Epigenetically conferred ring-stage survival in Plasmodium falciparum against artemisinin treatment
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ABSTRACT:
PROVIDER: PRJNA1031577 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:To investigate the artemisinin resistance mechanism, we conducted a systematical evaluation of histone acetyltransferase expression in 45 cloned P. falciparum parasites and 30 wild-type field isolates. Remarkably, PfMYST, a member of the histone acetyltransferase MYST family, emerged as the sole candidate significantly associated with prolonged ring-survive of parasites. CHIP-seq analysis revealed PfMYST’s pivotal role in mediating histone modifications, particularly in H4K5ac and H4K8ac, within the P. falciparum genome. Through single-cell RNA sequence and conditional knockdown approaches, we identified and functionally validated PfMYST-targeted genes contributing to Plasmodium’s adaptive artemisinin resistance.
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Project description:To investigate the artemisinin resistance mechanism, we conducted a systematical evaluation of histone acetyltransferase expression in 45 cloned P. falciparum parasites and 30 wild-type field isolates. Remarkably, PfMYST, a member of the histone acetyltransferase MYST family, emerged as the sole candidate significantly associated with prolonged ring-survive of parasites. CHIP-seq analysis revealed PfMYST’s pivotal role in mediating histone modifications, particularly in H4K5ac and H4K8ac, within the P. falciparum genome. Through single-cell RNA sequence and conditional knockdown approaches, we identified and functionally validated PfMYST-targeted genes contributing to Plasmodium’s adaptive artemisinin resistance.
2025-07-03 | GSE246114 | GEO
Project description:To investigate the artemisinin resistance mechanism, we conducted a systematical evaluation of histone acetyltransferase expression in 45 cloned P. falciparum parasites and 30 wild-type field isolates. Remarkably, PfMYST, a member of the histone acetyltransferase MYST family, emerged as the sole candidate significantly associated with prolonged ring-survive of parasites. WGS analysis confirmed the genomic consistency among different parasite subclones. CHIP-seq analysis revealed PfMYST’s pivotal role in mediating histone modifications, particularly in H4K5ac and H4K8ac, within the P. falciparum genome. Through single-cell RNA sequence and conditional knockdown approaches, we identified and functionally validated PfMYST-targeted genes contributing to Plasmodium’s adaptive artemisinin resistance.
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Project description:Artemisinin resistance in Plasmodium falciparum malaria has emerged in western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. Using DNA microarrays we identify key features of a transcriptional profile that are associated with the delayed parasite clearance phenotype. These include reduced expression of several basic metabolic and cellular pathways in the early stages, and increased expression of essentially all functionalities associated with protein metabolism in the later stages of P. falciparum intraerythrocytic development. This is consistent with the reduced ring stage susceptibility that characterizes artemisinin resistant P. falciparum. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of several regulatory proteins such as transcription factors of chromatin remodeling associated factors. In addition, the artemisinin resistant phenotype is strongly associated with a specific pattern of copy number variations, some of which are linked with differential expression of several regulatory proteins such as histone 4 and zinc permease. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides a set of candidate genes for further investigation.
2010-12-07 | GSE25879 | GEO
Project description:Artemisinin resistance in Plasmodium falciparum malaria has emerged in western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. Using DNA microarrays we identify key features of a transcriptional profile that are associated with the delayed parasite clearance phenotype. These include reduced expression of several basic metabolic and cellular pathways in the early stages, and increased expression of essentially all functionalities associated with protein metabolism in the later stages of P. falciparum intraerythrocytic development. This is consistent with the reduced ring stage susceptibility that characterizes artemisinin resistant P. falciparum. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of several regulatory proteins such as transcription factors of chromatin remodeling associated factors. In addition, the artemisinin resistant phenotype is strongly associated with a specific pattern of copy number variations, some of which are linked with differential expression of several regulatory proteins such as histone 4 and zinc permease. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides a set of candidate genes for further investigation.
2010-12-07 | GSE25878 | GEO
Project description:Artemisinin resistance in Plasmodium falciparum malaria has emerged in western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. Using DNA microarrays we identify key features of a transcriptional profile that are associated with the delayed parasite clearance phenotype. These include reduced expression of several basic metabolic and cellular pathways in the early stages, and increased expression of essentially all functionalities associated with protein metabolism in the later stages of P. falciparum intraerythrocytic development. This is consistent with the reduced ring stage susceptibility that characterizes artemisinin resistant P. falciparum. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of several regulatory proteins such as transcription factors of chromatin remodeling associated factors. In addition, the artemisinin resistant phenotype is strongly associated with a specific pattern of copy number variations, some of which are linked with differential expression of several regulatory proteins such as histone 4 and zinc permease. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides a set of candidate genes for further investigation. 6 P. falciparum parasites (field isolates) which are either Artemsinin resistant or sensitive from 3 study sites (Pailin in Cambodia, Xepon in Laos, Mae Sot in Thailand) were sampled and harvested for genomic DNA. gDNA from a total of 6 samples were extracted by phenol chloroform. Synthesis of labelled target DNA was carried out as previously described: Mackinnon, M.J. et al. Comparative transcriptional and genomic analysis of Plasmodium falciparum field isolates. PLoS Pathog 5, e1000644 (2009), and used in comparative genomic microarray hybridizations (CGH).
2010-12-07 | E-GEOD-25879 | biostudies-arrayexpress
Project description:Artemisinin resistance in Plasmodium falciparum malaria has emerged in western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. Using DNA microarrays we identify key features of a transcriptional profile that are associated with the delayed parasite clearance phenotype. These include reduced expression of several basic metabolic and cellular pathways in the early stages, and increased expression of essentially all functionalities associated with protein metabolism in the later stages of P. falciparum intraerythrocytic development. This is consistent with the reduced ring stage susceptibility that characterizes artemisinin resistant P. falciparum. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of several regulatory proteins such as transcription factors of chromatin remodeling associated factors. In addition, the artemisinin resistant phenotype is strongly associated with a specific pattern of copy number variations, some of which are linked with differential expression of several regulatory proteins such as histone 4 and zinc permease. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides a set of candidate genes for further investigation. 11 P. falciparum parasites (field isolates) which are either Artemsinin resistant or sensitive from 3 study sites (Pailin in Cambodia, Xepon in Laos, Mae Sot in Thailand) were sampled, grown ex-vivo over 48 hours and harvested at regular intervals. RNA from a total of 91 samples were extracted. Synthesis of target DNA was carried out as previously described: Mackinnon, M.J. et al. Comparative transcriptional and genomic analysis of Plasmodium falciparum field isolates. PLoS Pathog 5, e1000644 (2009), and used in microarray hybridizations.
2010-12-07 | E-GEOD-25878 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25878: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription (expression) GSE25879: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription (CGH) Refer to individual Series
2010-12-07 | E-GEOD-25883 | biostudies-arrayexpress