Additional file 6 : Table S2. ΔACL/iΔACS acetytlome. Excel spreadheet summarising the acetylome data set from the nanoLC-MS/MS analysis. Sites and proteins which are significantly hypo- or hyper-acetylated in ΔACL/iΔACS parasites are highlighted. Abbreviations: ACL: ATP-citrate lyase; ACS: acetyl-CoA synthetase; LC-MS/MS: liquid chromatography-tandem mass spectrometry.
The datasets here are a key addition to the Malaria Cell Atlas, that include short and long read single cell RNA-sequencing profiles of i) over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development of laboratory strains ii) ~1000 P. falciparum parasites collected from an asymptomatic Malian individual naturally infected with multiple strains. A single cell atlas comprising the laboratory dataset as well as an integrated atlas of both laboratory and field strains is generated and provided as a data resource to the malaria research community at malariacellatlas.org
The datasets here are a key addition to the Malaria Cell Atlas, that include short and long read single cell RNA-sequencing profiles of i) over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development of laboratory strains ii) ~8000 P. falciparum parasites collected from four asymptomatic Malian individuals naturally infected with multiple strains. A single cell atlas comprising the laboratory dataset as well as an integrated atlas of both laboratory and field strains is generated and provided as a data resource to the malaria research community at malariacellatlas.org
The developmental decision made by malaria parasites to become sexual underlies all malaria transmission. Here, we describe a rich atlas of short- and long-read single-cell transcriptomes of over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development. We used the atlas to explore transcriptional modules and exon usage along sexual development and expanded it to include malaria parasites collected from four Malian individuals naturally infected with multiple P. falciparum strains. We investigated genotypic and transcriptional heterogeneity within and among these wild strains at the single-cell level, finding differential expression between different strains even within the same host. These data are a key addition to the Malaria Cell Atlas interactive data resource, enabling a deeper understanding of the biology and diversity of transmission stages.
Abstract Background Acetyl-CoA is a key molecule in all organisms, implicated in several metabolic pathways as well as in transcriptional regulation and post-translational modification. The human pathogen Toxoplasma gondii possesses at least four enzymes which generate acetyl-CoA in the nucleo-cytosol (acetyl-CoA synthetase (ACS); ATP citrate lyase (ACL)), mitochondrion (branched-chain α-keto acid dehydrogenase-complex (BCKDH)) and apicoplast (pyruvate dehydrogenase complex (PDH)). Given the diverse functions of acetyl-CoA, we know very little about the role of sub-cellular acetyl-CoA pools in parasite physiology. Results To assess the importance and functions of sub-cellular acetyl-CoA-pools, we measured the acetylome, transcriptome, proteome and metabolome of parasites lacking ACL/ACS or BCKDH. We demonstrate that ACL/ACS constitute a synthetic lethal pair. Loss of both enzymes causes a halt in fatty acid elongation, hypo-acetylation of nucleo-cytosolic and secretory proteins and broad changes in gene expression. In contrast, loss of BCKDH results in an altered TCA cycle, hypo-acetylation of mitochondrial proteins and few specific changes in gene expression. We provide evidence that changes in the acetylome, transcriptome and proteome of cells lacking BCKDH enable the metabolic adaptations and thus the survival of these parasites. Conclusions Using multi-omics and molecular tools, we obtain a global and integrative picture of the role of distinct acetyl-CoA pools in T. gondii physiology. Cytosolic acetyl-CoA is essential and is required for the synthesis of parasite-specific fatty acids. In contrast, loss of mitochondrial acetyl-CoA can be compensated for through metabolic adaptations implemented at the transcriptional, translational and post-translational level.
Additional file 10 : Table S5. ΔACL/iΔACS proteome. Excel spreadheet summarising the proteome data set from the nano-LC-MS/MS analysis. Proteins which are significantly up- or downregulated in ΔACL/iΔACS parasites are highlighted. Abbreviations: ACL: ATP-citrate lyase; ACS: acetyl-CoA synthetase; LC-MS/MS: liquid chromatography-tandem mass spectrometry.
Abstract Malaria parasites have a complex life cycle featuring diverse developmental strategies, each uniquely adapted to navigate specific host environments. Here we use single-cell transcriptomics to illuminate gene usage across the transmission cycle of the most virulent agent of human malaria – Plasmodium falciparum . We reveal developmental trajectories associated with the colonisation of the mosquito midgut and salivary glands and elucidate the transcriptional signatures of each transmissible stage. Additionally, we identify both conserved and nonconserved gene usage between human and rodent parasites, which point to both essential mechanisms in malaria transmission and species-specific adaptations potentially linked to host tropism. Together, the data presented here, which are made freely available via an interactive website, establish the most complete atlas of the P. falciparum transcriptional journey to date. One sentence summary Single-cell transcriptomics of P. falciparum transmission stages highlights developmental trajectories and gene usage.
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