Investigation of genetic diversity of Plasmodium knowlesi kelch13-propeller region  in Sabah, Malaysia

Jennifer Kui Ling Chee; Eric Tzyy Jiann Chong; Ping-chin Lee

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Investigation of genetic diversity of Plasmodium knowlesi kelch13-propeller region in Sabah, Malaysia

Author: Jennifer Kui Ling Chee ¹ ; Eric Tzyy Jiann Chong ² ; Ping-Chin Lee ^{1
,

2}
Author Information

1. Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.&
2. Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia.
Publication Type:Journal Article
Keywords: Artemisinin-based combination therapy; genetic diversity; kelch13; Plasmodium knowlesi; Sabah
From:Malaysian Journal of Microbiology 2023;19(no.6):602-609
CountryMalaysia
Language:English
Abstract: Aims:The kelch13 gene mutations of Plasmodium falciparum is associated with delayed parasite clearance after artemisinin-based combination therapy (ACT). It is unclear for P. knowlesi that is predominantly reported in Sabah. Therefore, this study aims to analyse the diversity of the P. knowlesi kelch13 gene in five divisions of Sabah.
Methodology and results: :Ninety-five blood samples infected with P. knowlesi were obtained. The DNA of P. knowlesi samples was extracted and the kelch13 gene was amplified. The amplicons were cloned and sequenced. The sequencing data were aligned and analysed using MEGA 11 and DnaSP v6 software. A phylogenetic tree was constructed using the Neighbour-joining approach, which showed a diverse clade of P. knowlesi in Sabah, with a nucleotide diversity (π) of 0.451 and a haplotype diversity of 0.947. The deduced amino acid sequences were classified into 14 haplotypes, providing evidence of distinct P. knowlesi lineages in Sabah. When compared to P. falciparum, the kelch13 sequences of P. knowlesi exhibited a higher π of 0.490 and haplotype diversity of 1.000, and similar mutations that conferred drug resistance to ACT in P. falciparum were detected in P. knowlesi in this study.
Conclusion, significance and impact of study: :The kelch13 gene of P. knowlesi isolates in Sabah has high nucleotide and haplotype diversities. Additionally, mutations conferring drug resistance to ACT in P. falciparum were identified in P. knowlesi in Sabah. The findings in this study can be used to better understand the emergence of drug resistance of P. knowlesi in Sabah.
Full text:20.2023my0064.pdf