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Trends in Parasitology Jul 2018Malaria is a serious, complex disease caused by parasites of the genus Plasmodium. Plasmodium parasites affect multiple tissues as they evade immune responses,... (Review)
Review
Malaria is a serious, complex disease caused by parasites of the genus Plasmodium. Plasmodium parasites affect multiple tissues as they evade immune responses, replicate, sexually reproduce, and transmit between vertebrate and invertebrate hosts. The explosion of omics technologies has enabled large-scale collection of Plasmodium infection data, revealing systems-scale patterns, mechanisms of pathogenesis, and the ways that host and pathogen affect each other. Here, we provide an overview of recent efforts using systems biology approaches to study host-Plasmodium interactions and the biological themes that have emerged from these efforts. We discuss some of the challenges in using systems biology for this goal, key research efforts needed to address those issues, and promising future malaria applications of systems biology.
Topics: Animals; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Systems Biology
PubMed: 29779985
DOI: 10.1016/j.pt.2018.04.003 -
Parasites & Vectors Dec 2022The production of Plasmodium gametocytes in vitro is a real challenge. Many protocols have been described, but few have resulted in the production of viable and... (Review)
Review
BACKGROUND
The production of Plasmodium gametocytes in vitro is a real challenge. Many protocols have been described, but few have resulted in the production of viable and infectious gametocytes in sufficient quantities to conduct research on-but not limited to-transmission-blocking drug and vaccine development. The aim of this review was to identify and discuss gametocyte production protocols that have been developed over the last two decades.
METHODS
We analyzed the original gametocyte production protocols published from 2000 onwards based on a literature search and a thorough review. A systematic review was performed of relevant articles identified in the PubMed, Web of Sciences and ScienceDirect databases.
RESULTS
A total 23 studies on the production of Plasmodium gametocytes were identified, 19 involving in vitro Plasmodium falciparum, one involving Plasmodium knowlesi and three involving ex vivo Plasmodium vivax. Of the in vitro studies, 90% used environmental stressors to trigger gametocytogenesis. Mature gametocytemia of up to 4% was reported.
CONCLUSIONS
Several biological parameters contribute to an optimal production in vitro of viable and infectious mature gametocytes. The knowledge gained from this systematic review on the molecular mechanisms involved in gametocytogenesis enables reproducible gametocyte protocols with transgenic parasite lines to be set up. This review highlights the need for additional gametocyte production protocols for Plasmodium species other than P. falciparum.
Topics: Humans; Malaria, Falciparum; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium vivax; Systematic Reviews as Topic
PubMed: 36471426
DOI: 10.1186/s13071-022-05566-3 -
PLoS Pathogens Apr 2023
Topics: Animals; Parasites; Plasmodium; Ribosomes
PubMed: 37053161
DOI: 10.1371/journal.ppat.1011267 -
Genetics Aug 2019Understanding the relatedness of individuals within or between populations is a common goal in biology. Increasingly, relatedness features in genetic epidemiology...
Understanding the relatedness of individuals within or between populations is a common goal in biology. Increasingly, relatedness features in genetic epidemiology studies of pathogens. These studies are relatively new compared to those in humans and other organisms, but are important for designing interventions and understanding pathogen transmission. Only recently have researchers begun to routinely apply relatedness to apicomplexan eukaryotic malaria parasites, and to date have used a range of different approaches on an basis. Therefore, it remains unclear how to compare different studies and which measures to use. Here, we systematically compare measures based on identity-by-state (IBS) and identity-by-descent (IBD) using a globally diverse data set of malaria parasites, and , and provide marker requirements for estimates based on IBD. We formally show that the informativeness of polyallelic markers for relatedness inference is maximized when alleles are equifrequent. Estimates based on IBS are sensitive to allele frequencies, which vary across populations and by experimental design. For portability across studies, we thus recommend estimates based on IBD. To generate estimates with errors below an arbitrary threshold of 0.1, we recommend ∼100 polyallelic or 200 biallelic markers. Marker requirements are immediately applicable to haploid malaria parasites and other haploid eukaryotes. C.I.s facilitate comparison when different marker sets are used. This is the first attempt to provide rigorous analysis of the reliability of, and requirements for, relatedness inference in malaria genetic epidemiology. We hope it will provide a basis for statistically informed prospective study design and surveillance strategies.
