Phylogeographic Evidence for 2 Genetically Distinct Zoonotic<i>Plasmodium knowlesi</i>Parasites, Malaysia

Yusof, Ruhani; Ahmed, Atique; Jelip, Jenarun; Ngian, Hie Ung; Mustakim, Sahlawati; Hussin, Hani Mat; Fong, Mun Yik; Mahmud, Rohela; Sitam, Frankie Anak Thomas; Japning, J. Rovie-Ryan; Snounou, Georges; Escalante, Ananías A.; Lau, Yee Ling

doi:10.3201/eid2208.151885

Cited by 50 publications

(52 citation statements)

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“…The Philippine, MR4 and the Hackeri Strains formed a separate group along with Malaysian Borneo isolates. The distinct sub-populations observed in other invasion gene of P. knowlesi like MSP1P, DBPRII, NBPXA and TRAP was not observed in MSP7D [23, 25–27, 31, 49]. (Fig.5).…”

Section: Resultsmentioning

confidence: 90%

“…P. knowlesi has a 24-hour erythrocytic cycle thus rapid increase in parasitaemia has been associated with the development of severe malaria and also a common cause for severe and fatal malaria in Malaysian Borneo [3, 20–22]. Studies on mitochondrial and ssrRNA genes in P. knowlesi from patients and wild macaques identified two distinct sub-populations which clustered geographically to Peninsular Malaysia and Malaysian Borneo [23]. Additionally, genetic and genomic studies from Malaysia identified 3 distinct sub-populations; two originating from Sarawak and one from Peninsular Malaysia [24–27] thereby highlighting the complexity of infections in humans and the challenges for control as well as vaccine design.…”

Section: Introductionmentioning

confidence: 99%

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Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)

Ahmed

Quan

2019

Preprint

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BackgroundHigh proportion of human cases due to the simian malaria parasite Plasmodium knowlesi in Malaysia has been a cause of concern, as it can be severe and fatal. Merozoite surface protein 7 (MSP7) is a multigene family which forms a non-covalent complex with MSP-1 prior to receptor-ligand recognition in Plasmodium falciparum and thus an important antigen for vaccine development. However, no study has been done in any of the ortholog family members in Plasmodium knowlesi from clinical samples. Thus in this study we investigated the level of polymorphism, haplotypes, and natural selection acting at the pkmsp-7D gene in clinical samples from Malaysia.MethodsWe analyzed 36 full-length pkmsp7D gene sequences (along with the reference H-strain: PKNH_1266000) which were orthologous to pvmsp7H (PVX_082680) from clinical isolates of Malaysia available from public databases. Population genetic, evolutionary and phylogenetic analyses were performed to determine the level of genetic diversity, polymorphism, recombination and natural selection.ResultsAnalysis of 36 full-length pkmsp7D sequences identified 147 SNPs (91 non-synonymous and 56 synonymous substitutions). Nucleotide diversity across the full-length gene was higher than its ortholog in P. vivax (msp7H). Region-wise analysis of the gene indicated that the nucleotide diversity at the central region was very high (π = 0.14) compared to the 5’ and 3’ regions. Most hyper-variable SNPs were detected at the central domain. Multiple test for natural selection indicated the central region was under strong positive natural selection however, the 5’ and 3’ regions were under negative/purifying selection. Evidence of intragenic recombination were detected at the central region of the gene. Phylogenetic analysis using full-length msp7D genes indicated there was no geographical clustering of parasite population.ConclusionsHigh genetic diversity with hyper-variable SNPs and strong evidence of positive natural selection at the central region of MSP7D indicated exposure of the region to host immune pressure. Negative selection at the 5’ and the 3’ regions of MSP7D might be because of functional constraints at the unexposed regions during the merozoite invasion process of P. knowlesi. No evidence of geographical clustering among the clinical isolates from Malaysia indicated uniform selection pressure in all populations. These findings highlight the further evaluation of the regions and functional characterization of the protein as a potential blood stage vaccine candidate for P. knowlesi.

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Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)

Ahmed

Quan

2019

Preprint

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“…Human infections in Malaysian Borneo, the portion of Malaysia on the island of Borneo, have divergent genetic subpopulations that are seen in the different macaque species locally, indicating that 2 independent zoonoses may be occurring sympatrically ( 9 ). Noticeable geographic differentiation of parasites between Malaysian Borneo and peninsular Malaysia was also evident in microsatellite analysis; separate studies have revealed divergence between the 2 regions at unlinked genes encoding the normocyte binding protein ( 10 – 12 ) and the Duffy binding protein ( 13 , 14 ), as well as the 18S rRNA and mitochondrial cytochrome oxidase subunit 1 ( 15 ). Whole-genome sequencing has confirmed the presence of 2 divergent subpopulations of P. knowlesi in Malaysian Borneo and revealed a third divergent cluster of laboratory isolates maintained in laboratories since the 1960s; most of these were recorded to have originated from peninsular Malaysia ( 16 ).…”

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confidence: 93%

Three Divergent Subpopulations of the Malaria ParasitePlasmodium knowlesi

Divis¹,

Lin²,

Rovie-Ryan³

et al. 2017

Emerg. Infect. Dis.

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Multilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P. knowlesi infections (obtained from 134 humans and 48 wild macaques) from diverse areas of Malaysia, first analyzed separately and then in combination with previous data. All analyses confirmed 2 divergent clusters of human cases in Malaysian Borneo, associated with long-tailed macaques and pig-tailed macaques, and a third cluster in humans and most macaques in peninsular Malaysia. High levels of pairwise divergence between each of these sympatric and allopatric subpopulations have implications for the epidemiology and control of this zoonotic species.

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“…(C) Inhibition of P cynomolgi countries. [19][20][21] By contrast, to date, only 1 case of zoonotic P cynomolgi has been reported recently from Malaysia, 22 and it came to light solely through careful molecular analysis. Three interrelated factors might account for the disparity in the observed prevalence of zoonotic infections for these 2 species that have similar high prevalence in their natural hosts.…”

Section: Introductionmentioning

confidence: 99%

Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

Kosaisavee

Suwanarusk

Chua

et al. 2017

Blood

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Key Points• Zoonotic P cynomolgi switches red cell tropism for reticulocytes expressing Trf1 (CD71 1 ) and DARC (CD234 1 ). • In the human host, P cynomolgi displays an almost identical rheopathobiology to P vivax.Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi-infected human reticulocytes that are strikingly similar to those observed for P vivax. These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.

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Phylogeographic Evidence for 2 Genetically Distinct ZoonoticPlasmodium knowlesiParasites, Malaysia

Abstract: Sequence analyses of genes derived from human and macaque samples led to the proposal that 2 distinct types exist.

Cited by 50 publications

References 28 publications

Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)

Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)

Three Divergent Subpopulations of the Malaria ParasitePlasmodium knowlesi

Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

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