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The Lancet. Infectious Diseases Oct 2021
Topics: Antimalarials; Clinical Trials as Topic; Female; Humans; Infant; Malaria; Malaria Vaccines; Male; Plasmodium; Vaccination
PubMed: 34562396
DOI: 10.1016/S1473-3099(21)00569-7 -
Cold Spring Harbor Perspectives in... Aug 2017The first reference genome assembly for the malaria parasite was completed over a decade ago, and the impact of this and other genomic resources on malaria research has... (Review)
Review
The first reference genome assembly for the malaria parasite was completed over a decade ago, and the impact of this and other genomic resources on malaria research has been significant. Genomic resources for other malaria parasites are being established, even as continues to be the focus of development of new genomic methods and applications. Here we review the impact and applications of genomic data on malaria research, and discuss future needs and directions as genomic data generation becomes less expensive and more decentralized. Specifically, we focus on how population genomic strategies can be utilized to advance the malaria eradication agenda.
Topics: Animals; Anopheles; Biomedical Research; Disease Eradication; Genetic Variation; Genome, Protozoan; Genomics; Humans; Malaria; Plasmodium; Whole Genome Sequencing
PubMed: 28389516
DOI: 10.1101/cshperspect.a025544 -
Briefings in Functional Genomics Sep 2019Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained... (Review)
Review
Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host-parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host-parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.
Topics: Animals; Genomics; Host-Parasite Interactions; Humans; Plasmodium; Plasmodium cynomolgi; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium vivax; Primates; Systems Biology
PubMed: 31241151
DOI: 10.1093/bfgp/elz013 -
Trends in Parasitology Jul 2022The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and... (Review)
Review
The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the early stages of vaccine development will be critical for achieving the goal of malaria control, elimination, and ultimately eradication. Recent advances in targeted genome editing enabled the functional validation of resistance-associated markers in Plasmodium falciparum, the deadliest malaria-causing pathogen and strain-specific immune neutralization. This review explores recent advances made in leveraging genome editing to aid the functional evaluation of Plasmodium diversity and highlights how these techniques can assist in prioritizing both therapeutic and vaccine candidates.
Topics: Gene Editing; Humans; Malaria; Malaria, Falciparum; Plasmodium; Plasmodium falciparum
PubMed: 35469746
DOI: 10.1016/j.pt.2022.03.005 -
Malaria Journal May 2022Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas.... (Review)
Review
Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas. However, the origins of this parasite in this continent are still debated. Similarly, it is now accepted that the existence of Plasmodium simium is explained by a P. vivax transfer from humans to monkey in America. However, many uncertainties still exist concerning the origin of the transfer and whether several transfers occurred. In this review, the most recent studies that addressed these questions using genetic and genomic approaches are presented.
Topics: Biological Evolution; Genome; Humans; Malaria; Plasmodium; Plasmodium vivax
PubMed: 35505431
DOI: 10.1186/s12936-022-04132-7 -
Biochemical Society Transactions Apr 2024Malaria, a vector borne disease, is a major global health and socioeconomic problem caused by the apicomplexan protozoan parasite Plasmodium. The parasite alternates... (Review)
Review
Malaria, a vector borne disease, is a major global health and socioeconomic problem caused by the apicomplexan protozoan parasite Plasmodium. The parasite alternates between mosquito vector and vertebrate host, with meiosis in the mosquito and proliferative mitotic cell division in both hosts. In the canonical eukaryotic model, cell division is either by open or closed mitosis and karyokinesis is followed by cytokinesis; whereas in Plasmodium closed mitosis is not directly accompanied by concomitant cell division. Key molecular players and regulatory mechanisms of this process have been identified, but the pivotal role of certain protein complexes and the post-translational modifications that modulate their actions are still to be deciphered. Here, we discuss recent evidence for the function of known proteins in Plasmodium cell division and processes that are potential novel targets for therapeutic intervention. We also identify key questions to open new and exciting research to understand divergent Plasmodium cell division.