Topics: Genome, Protozoan; Models, Genetic; Pedigree; Phylogeny; Plasmodium falciparum; Plasmodium vivax; Polymorphism, Single Nucleotide
PubMed: 31209105
DOI: 10.1534/genetics.119.302120 -
BMC Microbiology Mar 2022Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for...
BACKGROUND
Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for the development of an effective vaccine. The aim of the current study was a comprehensive analysis of the experimentally validated epitopes of Plasmodium obtained from various immunoassays.
METHODS
Plasmodium species epitopes were prefetched from Immune Epitope Database (IEDB). Species specific classification of available epitopes was done for both human and murine malaria parasites. Further, these T cell and B cell epitopes along with MHC I/II binders of different Plasmodium species were examined to find out their capability to induce IFN-γ and IL-10 using IFNepitope and IL-10 Pred, respectively.
RESULTS
The species-specific classification of 6874 unique epitopes resulted in the selection of predominant human and murine Plasmodium species. Further, the attempt was made to analyse the immune reactivity of these epitopes for their ability to induce cytokines namely IFN-γ and IL-10. Total, 2775 epitopes were predicted to possess IFN-γ inducing ability, whereas 1275 epitopes were found to be involved in the induction of IL-10.
CONCLUSIONS
This study facilitates the assessment of Plasmodium epitopes and associated proteins as a potential approach to design and develop an epitope-based vaccine. Moreover, the results highlight the epitope-based immunization in malaria to induce a protective immune response.
Topics: Animals; Antigens, Protozoan; Epitopes, T-Lymphocyte; Humans; Interleukin-10; Malaria; Mice; Plasmodium; Plasmodium falciparum; Protozoan Proteins
PubMed: 35277125
DOI: 10.1186/s12866-022-02480-7 -
Frontiers in Cellular and Infection... 2020Autoantibodies are frequently reported in patients with malaria, but whether they contribute to protection or to pathology is an issue of debate. A large body of... (Review)
Review
Autoantibodies are frequently reported in patients with malaria, but whether they contribute to protection or to pathology is an issue of debate. A large body of evidence indicates that antibodies against host-self components are associated to malaria clinical outcomes such as cerebral malaria, renal dysfunction and anemia. Nonetheless, self-reactive immunoglobulins induced during an infection can also mediate protection. In light of these controversies, we summarize here the latest findings in our understanding of autoimmune responses in malaria, focusing on and . We review the main targets of self-antibody responses in malaria as well as the current, but still limited, knowledge of their role in disease pathogenesis or protection.
Topics: Autoantibodies; Humans; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax
PubMed: 32596165
DOI: 10.3389/fcimb.2020.00262 -
Parasitology Apr 2020Factors such as the particular combination of parasite-mosquito species, their co-evolutionary history and the host's parasite load greatly affect parasite transmission....
Factors such as the particular combination of parasite-mosquito species, their co-evolutionary history and the host's parasite load greatly affect parasite transmission. However, the importance of these factors in the epidemiology of mosquito-borne parasites, such as avian malaria parasites, is largely unknown. Here, we assessed the competence of two mosquito species [Culex pipiens and Aedes (Ochlerotatus) caspius], for the transmission of four avian Plasmodium lineages (Plasmodium relictum SGS1 and GRW11 and Plasmodium cathemerium-related lineages COLL1 and PADOM01) naturally infecting wild house sparrows. We assessed the effects of parasite identity and parasite load on Plasmodium transmission risk through its effects on the transmission rate and mosquito survival. We found that Cx. pipiens was able to transmit the four Plasmodium lineages, while Ae. caspius was unable to transmit any of them. However, Cx. pipiens mosquitoes fed on birds infected by P. relictum showed a lower survival and transmission rate than those fed on birds infected by parasites related to P. cathemerium. Non-significant associations were found with the host-parasite load. Our results confirm the existence of inter- and intra-specific differences in the ability of Plasmodium lineages to develop in mosquito species and their effects on the survival of mosquitoes that result in important differences in the transmission risk of the different avian malaria parasite lineages studied.
