TITLE:
Molecular Investigation of Genetic Signatures of Selection in Plasmodium falciparum Actin-Binding Protein Coronin, Cysteine Desulfurase, and Plasmepsin 2 Gene in Mbita Field Isolates, Western Kenya
AUTHORS:
Houdou Diarra, Edward E. Makhulu, Peter O. Odhiambo, Robinson M. Irekwa, Johnson Kinyua, Jeremy K. Herren, Victor A. Mobegi
KEYWORDS:
Plasmodium falciparum, Mutations, Artemisinin, Lumefantrine, Piperaquine
JOURNAL NAME:
Open Journal of Genetics,
Vol.11 No.4,
December
22,
2021
ABSTRACT: Background: Plasmodium falciparum (Pf) resistance to antimalarial drugs is
a major impediment to malaria control. The Pf.Kelch 13 (PfK13) gene has been largely reported to be associated with
artemisinin resistance. However, recent studies have shown artemisinin
resistance without Kech13 mutations
suggesting the implication of others genes in artemisinin resistance. In this
current study, we focused on mutations in Pf.actin-binding
protein coronin, Pf.cysteine desulfurase
and Pf.plasmepsin 2 gene, three
putative candidates recently were reported to be involved
in artemisinin, lumefantrine and piperaquine resistance respectively. Method: Archived blood samples previously collected from asymptomatic school
children from December 2016 to October 2018 were used in this study. Genomic
DNA was extracted using ISOLATE II Genomic DNA kit. After PCR
amplification, amplicons were purified and sequenced by capillary sequencing.
Reads were analyzed for the identification of point mutations previously
reported to be involved in drug selection. Results: Mutations R100K, and
G50E involved in reduced artemisinin susceptibility were detected in Pfcoronin. From 2016/17 to 2018 the
allele 100k increased frequency (11.2%); while 50E was only observed in 2018
time point reaching 11.1%. Lumefantrine
selection marker K65, in codon (K65Q) was observed at 14.2% in Pfcysteine desulfurase, and the mutant’
allele 65Q gradually increased frequency from 28.5% in 2016/17 to 57.1% in
2018. Pf.plasmepsin 2 was the less polymorphic gene. Several other polymorphism codons
and single nucleotide variants were detected. Conclusion: The findings
indicate the presence of mutations associated with reduced artemisinin
susceptibility and lumefantrine selection marker. Therefore, the results call
for continuous monitoring of molecular makers in Mbita parasites.