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Genes May 2021Genomics has revolutionised the study of the biology of parasitic diseases. The first Eukaryotic parasite to have its genome sequenced was the malaria parasite . Since... (Review)
Review
Genomics has revolutionised the study of the biology of parasitic diseases. The first Eukaryotic parasite to have its genome sequenced was the malaria parasite . Since then, genomics has continued to lead the way in the study of the genome biology of parasites, both in breadth-the number of species' genomes sequenced-and in depth-massive-scale genome re-sequencing of several key species. Here, we review some of the insights into the biology, evolution and population genetics of gained from genome sequencing, and look at potential new avenues in the future genome-scale study of its biology.
Topics: Epigenome; Genome, Protozoan; Humans; Malaria; Plasmodium falciparum; Polymorphism, Genetic
PubMed: 34070769
DOI: 10.3390/genes12060843 -
Malaria Journal Feb 2016Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to... (Review)
Review
Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.
Topics: Angola; Antimalarials; Drug Resistance; Humans; Malaria, Falciparum; Plasmodium falciparum
PubMed: 26858018
DOI: 10.1186/s12936-016-1122-z -
Malaria Journal Oct 2015Glycoconjugates are important mediators of host-pathogen interactions and are usually very abundant in the surface of many protozoan parasites. However, in the... (Review)
Review
Glycoconjugates are important mediators of host-pathogen interactions and are usually very abundant in the surface of many protozoan parasites. However, in the particular case of Plasmodium species, previous works show that glycosylphosphatidylinositol anchor modifications, and to an unknown extent, a severely truncated N-glycosylation are the only glycosylation processes taking place in the parasite. Nevertheless, a detailed analysis of the parasite genome and the recent identification of the sugar nucleotide precursors biosynthesized by Plasmodium falciparum support a picture in which several overlooked, albeit not very prominent glycosylations may be occurring during the parasite life cycle. In this work, the authors review recent developments in the characterization of the biosynthesis of glycosylation precursors in the parasite, focusing on the outline of the possible fates of these precursors.
Topics: Carbohydrate Metabolism; Glycosylation; Metabolic Networks and Pathways; Plasmodium falciparum
PubMed: 26520586
DOI: 10.1186/s12936-015-0949-z -
Frontiers in Cellular and Infection... 2018Malaria, a disease caused by parasites, is widespread throughout tropical and sub-tropical regions worldwide; it mostly affects children and pregnant woman. Eradication... (Review)
Review
Malaria, a disease caused by parasites, is widespread throughout tropical and sub-tropical regions worldwide; it mostly affects children and pregnant woman. Eradication has stalled despite effective prevention measures and medication being available for this disease; this has mainly been due to the parasite's resistance to medical treatment and the mosquito vector's resistance to insecticides. Tackling such resistance involves using renewed approaches and techniques for accruing a deep understanding of the parasite's biology, and developing new drugs and vaccines. Studying the parasite's invasion of erythrocytes should shed light on its ability to switch between invasion phenotypes related to the expression of gene sets encoding proteins acting as ligands during target cell invasion, thereby conferring mechanisms for evading a particular host's immune response and adapting to changes in target cell surface receptors. This review considers some factors influencing the expression of such phenotypes, such as 's genetic, transcriptional and epigenetic characteristics, and explores some host-related aspects which could affect parasite phenotypes, aiming at integrating knowledge regarding this topic and the possible relationship between the parasite's biology and host factors playing a role in erythrocyte invasion.
Topics: Endocytosis; Erythrocytes; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Plasmodium falciparum
PubMed: 30693273
DOI: 10.3389/fcimb.2018.00454 -
Molecular Microbiology May 2021Malaria is one of the most life-threatening infectious diseases worldwide, caused by infection of humans with parasites of the genus Plasmodium. The complex life cycle... (Review)
Review
Malaria is one of the most life-threatening infectious diseases worldwide, caused by infection of humans with parasites of the genus Plasmodium. The complex life cycle of Plasmodium parasites is shared between two hosts, with infection of multiple cell types, and the parasite needs to adapt for survival and transmission through significantly different metabolic environments. Within the blood-stage alone, parasites encounter changing levels of key nutrients, including sugars, amino acids, and lipids, due to differences in host dietary nutrition, cellular tropism, and pathogenesis. In this review, we consider the mechanisms that the most lethal of malaria parasites, Plasmodium falciparum, uses to sense nutrient levels and elicit changes in gene expression during blood-stage infections. These changes are brought about by several metabolic intermediates and their corresponding sensor proteins. Sensing of distinct nutritional signals can drive P. falciparum to alter the key blood-stage processes of proliferation, antigenic variation, and transmission.
