Genetic diversity of Plasmodium vivax and Plasmodium falciparum lactate dehydrogenases in Myanmar isolates.

Autor: Lee J; Department of Tropical Medicine and Inha Research Institute for Medical Science, Inha University School of Medicine, Incheon, Republic of Korea., Kim TI; Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, 52727, Republic of Korea.; Planning and Management Division, Nakdonggang National Institute of Biological Resources, Sangju, 37242, Republic of Korea., Lê HG; Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, 52727, Republic of Korea.; BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea., Yoo WG; Department of Medical Environmental Biology, Chung-Ang University College of Medicine, Seoul, 06974, Republic of Korea., Kang JM; Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, 52727, Republic of Korea.; BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea., Ahn SK; Department of Tropical Medicine and Inha Research Institute for Medical Science, Inha University School of Medicine, Incheon, Republic of Korea., Myint MK; Department of Medical Research Pyin Oo Lwin Branch, Pyin Oo Lwin, Myanmar., Lin K; Department of Medical Research Pyin Oo Lwin Branch, Pyin Oo Lwin, Myanmar., Kim TS; Department of Tropical Medicine and Inha Research Institute for Medical Science, Inha University School of Medicine, Incheon, Republic of Korea. tongsookim@inha.ac.kr., Na BK; Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, 52727, Republic of Korea. bkna@gnu.ac.kr.; BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea. bkna@gnu.ac.kr.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2020 Feb 04; Vol. 19 (1), pp. 60. Date of Electronic Publication: 2020 Feb 04.
DOI: 10.1186/s12936-020-3134-y
Abstrakt: Background: Plasmodium lactate dehydrogenase (pLDH) is a major target in diagnosing the erythrocytic stage of malaria parasites because it is highly expressed during blood-stage parasites and is distinguished from human LDH. Rapid diagnostic tests (RDTs) for malaria use pLDH as a target antigen; however, genetic variations in pLDH within the natural population threaten the efficacy of pLDH-based RDTs.
Methods: Genetic polymorphisms of Plasmodium vivax LDH (PvLDH) and Plasmodium falciparum LDH (PfLDH) in Myanmar isolates were analysed by nucleotide sequencing analysis. Genetic polymorphisms and the natural selection of PvLDH and PfLDH were analysed using DNASTAR, MEGA6, and DnaSP ver. 5.10.00 programs. The genetic diversity and natural selection of global PvLDH and PfLDH were also analysed. The haplotype network of global PvLDH and PfLDH was constructed using NETWORK ver. 5.0.0.3. Three-dimensional structures of PvLDH and PfLDH were built with YASARA Structure ver. 18.4.24 and the impact of mutations on structural change and stability was evaluated with SDM ver. 2, CUPSAT and MAESTROweb.
Results: Forty-nine PvLDH and 52 PfLDH sequences were obtained from Myanmar P. vivax and P. falciparum isolates. Non-synonymous nucleotide substitutions resulting in amino acid changes were identified in both Myanmar PvLDH and PfLDH. Amino acid changes were also identified in the global PvLDH and PfLDH populations, but they did not produce structural alterations in either protein. Low genetic diversity was observed in global PvLDH and PfLDH, which may be maintained by a strong purifying selection.
Conclusion: This study extends knowledge for genetic diversity and natural selection of global PvLDH and PfLDH. Although amino acid changes were observed in global PvLDH and PfLDH, they did not alter the conformational structures of the proteins. These suggest that PvLDH and PfLDH are genetically well-conserved in global populations, which indicates that they are suitable antigens for diagnostic purpose and attractive targets for drug development.
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje