23 results on '"Siegel, Sasha V"'
Search Results
2. Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites
- Author
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Siegel, Sasha V., Trimarsanto, Hidayat, Amato, Roberto, Murie, Kathryn, Taylor, Aimee R., Sutanto, Edwin, Kleinecke, Mariana, Whitton, Georgia, Watson, James A., Imwong, Mallika, Assefa, Ashenafi, Rahim, Awab Ghulam, Nguyen, Hoang Chau, Tran, Tinh Hien, Green, Justin A., Koh, Gavin C. K. W., White, Nicholas J., Day, Nicholas, Kwiatkowski, Dominic P., Rayner, Julian C., Price, Ric N., and Auburn, Sarah
- Published
- 2024
- Full Text
- View/download PDF
3. Author Correction: Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
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Proto, William R., Siegel, Sasha V., Dankwa, Selasi, Liu, Weimin, Kemp, Alison, Marsden, Sarah, Zenonos, Zenon A., Unwin, Steve, Sharp, Paul M., Wright, Gavin J., Hahn, Beatrice H., Duraisingh, Manoj T., and Rayner, Julian C.
- Published
- 2021
- Full Text
- View/download PDF
4. Single cell sequencing shines a light on malaria parasite relatedness in complex infections
- Author
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Siegel, Sasha V. and Rayner, Julian C.
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- 2020
- Full Text
- View/download PDF
5. First evidence of polychaete intermediate hosts for Neospirorchis spp. marine turtle blood flukes (Trematoda: Spirorchiidae)
- Author
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de Buron, Isaure, Colon, Beatrice L., Siegel, Sasha V., Oberstaller, Jenna, Rivero, Andrea, and Kyle, Dennis E.
- Published
- 2018
- Full Text
- View/download PDF
6. Blood flukes Cardicola parvus and C. laruei (Trematoda: Aporocotylidae): life cycles and cryptic infection in spotted seatrout, Cynoscion nebulosus (Teleost: Sciaenidae)
- Author
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Siegel, Sasha V., Rivero, Andrea V., Oberstaller, Jenna, Colon, Beatrice L., de Buron, Isaure, and Kyle, Dennis E.
- Published
- 2018
- Full Text
- View/download PDF
7. Analysis of Plasmodium vivax schizont transcriptomes from field isolates reveals heterogeneity of expression of genes involved in host-parasite interactions
- Author
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Siegel, Sasha V., Chappell, Lia, Hostetler, Jessica B., Amaratunga, Chanaki, Suon, Seila, Böhme, Ulrike, Berriman, Matthew, Fairhurst, Rick M., and Rayner, Julian C.
- Published
- 2020
- Full Text
- View/download PDF
8. Lineage-informative microhaplotypes for spatio-temporal surveillance of Plasmodium vivax malaria parasites
- Author
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Siegel, Sasha V, primary, Amato, Roberto, additional, Trimarsanto, Hidayat, additional, Sutanto, Edwin, additional, Kleinecke, Mariana, additional, Murie, Kathryn, additional, Whitton, Georgia, additional, Taylor, Aimee R, additional, Watson, James A, additional, Imwong, Mallika, additional, Assefa, Ashenafi, additional, Rahim, Awab Ghulam, additional, Chao, Nguyen Hoang, additional, Hien, Tran Tinh, additional, Green, Justin A, additional, Koh, Gavin, additional, White, Nicholas J, additional, Kwiatkowski, Dominic P, additional, Rayner, Julian C, additional, Price, Ric N, additional, and Auburn, Sarah, additional
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- 2023
- Full Text
- View/download PDF
9. Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
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Proto, William R., Siegel, Sasha V., Dankwa, Selasi, Liu, Weimin, Kemp, Alison, Marsden, Sarah, Zenonos, Zenon A., Unwin, Steve, Sharp, Paul M., Wright, Gavin J., Hahn, Beatrice H., Duraisingh, Manoj T., and Rayner, Julian C.
- Published
- 2019
- Full Text
- View/download PDF
10. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples
- Author
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Adam, Ishag, Alam, Mohammad Shafiul, Alemu, Sisay, Amaratunga, Chanaki, Amato, Roberto, Andrianaranjaka, Voahangy, Anstey, Nicholas M, Aseffa, Abraham, Ashley, Elizabeth, Assefa, Ashenafi, Auburn, Sarah, Barber, Bridget E, Barry, Alyssa, Batista Pereira, Dhelio, Cao, Jun, Chau, Nguyen Hoang, Chotivanich, Kesinee, Chu, Cindy, Dondorp, Arjen M, Drury, Eleanor, Echeverry, Diego F, Erko, Berhanu, Espino, Fe, Fairhurst, Rick, Faiz, Abdul, Fernanda Villegas, María, Gao, Qi, Golassa, Lemu, Goncalves, Sonia, Grigg, Matthew J, Hamedi, Yaghoob, Hien, Tran Tinh, Htut, Ye, Johnson, Kimberly J, Karunaweera, Nadira, Khan, Wasif, Krudsood, Srivicha, Kwiatkowski, Dominic P, Lacerda, Marcus, Ley, Benedikt, Lim, Pharath, Liu, Yaobao, Llanos-Cuentas, Alejandro, Lon, Chanthap, Lopera-Mesa, Tatiana, Marfurt, Jutta, Michon, Pascal, Miotto, Olivo, Mohammed, Rezika, Mueller, Ivo, Namaik-Larp, Chayadol, Newton, Paul N, Nguyen, Thuy-Nhien, Nosten, Francois, Noviyanti, Rintis, Pava, Zuleima, Pearson, Richard D, Petros, Beyene, Phyo, Aung P, Price, Ric N, Pukrittayakamee, Sasithon, Rahim, Awab Ghulam, Randrianarivelojosia, Milijaona, Rayner, Julian C, Rumaseb, Angela, Siegel, Sasha V, Simpson, Victoria J, Thriemer, Kamala, Tobon-Castano, Alberto, Trimarsanto, Hidayat, Urbano Ferreira, Marcelo, Vélez, Ivan D, Wangchuk, Sonam, Wellems, Thomas E, White, Nicholas J, William, Timothy, Yasnot, Maria F, Yilma, Daniel, Alam, Mohammad Shafiul [0000-0001-8330-5499], Ashley, Elizabeth [0000-0002-7620-4822], Barber, Bridget E [0000-0003-1066-7960], Batista Pereira, Dhelio [0000-0002-7761-5498], Chu, Cindy [0000-0001-9465-8214], Dondorp, Arjen M [0000-0001-5190-2395], Echeverry, Diego F [0000-0003-0301-4478], Espino, Fe [0000-0003-1690-1711], Faiz, Abdul [0000-0002-3460-7535], Golassa, Lemu [0000-0002-1216-8711], Grigg, Matthew J [0000-0001-9914-8352], Karunaweera, Nadira [0000-0003-3985-1817], Kwiatkowski, Dominic P [0000-0002-5023-0176], Ley, Benedikt [0000-0002-5734-0845], Miotto, Olivo [0000-0001-8060-6771], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Pearson, Richard D [0000-0002-7386-3566], Phyo, Aung P [0000-0002-0383-9624], Price, Ric N [0000-0003-2000-2874], Rayner, Julian C [0000-0002-9835-1014], Urbano Ferreira, Marcelo [0000-0002-5293-9090], Wellems, Thomas E [0000-0003-3899-8454], Yasnot, Maria F [0000-0001-8081-4212], Yilma, Daniel [0000-0001-6058-2696], and Apollo - University of Cambridge Repository
- Subjects
parasitic diseases ,Genomics ,Genomic Epidemiology ,Plasmodium vivax ,Malaria ,Data Resource - Abstract
This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.
