Diversity pattern of Plasmodium knowlesi merozoite surface protein 4 (MSP4) in natural population of Malaysia.

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  • Author(s): Ahmed MA;Ahmed MA; Saif A; Saif A; Quan FS; Quan FS; Quan FS
  • Source:
    PloS one [PLoS One] 2019 Nov 21; Vol. 14 (11), pp. e0224743. Date of Electronic Publication: 2019 Nov 21 (Print Publication: 2019).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Genetic Variation*; Antigens, Protozoan/*genetics ; Malaria/*parasitology ; Plasmodium knowlesi/*genetics ; Protozoan Proteins/*genetics; Animals ; Antigens, Protozoan/isolation & purification ; Borneo ; DNA, Protozoan/genetics ; DNA, Protozoan/isolation & purification ; Genes, Protozoan/genetics ; Geography ; Humans ; Malaysia ; Merozoites/genetics ; Merozoites/isolation & purification ; Philippines ; Phylogeny ; Plasmodium knowlesi/isolation & purification ; Protozoan Proteins/isolation & purification ; Selection, Genetic ; Sequence Analysis, DNA
    • Abstract:
      Human infections due to the monkey malaria parasite Plasmodium knowlesi are increasingly being reported from Malaysia. The parasite causes high parasitaemia, severe and fatal malaria in humans thus there is a need for urgent measures for its control. The MSP4 is a potential vaccine candidate, which is well studied in Plasmodium falciparum and Plasmodium vivax; however, no study has been conducted in the orthologous gene of P. knowlesi. In this study, we investigated the level of polymorphisms, haplotypes, natural selection and population structure of full-length pkmsp4 in 32 clinical samples from Malaysian Borneo along with 4 lab-adapted strains. We found low levels of polymorphism across the gene with exon I showing higher diversity than the exon II. The C- terminal epidermal growth factor (EGF) domains and GPI-anchored region within exon II were mostly conserved with only 2 non-synonymous substitutions. Although 21 amino acid haplotypes were found, the frequency of mutation at the majority of the polymorphic positions was low. We found evidence of negative selection at the exon II of the gene indicating existence of functional constraints. Phylogenetic haplotype network analysis identified shared haplotypes and indicated geographical clustering of samples originating from Peninsular Malaysia and Malaysian Borneo. High population differentiation values were observed within parasite populations originating from Malaysian Borneo (Kapit, Sarikei and Betong) and laboratory-adapted strains obtained from Peninsular Malaysia and Philippines indicating distinct population structure. This is the first study to genetically characterize the full-length msp4 gene from clinical isolates of P. knowlesi from Malaysia and thus would be very useful for future rational vaccine studies. Further studies with higher number of samples and functional characterization of the protein will be necessary.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Antigens, Protozoan)
      0 (DNA, Protozoan)
      0 (Protozoan Proteins)
      0 (merozoite surface protein 4, Plasmodium)
    • Publication Date:
      Date Created: 20191122 Date Completed: 20200406 Latest Revision: 20200408
    • Publication Date:
      20240104
    • Accession Number:
      PMC6872184
    • Accession Number:
      10.1371/journal.pone.0224743
    • Accession Number:
      31751362