Topics: Animals; Gene Expression; Humans; Life Cycle Stages; Malaria, Falciparum; Nutrients; Plasmodium falciparum
PubMed: 33236377
DOI: 10.1111/mmi.14652 -
Malaria Journal Mar 2019While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the... (Review)
Review
While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the gametocyte sex ratio contribution to this process still remains a relevant research question. The present review discusses the biology of sex determination in P. falciparum, the underlying host and parasite factors, the sex specific susceptibility to drugs, the effect of sex ratio dynamics on malaria parasite transmission and the development of gametocyte sex specific diagnosis tools. Despite the inherent differences across several studies and approaches, the emerging picture highlights a potentially relevant contribution of the P. falciparum gametocyte sex ratio in the modulation of malaria parasite transmission. The increasing availability of molecular methods to measure gametocyte sex ratio will enable evaluation of important parameters, such as the impact of drug treatment on gametocyte sex ratio in vitro and in vivo as well as the changes of gametocyte sex ratios in natural infections, key steps towards elucidating how these parameters affect parasite infectiousness to the mosquito vectors.
Topics: Disease Transmission, Infectious; Female; Genotype; Humans; Malaria, Falciparum; Male; Phenotype; Plasmodium falciparum
PubMed: 30866941
DOI: 10.1186/s12936-019-2707-0 -
MSphere Aug 2023Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in...
Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the orthologs of two core NMD components: UPF1 (PF3D7_1005500) and UPF2 (PF3D7_0925800). We localize both UPF1 and UPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in , they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in has no functional role and that NMD is not required for parasite growth . IMPORTANCE In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.
Topics: Humans; Plasmodium falciparum; Nonsense Mediated mRNA Decay; Gene Expression Regulation; RNA, Messenger; Malaria
PubMed: 37366629
DOI: 10.1128/msphere.00233-23 -
Molecular and Biochemical Parasitology Aug 2010Male and female gametocytes are the components of the malaria parasite life cycle which are taken up from an infected host bloodstream by mosquitoes and thus mediate... (Review)
Review
Male and female gametocytes are the components of the malaria parasite life cycle which are taken up from an infected host bloodstream by mosquitoes and thus mediate disease transmission. These gamete precursors are morphologically and functionally quite distinct from their asexual blood stage counterparts and this is reflected in their distinct patterns of gene expression, cellular development and metabolism. Recent transcriptome, proteome and reverse genetic studies have added valuable information to that obtained from traditional studies. However, we still have no answer to the fundamental question regarding sexual development: 'what triggers gametocytogenesis'? In the current climate of eradication/elimination, tackling transmission by killing gametocytes has an important place on the agenda because most antimalarial drugs, whilst killing asexual blood stage parasites, have no effect on the transmissible stages.
Topics: Animals; Gene Expression Profiling; Gene Expression Regulation; Genetic Engineering; Genetics, Microbial; Life Cycle Stages; Plasmodium falciparum; Proteome
PubMed: 20381542
DOI: 10.1016/j.molbiopara.2010.03.019 -
Frontiers in Immunology 2019Malaria infections remain a serious global health problem in the world, particularly among children and pregnant women in Sub-Saharan Africa. Moreover, malaria control... (Review)
Review
Malaria infections remain a serious global health problem in the world, particularly among children and pregnant women in Sub-Saharan Africa. Moreover, malaria control and elimination is hampered by rapid development of resistance by the parasite and the vector to commonly used antimalarial drugs and insecticides, respectively. Therefore, vaccine-based strategies are sorely needed, including those designed to interrupt disease transmission. However, a prerequisite for such a vaccine strategy is the understanding of both the human and vector immune responses to parasite developmental stages involved in parasite transmission in both man and mosquito. Here, we review the naturally acquired humoral and cellular responses to sexual stages of the parasite while in the human host and the vector. In addition, updates on current anti-gametocyte, anti-gamete, and anti-mosquito transmission blocking vaccines are given. We conclude with our views on some important future directions of research into sexual stage immunity relevant to the search for the most appropriate transmission-blocking vaccine.
Topics: Animals; Antigens, Protozoan; Host-Parasite Interactions; Humans; Life Cycle Stages; Malaria Vaccines; Mosquito Vectors; Plasmodium falciparum
PubMed: 30804940
DOI: 10.3389/fimmu.2019.00136 -
Current Opinion in Microbiology Dec 2020For malaria parasites regulating sexual commitment, the frequency with which asexual bloodstream forms differentiate into non-replicative male and female gametocytes, is... (Review)
Review
For malaria parasites regulating sexual commitment, the frequency with which asexual bloodstream forms differentiate into non-replicative male and female gametocytes, is critical because asexual replication is required to maintain a persistent infection of the human host while gametocytes are essential for infection of the mosquito vector and transmission. Here, we describe recent advances in understanding of the regulatory mechanisms controlling this key developmental decision. These include new insights into the mechanistic roles of the transcriptional master switch AP2-G and the epigenetic modulator GDV1, as well as the identification of defined metabolic signals that modulate their activity. Many of these metabolites are linked to parasite phospholipid biogenesis and we propose a model linking this pathway to the epigenetic regulation underlying sexual commitment in P. falciparum.
Topics: Animals; Epigenesis, Genetic; Germ Cells; Humans; Malaria, Falciparum; Plasmodium falciparum; Reproduction
PubMed: 33053503
DOI: 10.1016/j.mib.2020.09.004