- Published
- 2022
11. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples
- Author
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MalariaGEN, Adam, Ishag, Alam, Mohammad Shafiul, Alemu, Sisay, Amaratunga, Chanaki, Amato, Roberto, Andrianaranjaka, Voahangy, Anstey, Nicholas M, Aseffa, Abraham, Ashley, Elizabeth, Assefa, Ashenafi, Auburn, Sarah, Barber, Bridget E, Barry, Alyssa, Batista Pereira, Dhelio, Cao, Jun, Chau, Nguyen Hoang, Chotivanich, Kesinee, Chu, Cindy, Dondorp, Arjen M, Drury, Eleanor, Echeverry, Diego F, Erko, Berhanu, Espino, Fe, Fairhurst, Rick, Faiz, Abdul, Fernanda Villegas, María, Gao, Qi, Golassa, Lemu, Goncalves, Sonia, Grigg, Matthew J, Hamedi, Yaghoob, Hien, Tran Tinh, Htut, Ye, Johnson, Kimberly J, Karunaweera, Nadira, Khan, Wasif, Krudsood, Srivicha, Kwiatkowski, Dominic P, Lacerda, Marcus, Ley, Benedikt, Lim, Pharath, Liu, Yaobao, Llanos-Cuentas, Alejandro, Lon, Chanthap, Lopera-Mesa, Tatiana, Marfurt, Jutta, Michon, Pascal, Miotto, Olivo, Mohammed, Rezika, Mueller, Ivo, Namaik-Larp, Chayadol, Newton, Paul N, Nguyen, Thuy-Nhien, Nosten, Francois, Noviyanti, Rintis, Pava, Zuleima, Pearson, Richard D, Petros, Beyene, Phyo, Aung P, Price, Ric N, Pukrittayakamee, Sasithon, Rahim, Awab Ghulam, Randrianarivelojosia, Milijaona, Rayner, Julian C, Rumaseb, Angela, Siegel, Sasha V, Simpson, Victoria J, Thriemer, Kamala, Tobon-Castano, Alberto, Trimarsanto, Hidayat, Urbano Ferreira, Marcelo, Vélez, Ivan D, Wangchuk, Sonam, Wellems, Thomas E, White, Nicholas J, William, Timothy, Yasnot, Maria F, Yilma, Daniel, AII - Infectious diseases, Intensive Care Medicine, MalariaGEN, Alam, Mohammad Shafiul [0000-0001-8330-5499], Ashley, Elizabeth [0000-0002-7620-4822], Barber, Bridget E [0000-0003-1066-7960], Batista Pereira, Dhelio [0000-0002-7761-5498], Chu, Cindy [0000-0001-9465-8214], Dondorp, Arjen M [0000-0001-5190-2395], Echeverry, Diego F [0000-0003-0301-4478], Espino, Fe [0000-0003-1690-1711], Faiz, Abdul [0000-0002-3460-7535], Golassa, Lemu [0000-0002-1216-8711], Karunaweera, Nadira [0000-0003-3985-1817], Kwiatkowski, Dominic P [0000-0002-5023-0176], Ley, Benedikt [0000-0002-5734-0845], Miotto, Olivo [0000-0001-8060-6771], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Pearson, Richard D [0000-0002-7386-3566], Phyo, Aung P [0000-0002-0383-9624], Price, Ric N [0000-0003-2000-2874], Rayner, Julian C [0000-0002-9835-1014], Urbano Ferreira, Marcelo [0000-0002-5293-9090], Wellems, Thomas E [0000-0003-3899-8454], Yasnot, Maria F [0000-0001-8081-4212], Yilma, Daniel [0000-0001-6058-2696], and Apollo - University of Cambridge Repository
- Subjects
Data resource ,parasitic diseases ,Medicine (miscellaneous) ,Genomics ,Genomic epidemiology ,Plasmodium vivax ,General Biochemistry, Genetics and Molecular Biology ,Malaria - Abstract
This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.
- Published
- 2022
12. Analysis of Plasmodium vivax schizont transcriptomes from field isolates reveals heterogeneity of expression of genes involved in host-parasite interactions
- Author
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Siegel, Sasha V., primary, Chappell, Lia, additional, Hostetler, Jessica B., additional, Amaratunga, Chanaki, additional, Suon, Seila, additional, Böhme, Ulrike, additional, Berriman, Matthew, additional, Fairhurst, Rick M., additional, and Rayner, Julian C., additional
- Published
- 2020
- Full Text
- View/download PDF
13. Menoctone Resistance in Malaria Parasites Is Conferred by M133I Mutations in Cytochrome b That Are Transmissible through Mosquitoes
- Author
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Blake, Lynn D., primary, Johnson, Myles E., additional, Siegel, Sasha V., additional, McQueen, Adonis, additional, Iyamu, Iredia D., additional, Shaikh, Abdul Kadar, additional, Shultis, Michael W., additional, Manetsch, Roman, additional, and Kyle, Dennis E., additional
- Published
- 2017
- Full Text
- View/download PDF
14. Analysis of Plasmodium vivax schizont transcriptomes from field isolates reveals heterogeneity of expression of genes involved in host-parasite interactions
- Author
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Siegel, Sasha V., Chappell, Lia, Hostetler, Jessica B., Amaratunga, Chanaki, Suon, Seila, Böhme, Ulrike, Berriman, Matthew, Fairhurst, Rick M., and Rayner, Julian C.
