Drug Resist Updat. 2000 Oct;3(5):283-287.

Atovaquone resistance in malaria parasites.

Source

Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, USA

Abstract

Atovaquone is a broad-spectrum antiparasitic agent active against malaria, Pneumocystis carinii pneumonia, toxoplasmosis and babesiosis. When used as a single agent, resistance to atovaquone arose rapidly in falciparum malaria, requiring the development of a new antimalarial drug combination of atovaquone and proguanil. Recent laboratory investigations have provided insights into the mode of atovaquone action, and identified the molecular basis for the resistance development. Mutations within a catalytic domain of the cytochrome bc(1)complex present within the parasite mitochondrial inner membrane were shown to be responsible for atovaquone resistance. Here, we review these studies and propose a mechanism by which atovaquone resistance may arise quickly in malaria parasites. Copyright 2000 Harcourt Publishers Ltd.

PMID:: 11498396; [PubMed - as supplied by publisher]

LinkOut - more resources

Full Text Sources

Libraries

LinkOut Holdings

Supplemental Content

Related citations

Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. [Mol Microbiol. 1999]
Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites.
Srivastava IK, Morrisey JM, Darrouzet E, Daldal F, Vaidya AB. Mol Microbiol. 1999 Aug; 33(4):704-11.
Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. [Antimicrob Agents Chemother. 2000]
Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site.
Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q. Antimicrob Agents Chemother. 2000 Aug; 44(8):2100-8.
Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil. [Malar J. 2008]
Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil.
Sutherland CJ, Laundy M, Price N, Burke M, Fivelman QL, Pasvol G, Klein JL, Chiodini PL. Malar J. 2008 Nov 20; 7:240. Epub 2008 Nov 20.
Review Atovaquone/proguanil: a review of its use for the prophylaxis of Plasmodium falciparum malaria. [Drugs. 2003]
Review Atovaquone/proguanil: a review of its use for the prophylaxis of Plasmodium falciparum malaria.
McKeage K, Scott L. Drugs. 2003; 63(6):597-623.
Review Modeling the molecular basis of atovaquone resistance in parasites and pathogenic fungi. [Trends Parasitol. 2007]
Review Modeling the molecular basis of atovaquone resistance in parasites and pathogenic fungi.
Kessl JJ, Meshnick SR, Trumpower BL. Trends Parasitol. 2007 Oct; 23(10):494-501. Epub 2007 Sep 7.

See reviews... See all...

Cited by 6 PubMed Central articles

Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene. [Malar J. 2010]
Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene.
Afonso A, Neto Z, Castro H, Lopes D, Alves AC, Tomás AM, Rosário VD. Malar J. 2010 May 21; 9:135. Epub 2010 May 21.
A drug-selected Plasmodium falciparum lacking the need for conventional electron transport. [Mol Biochem Parasitol. 2008]
A drug-selected Plasmodium falciparum lacking the need for conventional electron transport.
Smilkstein MJ, Forquer I, Kanazawa A, Kelly JX, Winter RW, Hinrichs DJ, Kramer DM, Riscoe MK. Mol Biochem Parasitol. 2008 May; 159(1):64-8. Epub 2008 Jan 19.
Sequence analysis of Plasmodium falciparum cytochrome b in multiple geographic sites. [Malar J. 2007]
Sequence analysis of Plasmodium falciparum cytochrome b in multiple geographic sites.
Ekala MT, Khim N, Legrand E, Randrianarivelojosia M, Jambou R, Fandeur T, Menard D, Assi SB, Henry MC, Rogier C, et al. Malar J. 2007 Dec 17; 6:164. Epub 2007 Dec 17.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Atovaquone resistance in malaria parasites.
Atovaquone resistance in malaria parasites.
Drug Resist Updat. 2000 Oct ;3(5):283-287.

PubMed
A randomized, double-blind, comparative trial of a new oral combination of artem...
A randomized, double-blind, comparative trial of a new oral combination of artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute Plasmodium falciparum malaria in Thailand.
Am J Trop Med Hyg. 1999 Feb ;60(2):238-43.

PubMed
Epidemiology of drug-resistant malaria.
Epidemiology of drug-resistant malaria.
Lancet Infect Dis. 2002 Apr ;2(4):209-18.

PubMed
Bionomics and systematics of the oriental Anopheles sundaicus complex in relatio...
Bionomics and systematics of the oriental Anopheles sundaicus complex in relation to malaria transmission and vector control.
Am J Trop Med Hyg. 2004 Oct ;71(4):518-24.

PubMed
Estimating the needs for artesunate-based combination therapy for malaria case-m...
Estimating the needs for artesunate-based combination therapy for malaria case-management in Africa.
Trends Parasitol. 2003 Aug ;19(8):363-9.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to:

Atovaquone resistance in malaria parasites.

Source

Abstract

LinkOut - more resources

Full Text Sources

Libraries

Supplemental Content

Related citations

Cited by 6 PubMed Central articles

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information