Leveraging genome editing to functionally evaluate Plasmodium diversity

Thiam, Laty G.; Mangou, Khadidiatou; Ba, Aboubacar; Mbengue, Alassane; Bei, Amy K.

doi:10.1016/j.pt.2022.03.005

Cited by 5 publications

(4 citation statements)

References 100 publications

(114 reference statements)

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“…Further population genomic studies of Poc and Pow should employ a larger selection of isolates from a greater geographic range, especially including Asia, and take advantage of new reference genome assemblies to build on these insights. Functional investigation into the genes showing signatures of selection, including via gene editing of closely related Plasmodium species, 55 is also a necessary step toward substantiating the biological relevance of these loci, with implications for transmission prevention, treatment strategies, and vaccine development for P. ovale . Finally, cataloging genome-wide diversity facilitates the design of targeted genotyping methods that can efficiently characterize the epidemiology of these understudied parasite species.…”

Section: Discussionmentioning

confidence: 99%

Population genomics ofPlasmodium ovalespecies in sub-Saharan Africa

Carey-Ewend,

Popkin-Hall,

Simkin

et al. 2024

Preprint

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Plasmodium ovale curtisi(Poc)andPlasmodium ovale wallikeri(Pow) are relapsing malaria parasites endemic to Africa and Asia that were previously thought to represent a single species. Amid increasing detection of ovale malaria in sub-Saharan Africa, we performed a population genomic study of both species across the continent. We conducted whole-genome sequencing of 25 isolates from central and east Africa and analyzed them alongside four previously published west and central African genomes. Isolates were predominantly monoclonal (27/29), with their genetic similarity aligning with geography.Powshowed lower average nucleotide diversity (1.9×10-4) across the genome compared toPoc(2.8×10-4) (p < 0.0001). Signatures of selective sweeps involving the dihydrofolate reductase gene were found in both species, as were signs of balancing selection at the merozoite surface protein 1 gene. Differences in the nucleotide diversity ofPocandPowmay reflect unique demographic history, even as similar selective forces facilitate their resilience to malaria control interventions.

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Section: Discussionmentioning

confidence: 99%

Population genomics ofPlasmodium ovalespecies in sub-Saharan Africa

Carey-Ewend,

Popkin-Hall,

Simkin

et al. 2024

Preprint

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“…For instance, epistasis studies on Toxoplasma with the help of CRISPR screens have aided in better understanding of genetic interactions, and the genes that enable the parasite to thrive within a variety of different hosts (Young et al 2019 ). Similarly, the CRISPR-aided screening has helped in the determination of functional genes in Plasmodium and related therapeutic and vaccine candidates in this apicomplexan (Thiam et al 2022 ). CRISPR has been employed to edit the germ cell lines in chicken, in order to enhance desirable traits related to meat and egg production (Khwatenge and Nahashon 2021 ).…”

Section: Opportunities (The Way Forward)mentioning

confidence: 99%

Vaccines against chicken coccidiosis with particular reference to previous decade: progress, challenges, and opportunities

et al. 2022

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Chicken coccidiosis is an economically significant disease of commercial chicken industry accounting for losses of more than £10.4 billion (according to 2016 prices). Additionally, the costs incurred in prophylaxis and therapeutics against chicken coccidiosis in developing countries (for instance Pakistan according to 2018 prices) reached US $45,000.00 while production losses for various categories of chicken ranges 104.74 to US $2,750,779.00. The infection has been reported from all types of commercial chickens (broiler, layer, breeder) having a range of reported prevalence of 7–90%. The concern of resistance towards major anticoccidials has provided a way forward to vaccine research and development. For prophylaxis of chicken coccidiosis, live virulent, attenuated, ionophore tolerant strains and recombinant vaccines have been extensively trialed and commercialized. Eimeria antigens and novel vaccine adjuvants have elicited the protective efficacy against coccidial challenge. The cost of production and achieving robust immune responses in birds are major challenges for commercial vaccine production. In the future, research should be focused on the development of multivalent anticoccidial vaccines for commercial poultry. Efforts should also be made on the discovery of novel antigens for incorporation into vaccine designs which might be more effective against multiple Eimeria species. This review presents a recap to the overall progress against chicken Eimeria with particular reference to previous decade. The article presents critical analysis of potential areas for future research in chicken Eimeria vaccine development.

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“…Malaria control is becoming more di cult as parasites develop resistance to commonly used antimalarial drugs and vectors develop insecticide resistance (Guyant P et al, 2015). This is due to genetic polymorphisms, which result in a large variety of functionally and antigenically different parasites (Thiam et al, 2022). P. falciparum is the most virulent malaria parasite species (Sourabh et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Merozoite surface protein 2 polymorphism of Plasmodium falciparum isolates in a selected malarious area of Northwest Ethiopia

Ashagre,

Dinsa,

Mekonnen

et al. 2024

Preprint

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Background The genetic diversity of Plasmodium falciparum provides the parasite with many effective immune evasion and drug resistance mechanisms. This phenomenon is a major problem in eradicating malaria globally. This study aimed to assess merozoite surface protein 2 polymorphisms in P. falciparum isolates from Northwest Ethiopia. Method A cross-sectional study was conducted to assess merozoite surface protein 2 polymorphisms in P. falciparum isolates from selected malarious areas in Northwest Ethiopia from April to June 2021. A convenience sampling technique was used to select a total of 150 study participants. A finger prick blood sample was collected for the preparation of blood films and dried blood spots for molecular genotyping. The Merozoite surface protein 2 allele frequency and multiplicity of infection were computed. Spearman's rank coefficients were used to assess the associations between the multiplicity of infection and parasite density and age. A P value < 0.05 was considered to indicate statistical significance. Result Polymorphism analysis was performed on 126 P. falciparum isolates. There were 38 different merozoite surface protein 2 alleles, 20 of which corresponded to the IC/3D7 allelic family and 18 to the FC27 allelic family. The majority of the isolates contained multiple infections, and the mean multiplicity of infection was 3.46. There was no statistically significant difference in the multiplicity of infection in relation to the age of patients (P = 0.646). However, a statistically significant correlation was found between parasite density and the multiplicity of infection (P = 0.046). The heterozygosity index for merozoite surface protein 2 was 0.948. Conclusion This study showed that P. falciparum isolates contain multiple genotypes with a high multiplicity of infections, suggesting the presence of extensive genetic diversity and mixed-strain infections. This could reflect a high level of malaria transmission intensity, which requires more effort to control malaria transmission in the study area.

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Leveraging genome editing to functionally evaluate Plasmodium diversity

Cited by 5 publications

References 100 publications

Population genomics ofPlasmodium ovalespecies in sub-Saharan Africa

Population genomics ofPlasmodium ovalespecies in sub-Saharan Africa

Vaccines against chicken coccidiosis with particular reference to previous decade: progress, challenges, and opportunities

Merozoite surface protein 2 polymorphism of Plasmodium falciparum isolates in a selected malarious area of Northwest Ethiopia

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