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kelch13

Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)

May 25, 2020 - 08:56 -- Open Access
Author(s): 
Romaric Nzoumbou-Boko, Chris-Boris Gildas Panté-Wockama, Didier Ménard, et al.
Reference: 
Malaria Journal 2020 19:191, 24 May 2020

Over the last decade, artemisinin-based combination therapy (ACT) has contributed substantially to the decrease in malaria-related morbidity and mortality. The emergence of Plasmodium falciparum parasites resistant to artemisinin derivatives in Southeast Asia and the risk of their spread or of local emergence in sub-Saharan Africa are a major threat to public health. This study thus set out to estimate the proportion of P. falciparum isolates, with Pfkelch13 gene mutations associated with artemisinin resistance previously detected in Southeast Asia.

Amplicon deep sequencing of kelch13 in Plasmodium falciparum isolates from Senegal

March 31, 2020 - 16:01 -- Open Access
Author(s): 
Amy Gaye, Mouhamad Sy, Daouda Ndiaye, et al.
Reference: 
Malaria Journal 2020 19:134, 30 March 2020

In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether–lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency.

Decreased K13 Abundance Reduces Hemoglobin Catabolism and Proteotoxic Stress, Underpinning Artemisinin Resistance

December 2, 2019 - 14:43 -- Open Access
Author(s): 
Yang T, Yeoh LM, Cobbold SA, et al.
Reference: 
Cell Rep. 2019 Nov 26;29(9):2917-2928.e5

Increased tolerance of Plasmodium falciparum to front-line artemisinin antimalarials (ARTs) is associated with mutations in Kelch13 (K13), although the precise role of K13 remains unclear. Here, we show that K13 mutations result in decreased expression of this protein, while mislocalization of K13 mimics resistance-conferring mutations, pinpointing partial loss of function of K13 as the relevant molecular event.

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