Allelic Diversity and Geographical Distribution of the Gene Encoding &amp;lt;i&amp;gt;Plasmodium falciparum&amp;lt;/i&amp;gt; Merozoite Surface Protein-3 in Thailand

Sawaswong, Vorthon; Simpalipan, Phumin; Siripoon, Napaporn; Harnyuttanakorn, Pongchai; Pattaradilokrat, Sittiporn

doi:10.3347/kjp.2015.53.2.177

Cited by 4 publications

(5 citation statements)

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“…Last but not least, the sequence analysis of the msp - 3 gene could infer the population structure of P. falciparum in Thailand, where the distribution pattern of MSP-3 variants depicts a differential genetic diversity among the populations in Thailand. In contrast to a previous study, in which msp - 3 alleles were classified into two types by PCR [ 34 ], the sequence information of msp - 3 showed that there were as many as five variants of MSP-3 in all of the parasite populations examined except for that in Ubon Ratchatani. This result indicates that the levels of genetic diversity of P. falciparum near the Thailand–Myanmar and Thailand–Cambodia borders were greater than that at the Thailand–Laos border.…”

Section: Discussioncontrasting

confidence: 91%

Genetic diversity of the merozoite surface protein-3 gene in Plasmodium falciparum populations in Thailand

Pattaradilokrat

Sawaswong

Simpalipan

et al. 2016

Malar J

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BackgroundAn effective malaria vaccine is an urgently needed tool to fight against human malaria, the most deadly parasitic disease of humans. One promising candidate is the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum. This antigenic protein, encoded by the merozoite surface protein (msp-3) gene, is polymorphic and classified according to size into the two allelic types of K1 and 3D7. A recent study revealed that both the K1 and 3D7 alleles co-circulated within P. falciparum populations in Thailand, but the extent of the sequence diversity and variation within each allelic type remains largely unknown.MethodsThe msp-3 gene was sequenced from 59 P. falciparum samples collected from five endemic areas (Mae Hong Son, Kanchanaburi, Ranong, Trat and Ubon Ratchathani) in Thailand and analysed for nucleotide sequence diversity, haplotype diversity and deduced amino acid sequence diversity. The gene was also subject to population genetic analysis (F st) and neutrality tests (Tajima’s D, Fu and Li D* and Fu and Li’ F* tests) to determine any signature of selection.ResultsThe sequence analyses revealed eight unique DNA haplotypes and seven amino acid sequence variants, with a haplotype and nucleotide diversity of 0.828 and 0.049, respectively. Neutrality tests indicated that the polymorphism detected in the alanine heptad repeat region of MSP-3 was maintained by positive diversifying selection, suggesting its role as a potential target of protective immune responses and supporting its role as a vaccine candidate. Comparison of MSP-3 variants among parasite populations in Thailand, India and Nigeria also inferred a close genetic relationship between P. falciparum populations in Asia.ConclusionThis study revealed the extent of the msp-3 gene diversity in P. falciparum in Thailand, providing the fundamental basis for the better design of future blood stage malaria vaccines against P. falciparum.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1566-1) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 91%

Genetic diversity of the merozoite surface protein-3 gene in Plasmodium falciparum populations in Thailand

Pattaradilokrat

Sawaswong

Simpalipan

et al. 2016

Malar J

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“…The Wright F st analysis also indicated that the population structure of P. falciparum in Southeast Asia, based on the AMA -1 gene, was significantly different from the populations in the Middle East, South Asia, Oceania, Africa and South America. This result was similar to a separate study using the P. falciparum merozoite surface protein-3 gene [ 49 , 50 ]. The population subdivision among Asia, Africa and South America has also been reported using whole genome sequence data [ 5 ].…”

Section: Discussionsupporting

confidence: 90%

“…The blood stage malaria parasites were subjected to in vitro cultivation and maintained at the Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. The species of the malaria parasites were confirmed by microscopic examination of thin blood films and by genotyping with genetic markers, including microsatellites [ 48 ] and the merozoite surface protein-1 (MSP-1) and merozoite surface protein-3 (MSP-3) genes [ 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

“…Merozoites of P. falciparum were expanded in the laboratory using a in vitro culture protocol. Once the levels of parasitemia reached 5–10%, the parasites were harvested and used for genomic DNA extraction using a phenol/chloroform extraction method [ 48 – 50 ]. In brief, the parasitized erythrocytes were lysed in 0.05% (w/v) saponin in phosphate buffered saline pH 7.4 and then incubated in lysis buffer overnight.…”

