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• W4386538855 abstract "<ns4:p><ns4:bold>Background:</ns4:bold> Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ) are the essential long-acting partner drugs in the artemisinin-based combination therapies (ACTs) treatment regimens globally. The recent report on the emergence of artemisinin-resistant parasites portends an imminent failure of the partner drug in clearing the high residual parasite densities. Understanding the resistance mechanisms to partner drugs remains critical for tracking resistant parasites. Cysteine desulfurase IscS (<ns4:italic>nfs1</ns4:italic>), one of the proteins involved in the iron-sulfur (FeS) biogenesis pathway, has been implicated in mediating malaria parasite drug resistance. </ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Using the rodent malaria parasites <ns4:italic>Plasmodium berghei </ns4:italic>ANKA in mice, we assessed whether the <ns4:italic>nfs1</ns4:italic> gene is associated with LM, PQ, and AQ resistance. We first verified the stability of the LM, PQ, and AQ-resistant parasites in the standard 4-Day Suppressive Test. By means of PCR and sequencing analysis, we probed for single nucleotide polymorphisms (SNPs) in the <ns4:italic>nfs1</ns4:italic> gene. Using qPCR, we then measured the expression of the <ns4:italic>nfs1 </ns4:italic>gene in resistant parasites relative to the drug-sensitive parent parasites. </ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> Our analyses of <ns4:italic>nfs1</ns4:italic> reveal a non-synonymous Gln142Arg mutation in the LM and PQ-resistant parasites. This mutation was not detected in the AQ-resistant parasites. The mRNA quantification of the <ns4:italic>nfs1</ns4:italic> gene reveals differential expression in both LM and PQ-resistant parasites. Conversely, <ns4:italic>nfs1 </ns4:italic>expression remained unchanged in the AQ-resistant parasites.</ns4:p><ns4:p> <ns4:bold>Conclusion:</ns4:bold> Our data suggest that LM and PQ selection pressure induces nonsynonymous mutation and differential expression of the <ns4:italic>nfs1 </ns4:italic>gene in <ns4:italic>Plasmodium berghei</ns4:italic>. Collectively, these findings provide a premise for investigating LM and PQ resistance mechanisms in both <ns4:italic>P. berghei</ns4:italic> and <ns4:italic>P. falciparum</ns4:italic>.</ns4:p>" @default.
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• W4386538855 date "2023-09-08" @default.
• W4386538855 modified "2023-10-18" @default.
• W4386538855 title "Lumefantrine pressure selects nonsynonymous mutation in cysteine desulfurase IscS gene in the rodent malaria parasite Plasmodium berghei ANKA" @default.
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• W4386538855 doi "https://doi.org/10.12688/openresafrica.13457.3" @default.
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