- Subjects
631/208/199 ,631/326/417/2551 ,article ,3. Good health ,631/326/417 - Abstract
Funder: Division of Intramural Research, National Institute of Allergy and Infectious Diseases; doi: http://dx.doi.org/10.13039/100006492, Plasmodium vivax gene regulation remains difficult to study due to the lack of a robust in vitro culture method, low parasite densities in peripheral circulation and asynchronous parasite development. We adapted an RNA-seq protocol “DAFT-seq” to sequence the transcriptome of four P. vivax field isolates that were cultured for a short period ex vivo before using a density gradient for schizont enrichment. Transcription was detected from 78% of the PvP01 reference genome, despite being schizont-enriched samples. This extensive data was used to define thousands of 5′ and 3′ untranslated regions, some of which overlapped with neighbouring transcripts, and to improve the gene models of 352 genes, including identifying 20 novel gene transcripts. This dataset has also significantly increased the known amount of heterogeneity between P. vivax schizont transcriptomes from individual patients. The majority of genes found to be differentially expressed between the isolates lack Plasmodium falciparum homologs and are predicted to be involved in host-parasite interactions, with an enrichment in reticulocyte binding proteins, merozoite surface proteins and exported proteins with unknown function. An improved understanding of the diversity within P. vivax transcriptomes will be essential for the prioritisation of novel vaccine targets.
15. Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
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Proto, William R., Siegel, Sasha V., Dankwa, Selasi, Liu, Weimin, Kemp, Alison, Marsden, Sarah, Zenonos, Zenon A., Unwin, Steve, Sharp, Paul M., Wright, Gavin J., Hahn, Beatrice H., Duraisingh, Manoj T., and Rayner, Julian C.
- Subjects
13/31 ,82/80 ,631/326/417/1716 ,article ,692/699/255/1629 ,13/106 ,631/326/417/2548 ,13 ,3. Good health ,38/91 - Abstract
Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes. Here we show that all tested P. falciparum isolates contain an inactivating mutation in an erythrocyte invasion associated gene, PfEBA165, the homologues of which are intact in all ape-infective Laverania species. Recombinant EBA165 proteins only bind ape, not human, erythrocytes, and this specificity is due to differences in erythrocyte surface sialic acids. Correction of PfEBA165 inactivating mutations by genome editing yields viable parasites, but is associated with down regulation of both PfEBA165 and an adjacent invasion ligand, which suggests that PfEBA165 expression is incompatible with parasite growth in human erythrocytes. Pseudogenization of PfEBA165 may represent a key step in the emergence and evolution of P. falciparum.
16. Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
-
Proto, William R, Siegel, Sasha V, Dankwa, Selasi, Liu, Weimin, Kemp, Alison, Marsden, Sarah, Zenonos, Zenon A, Unwin, Steve, Sharp, Paul M, Wright, Gavin J, Hahn, Beatrice H, Duraisingh, Manoj T, and Rayner, Julian C
- Subjects
Gene Editing ,Erythrocytes ,Pan troglodytes ,Plasmodium falciparum ,Protozoan Proteins ,Host Specificity ,3. Good health ,Evolution, Molecular ,HEK293 Cells ,Loss of Function Mutation ,Sialic Acids ,Animals ,Humans ,CRISPR-Cas Systems ,Malaria, Falciparum ,Frameshift Mutation ,Cell Engineering - Abstract
Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes. Here we show that all tested P. falciparum isolates contain an inactivating mutation in an erythrocyte invasion associated gene, PfEBA165, the homologues of which are intact in all ape-infective Laverania species. Recombinant EBA165 proteins only bind ape, not human, erythrocytes, and this specificity is due to differences in erythrocyte surface sialic acids. Correction of PfEBA165 inactivating mutations by genome editing yields viable parasites, but is associated with down regulation of both PfEBA165 and an adjacent invasion ligand, which suggests that PfEBA165 expression is incompatible with parasite growth in human erythrocytes. Pseudogenization of PfEBA165 may represent a key step in the emergence and evolution of P. falciparum.
17. Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
-
Proto, William R., Siegel, Sasha V., Dankwa, Selasi, Liu, Weimin, Kemp, Alison, Marsden, Sarah, Zenonos, Zenon A., Unwin, Steve, Sharp, Paul M., Wright, Gavin J., Hahn, Beatrice H., Duraisingh, Manoj T., and Rayner, Julian C.