Section: Methodsmentioning

confidence: 99%

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Unraveling Haplotype Diversity of the Apical Membrane Antigen-1 Gene in Plasmodium falciparum Populations in Thailand

et al. 2018

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Development of an effective vaccine is critically needed for the prevention of malaria. One of the key antigens for malaria vaccines is the apical membrane antigen 1 (AMA-1) of the human malaria parasite Plasmodium falciparum, the surface protein for erythrocyte invasion of the parasite. The gene encoding AMA-1 has been sequenced from populations of P. falciparum worldwide, but the haplotype diversity of the gene in P. falciparum populations in the Greater Mekong Subregion (GMS), including Thailand, remains to be characterized. In the present study, the AMA-1 gene was PCR amplified and sequenced from the genomic DNA of 65 P. falciparum isolates from 5 endemic areas in Thailand. The nearly full-length 1,848 nucleotide sequence of AMA-1 was subjected to molecular analyses, including nucleotide sequence diversity, haplotype diversity and deduced amino acid sequence diversity and neutrality tests. Phylogenetic analysis and pairwise population differentiation (Fst indices) were performed to infer the population structure. The analyses identified 60 single nucleotide polymorphic loci, predominately located in domain I of AMA-1. A total of 31 unique AMA-1 haplotypes were identified, which included 11 novel ones. The phylogenetic tree of the AMA-1 haplotypes revealed multiple clades of AMA-1, each of which contained parasites of multiple geographical origins, consistent with the Fst indices indicating genetic homogeneity or gene flow among geographically distinct populations of P. falciparum in Thailand’s borders with Myanmar, Laos and Cambodia. In summary, the study revealed novel haplotypes and population structure needed for the further advancement of AMA-1-based malaria vaccines in the GMS.

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“…However, these vaccine candidate proteins are highly polymorphic in nature, mandating a detailed understanding of their diversity patterns through field studies in different geographical locations [ 21 , 22 ]. Among the established vaccine candidate antigens of P. falciparum , blood-stage antigens like MSPs have traditionally been given more importance; but other antigens like P. falciparum apical membrane antigen (PfAMA-1) also hold promise [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development

Nirmolia

Ahmed

Sathishkumar

et al. 2022

Malar J

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Background Malaria continues to be a major public health problem in the Northeastern part of India despite the implementation of vector control measures and changes in drug policies. To develop successful vaccines against malaria, it is important to assess the diversity of vaccine candidate antigens in field isolates. This study was done to assess the diversity of Plasmodium falciparum AMA-1 vaccine candidate antigen in a malaria-endemic region of Tripura in Northeast India and compare it with previously reported global isolates with a view to assess the feasibility of developing a universal vaccine based on this antigen. Methods Patients with fever and malaria-like illness were screened for malaria and P. falciparum positive cases were recruited for the current study. The diversity of PfAMA-1 vaccine candidate antigen was evaluated by nested PCR and RFLP. A selected number of samples were sequenced using the Sanger technique. Results Among 56 P. falciparum positive isolates, Pfama-1 was successfully amplified in 75% (n = 42) isolates. Allele frequencies of PfAMA-1 antigen were 16.6% (n = 7) for 3D7 allele and 33.3% (n = 14) in both K1 and HB3 alleles. DNA sequencing revealed 13 haplotypes in the Pfama-1 gene including three unique haplotypes not reported earlier. No unique amino-acid substitutions were found. Global analysis with 2761 sequences revealed 435 haplotypes with a very complex network composition and few clusters. Nucleotide diversity for Tripura (0.02582 ± 0.00160) showed concordance with South-East Asian isolates while recombination parameter (Rm = 8) was lower than previous reports from India. Population genetic structure showed moderate differentiation. Conclusions Besides documenting all previously reported allelic forms of the vaccine candidate PfAMA-1 antigen of P. falciparum, new haplotypes not reported earlier, were found in Tripura. Neutrality tests indicate that the Pfama-1 population in Tripura is under balancing selection. This is consistent with global patterns. However, the high haplotype diversity observed in the global Pfama-1 network analysis indicates that designing a universal vaccine based on this antigen may be difficult. This information adds to the existing database of genetic diversity of field isolates of P. falciparum and may be helpful in the development of more effective vaccines against the parasite.

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Allelic Diversity and Geographical Distribution of the Gene Encoding <i>Plasmodium falciparum</i> Merozoite Surface Protein-3 in Thailand

Cited by 4 publications

References 37 publications

Genetic diversity of the merozoite surface protein-3 gene in Plasmodium falciparum populations in Thailand

Genetic diversity of the merozoite surface protein-3 gene in Plasmodium falciparum populations in Thailand

Unraveling Haplotype Diversity of the Apical Membrane Antigen-1 Gene in Plasmodium falciparum Populations in Thailand

Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development

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