Topics: Plasmodium; Cell Division; Animals; Humans; Malaria; Protozoan Proteins; Mitosis; Cytokinesis; Meiosis; Protein Processing, Post-Translational; Host-Parasite Interactions
PubMed: 38563493
DOI: 10.1042/BST20230403 -
Proceedings of the National Academy of... Mar 20225-methylcytosine (mC) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological...
5-methylcytosine (mC) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if mC modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of parasites. Here, we characterize the landscape of mC mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent () and human () malaria parasites. While different representations of mC-modified mRNAs are associated with the different stages, the abundance of the mC marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that mC modifications confer stability to the transcripts and that a ortholog of NSUN2 is a major mRNA mC methyltransferase in malaria parasites. Upon knockout of (), marked reductions of mC modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the gene in the knockout parasites rescued the gametocyte production phenotype as well as mC modification of the gametocytogenesis-associated transcripts. Together with the mRNA mC profiles for two species of , our findings demonstrate a major role for NSUN2-mediated mC modifications in mRNA transcript stability and sexual differentiation in malaria parasites.
Topics: 5-Methylcytosine; Germ Cells; Plasmodium falciparum; Plasmodium yoelii; Protozoan Proteins; RNA, Messenger; Transcriptome
PubMed: 35210361
DOI: 10.1073/pnas.2110713119 -
Open Biology Dec 2017The cyclic nucleotides 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP) are intracellular messengers found in most animal... (Review)
Review
The cyclic nucleotides 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP) are intracellular messengers found in most animal cell types. They usually mediate an extracellular stimulus to drive a change in cell function through activation of their respective cyclic nucleotide-dependent protein kinases, PKA and PKG. The enzymatic components of the malaria parasite cyclic nucleotide signalling pathways have been identified, and the genetic and biochemical studies of these enzymes carried out to date are reviewed herein. What has become very clear is that cyclic nucleotides play vital roles in controlling every stage of the complex malaria parasite life cycle. Our understanding of the involvement of cyclic nucleotide signalling in orchestrating the complex biology of malaria parasites is still in its infancy, but the recent advances in our genetic tools and the increasing interest in signalling will deliver more rapid progress in the coming years.
Topics: Cyclic AMP; Cyclic GMP; Cyclic Nucleotide-Regulated Protein Kinases; Life Cycle Stages; Plasmodium; Protozoan Proteins; Signal Transduction
PubMed: 29263246
DOI: 10.1098/rsob.170213 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
The FEBS Journal May 2017Proteasomes are multisubunit, energy-dependent, proteolytic complexes that play an essential role in intracellular protein turnover. They are present in eukaryotes,... (Review)
Review
Proteasomes are multisubunit, energy-dependent, proteolytic complexes that play an essential role in intracellular protein turnover. They are present in eukaryotes, archaea, and in some actinobacteria species. Inhibition of proteasome activity has emerged as a powerful strategy for anticancer therapy and three drugs have been approved for treatment of multiple myeloma. These compounds react covalently with a threonine residue located in the active site of a proteasome subunit to block protein degradation. Proteasomes in pathogenic organisms such as Mycobacterium tuberculosis and Plasmodium falciparum also have a nucleophilic threonine residue in the proteasome active site and are therefore sensitive to these anticancer drugs. This review summarizes efforts to validate the proteasome in pathogenic organisms as a therapeutic target. We describe several strategies that have been used to develop inhibitors with increased potency and selectivity for the pathogen proteasome relative to the human proteasome. In addition, we highlight a cell-based chemical screening approach that identified a potent, allosteric inhibitor of proteasomes found in Leishmania and Trypanosoma species. Finally, we discuss the development of proteasome inhibitors as anti-infective agents.
Topics: Animals; Anti-Infective Agents; Humans; Mycobacterium; Plasmodium; Proteasome Endopeptidase Complex; Schistosoma
PubMed: 28122162
DOI: 10.1111/febs.14029