- Subjects
13/31 ,82/80 ,631/326/417/1716 ,article ,692/699/255/1629 ,13/106 ,631/326/417/2548 ,13 ,3. Good health ,38/91 - Abstract
Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes. Here we show that all tested P. falciparum isolates contain an inactivating mutation in an erythrocyte invasion associated gene, PfEBA165, the homologues of which are intact in all ape-infective Laverania species. Recombinant EBA165 proteins only bind ape, not human, erythrocytes, and this specificity is due to differences in erythrocyte surface sialic acids. Correction of PfEBA165 inactivating mutations by genome editing yields viable parasites, but is associated with down regulation of both PfEBA165 and an adjacent invasion ligand, which suggests that PfEBA165 expression is incompatible with parasite growth in human erythrocytes. Pseudogenization of PfEBA165 may represent a key step in the emergence and evolution of P. falciparum.
18. Analysis of Plasmodium vivax schizont transcriptomes from field isolates reveals heterogeneity of expression of genes involved in host-parasite interactions
- Author
-
Siegel, Sasha V., Chappell, Lia, Hostetler, Jessica B., Amaratunga, Chanaki, Suon, Seila, Böhme, Ulrike, Berriman, Matthew, Fairhurst, Rick M., and Rayner, Julian C.
- Subjects
631/208/199 ,631/326/417/2551 ,article ,3. Good health ,631/326/417 - Abstract
Funder: Division of Intramural Research, National Institute of Allergy and Infectious Diseases; doi: http://dx.doi.org/10.13039/100006492, Plasmodium vivax gene regulation remains difficult to study due to the lack of a robust in vitro culture method, low parasite densities in peripheral circulation and asynchronous parasite development. We adapted an RNA-seq protocol “DAFT-seq” to sequence the transcriptome of four P. vivax field isolates that were cultured for a short period ex vivo before using a density gradient for schizont enrichment. Transcription was detected from 78% of the PvP01 reference genome, despite being schizont-enriched samples. This extensive data was used to define thousands of 5′ and 3′ untranslated regions, some of which overlapped with neighbouring transcripts, and to improve the gene models of 352 genes, including identifying 20 novel gene transcripts. This dataset has also significantly increased the known amount of heterogeneity between P. vivax schizont transcriptomes from individual patients. The majority of genes found to be differentially expressed between the isolates lack Plasmodium falciparum homologs and are predicted to be involved in host-parasite interactions, with an enrichment in reticulocyte binding proteins, merozoite surface proteins and exported proteins with unknown function. An improved understanding of the diversity within P. vivax transcriptomes will be essential for the prioritisation of novel vaccine targets.
19. Analysis of Plasmodium vivax schizont transcriptomes from field isolates reveals heterogeneity of expression of genes involved in host-parasite interactions
- Author
-
Siegel, Sasha V, Chappell, Lia, Hostetler, Jessica B, Amaratunga, Chanaki, Suon, Seila, Böhme, Ulrike, Berriman, Matthew, Fairhurst, Rick M, and Rayner, Julian C
- Subjects
Gene Expression Regulation ,Merozoites ,parasitic diseases ,Schizonts ,Malaria, Vivax ,Humans ,Plasmodium vivax ,Transcriptome ,3. Good health ,Host-Parasite Interactions - Abstract
Plasmodium vivax gene regulation remains difficult to study due to the lack of a robust in vitro culture method, low parasite densities in peripheral circulation and asynchronous parasite development. We adapted an RNA-seq protocol "DAFT-seq" to sequence the transcriptome of four P. vivax field isolates that were cultured for a short period ex vivo before using a density gradient for schizont enrichment. Transcription was detected from 78% of the PvP01 reference genome, despite being schizont-enriched samples. This extensive data was used to define thousands of 5' and 3' untranslated regions, some of which overlapped with neighbouring transcripts, and to improve the gene models of 352 genes, including identifying 20 novel gene transcripts. This dataset has also significantly increased the known amount of heterogeneity between P. vivax schizont transcriptomes from individual patients. The majority of genes found to be differentially expressed between the isolates lack Plasmodium falciparum homologs and are predicted to be involved in host-parasite interactions, with an enrichment in reticulocyte binding proteins, merozoite surface proteins and exported proteins with unknown function. An improved understanding of the diversity within P. vivax transcriptomes will be essential for the prioritisation of novel vaccine targets.
