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artemisinin resistance

Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum

December 17, 2021 - 21:24 -- Open Access
Afolabi Owoloye, Michael Olufemi, Emmanuel T. Idowu and Kolapo M. Oyebola
Malaria Journal 2021 20:451, 2 December 2021

The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance.

NOT Open Access | Compensating P. falciparum artemisinin resistance

December 14, 2021 - 20:59 -- NOT Open Access
Platon L, Cao J, Ménard D
Cell Host Microbe. 2021 Dec 8;29(12):1732-1734

Amino acid deprivation from reduced hemoglobin degradation in Pfkelch13 artemisinin-resistant parasites reduces fitness.

NOT Open Access | The parasitophorous vacuole nutrient channel is critical for drug access in malaria parasites and modulates the artemisinin resistance fitness cost

December 7, 2021 - 21:27 -- NOT Open Access
Mesén-Ramírez P, Bergmann B, Spielmann T, et al.
Cell Host Microbe. 2021 Nov 30:S1931-3128(21)00508-4

Intraerythrocytic malaria parasites proliferate bounded by a parasitophorous vacuolar membrane (PVM). The PVM contains nutrient permeable channels (NPCs) conductive to small molecules, but their relevance for parasite growth for individual metabolites is largely untested. Here we show that growth-relevant levels of major carbon and energy sources pass through the NPCs.

Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria

November 20, 2021 - 14:24 -- Open Access
Moses Ikegbunam, Johnson A. Ojo, Kossiwa Kokou, Ugonna Morikwe, Chukwuemeka Nworu, Chibuzo Uba, Charles Esimone, Thirumalaisamy P. Velavan and Olusola Ojurongbe
Malaria Journal 2021 20:434, 10 November 2021

The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillance is necessary to make a definite conclusion on the emergence and pattern of possible resistance to ART.

NOT Open Access | Functional analyses of Plasmodium ferredoxin Asp97Tyr mutant related to artemisinin resistance of human malaria parasites

August 25, 2021 - 15:40 -- NOT Open Access
Kimata-Ariga Y, Morihisa R
J Biochem. 2021 Aug 20:mvab070

Mutation of Asp97Tyr in the C-terminal region of ferredoxin (PfFd) in the apicoplast of malaria parasites was recently reported to be strongly related to the parasite's resistance to the frontline antimalarial drug, artemisinin. We previously showed that the aromatic amino acid in the C-terminal region of PfFd is important for the interaction with its electron transfer partner, Fd-NADP+ reductase (PfFNR).

Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries

August 17, 2021 - 15:42 -- Open Access
Mathieu LC, Singh P, Monteiro WM, Magris M, Cox H, Lazrek Y, Melo GC, Marchesini P, Alexandre JSF, Alvarez AM, Demar M, Douine M, Ade MP, Lacerda MVG, Musset L
J Antimicrob Chemother. 2021 Aug 11:dkab264

The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations.

Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness

July 21, 2021 - 17:11 -- Open Access
Stokes BH, Dhingra SK, Fidock DA, et al.
Elife. 2021 Jul 19;10:e66277

The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failure across Southeast Asia. In Africa, K13-propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere.

NOT Open Access | Implicating extracellular vesicles in Plasmodium falciparum artemisinin resistance development

April 22, 2021 - 08:23 -- NOT Open Access
Tandoh KZ, Wilson MD, Quashie NB, Duah-Quashie NO
Traffic. 2021 Apr 15

Plasmodium falciparum malaria remains a disease of significant public health impact today. With the risk of emerging artemisinin resistance stalling malaria control efforts, the need to deepen our understanding of the parasite's biology is dire. Extracellular vesicles (EVs) are vital to the biology of P. falciparum and play a role in the pathogenesis of malaria.

Histone acetyltransferase PfGCN5 regulates stress responsive and artemisinin resistance related genes in Plasmodium falciparum

January 21, 2021 - 15:26 -- Open Access
Rawat M, Kanyal A, Sahasrabudhe A, Vembar SS, Lopez-Rubio JJ, Karmodiya K
Sci Rep. 2021 Jan 13;11(1):852

Plasmodium falciparum has evolved resistance to almost all front-line drugs including artemisinin, which threatens malaria control and elimination strategies. Oxidative stress and protein damage responses have emerged as key players in the generation of artemisinin resistance. In this study, we show that PfGCN5, a histone acetyltransferase, binds to the stress-responsive genes in a poised state and regulates their expression under stress conditions.

Plasmodium berghei K13 Mutations Mediate In Vivo Artemisinin Resistance That Is Reversed by Proteasome Inhibition

November 11, 2020 - 14:33 -- Open Access
Simwela NV, Stokes BH, Aghabi D, Bogyo M, Fidock DA, Waters AP
mBio. 2020 Nov 10;11(6):e02312-20

The recent emergence of Plasmodium falciparum parasite resistance to the first line antimalarial drug artemisinin is of particular concern. Artemisinin resistance is primarily driven by mutations in the P. falciparum K13 protein, which enhance survival of early ring-stage parasites treated with the artemisinin active metabolite dihydroartemisinin in vitro and associate with delayed parasite clearance in vivo However, association of K13 mutations with in vivo artemisinin resistance has been problematic due to the absence of a tractable model.


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