodium falciparum parasites selected for high-level resistance to a dihydroorotate dehydrogenase inhibitor.

Jennifer L Guler1, John White1, Margaret A Phillips2, Pradipsinh K Rathod3.   

Abstract

Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genetic cross talk" between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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Year:  2014        PMID： 25331708      PMCID： PMC4291421          DOI： 10.1128/AAC.02347-14

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


  33 in total

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Authors:  Eli Schwartz; Shay Bujanover; Kevin C Kain
Journal:  Clin Infect Dis       Date:  2003-07-18       Impact factor: 9.079

2.  Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80).

Authors:  M Fry; M Pudney
Journal:  Biochem Pharmacol       Date:  1992-04-01       Impact factor: 5.858

3.  Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site.

Authors:  M Korsinczky; N Chen; B Kotecka; A Saul; K Rieckmann; Q Cheng
Journal:  Antimicrob Agents Chemother       Date:  2000-08       Impact factor: 5.191

4.  Prevalence of Plasmodium falciparum cytochrome b gene mutations in isolates imported from Africa, and implications for atovaquone resistance.

Authors:  A Berry; A Senescau; J Lelièvre; F Benoit-Vical; R Fabre; B Marchou; J F Magnaval
Journal:  Trans R Soc Trop Med Hyg       Date:  2006-05-11       Impact factor: 2.184

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Journal:  Eur J Biochem       Date:  2000-04

6.  Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite.

Authors:  I K Srivastava; H Rottenberg; A B Vaidya
Journal:  J Biol Chem       Date:  1997-02-14       Impact factor: 5.157

7.  Frequency of drug resistance in Plasmodium falciparum: a nonsynergistic combination of 5-fluoroorotate and atovaquone suppresses in vitro resistance.

Authors:  S Gassis; P K Rathod
Journal:  Antimicrob Agents Chemother       Date:  1996-04       Impact factor: 5.191

8.  Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria.

Authors:  Quinton L Fivelman; Geoffrey A Butcher; Ipemida S Adagu; David C Warhurst; Geoffrey Pasvol
Journal:  Malar J       Date:  2002-02-08       Impact factor: 2.979

9.  Clonal viability measurements on Plasmodium falciparum to assess in vitro schizonticidal activity of leupeptin, chloroquine, and 5-fluoroorotate.

Authors:  R D Young; P K Rathod
Journal:  Antimicrob Agents Chemother       Date:  1993-05       Impact factor: 5.191

10.  A mechanism for the synergistic antimalarial action of atovaquone and proguanil.

Authors:  I K Srivastava; A B Vaidya
Journal:  Antimicrob Agents Chemother       Date:  1999-06       Impact factor: 5.191
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3.  Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series.

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Journal:  J Med Chem       Date:  2021-04-20       Impact factor: 7.446

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

Authors:  Heather J Painter; Joanne M Morrisey; Michael W Mather; Lindsey M Orchard; Cuyler Luck; Martin J Smilkstein; Michael K Riscoe; Akhil B Vaidya; Manuel Llinás
Journal:  Antimicrob Agents Chemother       Date:  2021-02-17       Impact factor: 5.938

5.  Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.

Authors:  Benjamin K Dickerman; Brendan Elsworth; Simon A Cobbold; Catherine Q Nie; Malcolm J McConville; Brendan S Crabb; Paul R Gilson
Journal:  Sci Rep       Date:  2016-11-22       Impact factor: 4.379

6.  Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites.

Authors:  Dorjbal Dorjsuren; Richard T Eastman; Anton Simeonov; David A Fidock; Kathryn J Wicht; Daniel Jansen; Daniel C Talley; Benjamin A Sigmon; Alexey V Zakharov; Norma Roncal; Andrew T Girvin; Yevgeniya Antonova-Koch; Paul M Will; Pranav Shah; Hongmao Sun; Carleen Klumpp-Thomas; Sachel Mok; Tomas Yeo; Stephan Meister; Juan Jose Marugan; Leila S Ross; Xin Xu; David J Maloney; Ajit Jadhav; Bryan T Mott; Richard J Sciotti; Elizabeth A Winzeler; Norman C Waters; Robert F Campbell; Wenwei Huang
Journal:  Sci Rep       Date:  2021-01-22       Impact factor: 4.379

7.  Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.

Authors:  Maureen A Carey; Jason A Papin; Jennifer L Guler
Journal:  BMC Genomics       Date:  2017-07-19       Impact factor: 3.969

8.  Identification and Mechanistic Understanding of Dihydroorotate Dehydrogenase Point Mutations in Plasmodium falciparum that Confer in Vitro Resistance to the Clinical Candidate DSM265.

Authors:  John White; Satish K Dhingra; Xiaoyi Deng; Farah El Mazouni; Marcus C S Lee; Gustavo A Afanador; Aloysus Lawong; Diana R Tomchick; Caroline L Ng; Jade Bath; Pradipsinh K Rathod; David A Fidock; Margaret A Phillips
Journal:  ACS Infect Dis       Date:  2018-11-13       Impact factor: 5.084
  8 in total

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