20. Menoctone Resistance in Malaria Parasites Is Conferred by M133I Mutations in Cytochrome bThat Are Transmissible through Mosquitoes
- Author
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Blake, Lynn D., Johnson, Myles E., Siegel, Sasha V., McQueen, Adonis, Iyamu, Iredia D., Shaikh, Abdul Kadar, Shultis, Michael W., Manetsch, Roman, and Kyle, Dennis E.
- Abstract
ABSTRACTMalaria-related mortality has slowly decreased over the past decade; however, eradication of malaria requires the development of new antimalarial chemotherapies that target liver stages of the parasite and combat the emergence of drug resistance. The diminishing arsenal of anti-liver-stage compounds sparked our interest in reviving the old and previously abandoned compound menoctone. In support of these studies, we developed a new convergent synthesis method that was facile, required fewer steps, produced better yields, and utilized less expensive reagents than the previously published method. Menoctone proved to be highly potent against liver stages of Plasmodium berghei(50 percent inhibitory concentration [IC50] = 0.41 nM) and erythrocytic stages of Plasmodium falciparum(113 nM). We selected for resistance to menoctone and found M133I mutations in cytochrome bof both P. falciparumand P. berghei. The same mutation has been observed previously in atovaquone resistance, and we confirmed cross-resistance between menoctone and atovaquone in vitro(for P. falciparum) and in vivo(for P. berghei). Finally, we assessed the transmission potential of menoctone-resistant P. bergheiand found that the M133I mutant parasites were readily transmitted from mouse to mosquitoes and back to mice. In each step, the M133I mutation in cytochrome b, inducing menoctone resistance, was confirmed. In summary, this study is the first to show the mechanism of resistance to menoctone and that menoctone and atovaquone resistance is transmissible through mosquitoes.
- Published
- 2017
- Full Text
- View/download PDF
21. Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand
- Author
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Manoj T. Duraisingh, Alison Kemp, Julian C. Rayner, Selasi Dankwa, William R. Proto, Paul M. Sharp, Gavin J. Wright, Zenon A. Zenonos, Steve Unwin, Weimin Liu, Sasha V. Siegel, Sarah Marsden, Beatrice H. Hahn, Proto, William R [0000-0003-2311-920X], Siegel, Sasha V [0000-0002-1458-4348], Dankwa, Selasi [0000-0002-1837-2924], Sharp, Paul M [0000-0001-9771-543X], Hahn, Beatrice H [0000-0002-9400-9887], Rayner, Julian C [0000-0002-9835-1014], Apollo - University of Cambridge Repository, Proto, William R. [0000-0003-2311-920X], Siegel, Sasha V. [0000-0002-1458-4348], Sharp, Paul M. [0000-0001-9771-543X], Hahn, Beatrice H. [0000-0002-9400-9887], and Rayner, Julian C. [0000-0002-9835-1014]
- Subjects
0301 basic medicine ,Erythrocytes ,Protozoan Proteins ,General Physics and Astronomy ,medicine.disease_cause ,13 ,law.invention ,0302 clinical medicine ,law ,Loss of Function Mutation ,631/326/417/1716 ,Malaria, Falciparum ,lcsh:Science ,Frameshift Mutation ,Cell Engineering ,Genetics ,Gene Editing ,Mutation ,Multidisciplinary ,biology ,article ,Ligand (biochemistry) ,3. Good health ,Parasite biology ,13/31 ,Parasite evolution ,Recombinant DNA ,Pan troglodytes ,Science ,Plasmodium falciparum ,13/106 ,General Biochemistry, Genetics and Molecular Biology ,Laverania ,Host Specificity ,Frameshift mutation ,38/91 ,82/80 ,Evolution, Molecular ,03 medical and health sciences ,parasitic diseases ,medicine ,692/699/255/1629 ,Animals ,Humans ,631/326/417/2548 ,Gene ,HEK 293 cells ,General Chemistry ,biology.organism_classification ,Malaria ,030104 developmental biology ,HEK293 Cells ,Sialic Acids ,lcsh:Q ,CRISPR-Cas Systems ,030217 neurology & neurosurgery - Abstract
Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes. Here we show that all tested P. falciparum isolates contain an inactivating mutation in an erythrocyte invasion associated gene, PfEBA165, the homologues of which are intact in all ape-infective Laverania species. Recombinant EBA165 proteins only bind ape, not human, erythrocytes, and this specificity is due to differences in erythrocyte surface sialic acids. Correction of PfEBA165 inactivating mutations by genome editing yields viable parasites, but is associated with down regulation of both PfEBA165 and an adjacent invasion ligand, which suggests that PfEBA165 expression is incompatible with parasite growth in human erythrocytes. Pseudogenization of PfEBA165 may represent a key step in the emergence and evolution of P. falciparum., Here, Proto et al. show that human infective Plasmodium falciparum isolates contain an inactivating mutation in the erythrocyte invasion associated gene PfEBA165, while homologues of ape-infective Laverania species are intact, and that expression of intact PfEBA165 is incompatible with parasite growth in human erythrocytes.
- Published
- 2019
22. Lineage-informative microhaplotypes for spatio-temporal surveillance of Plasmodium vivax malaria parasites.
- Author
-
Siegel SV, Amato R, Trimarsanto H, Sutanto E, Kleinecke M, Murie K, Whitton G, Taylor AR, Watson JA, Imwong M, Assefa A, Rahim AG, Chau NH, Hien TT, Green JA, Koh G, White NJ, Day N, Kwiatkowski DP, Rayner JC, Price RN, and Auburn S
- Abstract
Challenges in understanding the origin of recurrent Plasmodium vivax infections constrains the surveillance of antimalarial efficacy and transmission of this neglected parasite. Recurrent infections within an individual may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or new inoculations (reinfection). Molecular inference of familial relatedness (identity-by-descent or IBD) based on whole genome sequence data, together with analysis of the intervals between parasitaemic episodes ("time-to-event" analysis), can help resolve the probable origin of recurrences. Whole genome sequencing of predominantly low-density P. vivax infections is challenging, so an accurate and scalable genotyping method to determine the origins of recurrent parasitaemia would be of significant benefit. We have developed a P. vivax genome-wide informatics pipeline to select specific microhaplotype panels that can capture IBD within small, amplifiable segments of the genome. Using a global set of 615 P. vivax genomes, we derived a panel of 100 microhaplotypes, each comprising 3-10 high frequency SNPs within <200 bp sequence windows. This panel exhibits high diversity in regions of the Asia-Pacific, Latin America and the horn of Africa (median H
E = 0.70-0.81) and it captured 89% (273/307) of the polyclonal infections detected with genome-wide datasets. Using data simulations, we demonstrate lower error in estimating pairwise IBD using microhaplotypes, relative to traditional biallelic SNP barcodes. Our panel exhibited high accuracy in predicting the country of origin (median Matthew's correlation coefficient >0.9 in 90% countries tested) and it also captured local infection outbreak and bottlenecking events. The informatics pipeline is available open-source and yields microhaplotypes that can be readily transferred to high-throughput amplicon sequencing assays for surveillance in malaria-endemic regions.- Published
- 2023
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23. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples.
- Author
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Adam I, Alam MS, Alemu S, Amaratunga C, Amato R, Andrianaranjaka V, Anstey NM, Aseffa A, Ashley E, Assefa A, Auburn S, Barber BE, Barry A, Batista Pereira D, Cao J, Chau NH, Chotivanich K, Chu C, Dondorp AM, Drury E, Echeverry DF, Erko B, Espino F, Fairhurst R, Faiz A, Fernanda Villegas M, Gao Q, Golassa L, Goncalves S, Grigg MJ, Hamedi Y, Hien TT, Htut Y, Johnson KJ, Karunaweera N, Khan W, Krudsood S, Kwiatkowski DP, Lacerda M, Ley B, Lim P, Liu Y, Llanos-Cuentas A, Lon C, Lopera-Mesa T, Marfurt J, Michon P, Miotto O, Mohammed R, Mueller I, Namaik-Larp C, Newton PN, Nguyen TN, Nosten F, Noviyanti R, Pava Z, Pearson RD, Petros B, Phyo AP, Price RN, Pukrittayakamee S, Rahim AG, Randrianarivelojosia M, Rayner JC, Rumaseb A, Siegel SV, Simpson VJ, Thriemer K, Tobon-Castano A, Trimarsanto H, Urbano Ferreira M, Vélez ID, Wangchuk S, Wellems TE, White NJ, William T, Yasnot MF, and Yilma D
- Abstract
This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr , dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 MalariaGEN et al.)
- Published
- 2022
- Full Text
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