Topics: Aedes; Animals; Culex; Female; Malaria, Avian; Male; Mosquito Vectors; Ochlerotatus; Plasmodium; Spain; Sparrows; Species Specificity
PubMed: 31965951
DOI: 10.1017/S0031182020000062 -
Current Opinion in Hematology May 2016Red cell receptors provide unique entry points for Plasmodium parasites to initiate blood-stage malaria infection. Parasites encode distinct ligands that bind... (Review)
Review
PURPOSE OF REVIEW
Red cell receptors provide unique entry points for Plasmodium parasites to initiate blood-stage malaria infection. Parasites encode distinct ligands that bind specifically to both highly abundant and low-copy receptors. Recent advances in the understanding of molecular and structural mechanisms of these interactions provide fundamental insights into receptor-ligand biology and molecular targets for intervention.
RECENT FINDINGS
The review focuses on the requirements for known interactions, insight derived from complex structures, and mechanisms of receptor/ligand engagement. Further, novel roles for established red cell membrane proteins, parasite ligands and associated interacting partners have recently been established in red cell invasion.
SUMMARY
The new knowledge underlines the intricacies involved in invasion by a eukaryotic parasite into a eukaryotic host cell demonstrated by expanded parasite ligand families, redundancy in red cell receptor engagement, multitiered temporal binding, and the breadth of receptors engaged.
Topics: Erythrocytes; Host-Parasite Interactions; Humans; Ligands; Malaria; Plasmodium; Receptors, Cell Surface
PubMed: 26766537
DOI: 10.1097/MOH.0000000000000219 -
The Biochemical Journal Jul 2021During malarial infection, Plasmodium parasites digest human hemoglobin to obtain free amino acids for protein production and maintenance of osmotic pressure. The...
During malarial infection, Plasmodium parasites digest human hemoglobin to obtain free amino acids for protein production and maintenance of osmotic pressure. The Plasmodium M1 and M17 aminopeptidases are both postulated to have an essential role in the terminal stages of the hemoglobin digestion process and are validated drug targets for the design of new dual-target anti-malarial compounds. In this study, we profiled the substrate specificity fingerprints and kinetic behaviors of M1 and M17 aminopeptidases from Plasmodium falciparum and Plasmodium vivax, and the mouse model species, Plasmodium berghei. We found that although the Plasmodium M1 aminopeptidases share a largely similar, broad specificity at the P1 position, the P. falciparum M1 displays the greatest diversity in specificity and P. berghei M1 showing a preference for charged P1 residues. In contrast, the Plasmodium M17 aminopeptidases share a highly conserved preference for hydrophobic residues at the P1 position. The aminopeptidases also demonstrated intra-peptide sequence specificity, particularly the M1 aminopeptidases, which showed a definitive preference for peptides with fewer negatively charged intrapeptide residues. Overall, the P. vivax and P. berghei enzymes had a faster substrate turnover rate than the P. falciparum enzymes, which we postulate is due to subtle differences in structural dynamicity. Together, these results build a kinetic profile that allows us to better understand the catalytic nuances of the M1 and M17 aminopeptidases from different Plasmodium species.
Topics: Aminopeptidases; Animals; Biocatalysis; Humans; Isoenzymes; Kinetics; Leucine; Malaria; Mice; Peptides; Plasmodium; Plasmodium berghei; Plasmodium falciparum; Plasmodium vivax; Protease Inhibitors; Protozoan Proteins; Recombinant Proteins; Species Specificity; Substrate Specificity
PubMed: 34133730
DOI: 10.1042/BCJ20210172 -
FEMS Microbiology Reviews May 2018Recent years have witnessed a great gain in knowledge regarding parasite-host cell interactions during Plasmodium liver stage development. It is now an accepted fact... (Review)
Review
Recent years have witnessed a great gain in knowledge regarding parasite-host cell interactions during Plasmodium liver stage development. It is now an accepted fact that a large percentage of sporozoites invading hepatocytes fail to form infectious merozoites. There appears to be a delicate balance between parasite survival and elimination and we now start to understand why this is so. Plasmodium liver stage parasites replicate within the parasitophorous vacuole (PV), formed during invasion by invagination of the host cell plasma membrane. The main interface between the parasite and hepatocyte is the parasitophorous vacuole membrane (PVM) that surrounds the PV. Recently, it was shown that autophagy marker proteins decorate the PVM of Plasmodium liver stage parasites and eliminate a proportion of them by an autophagy-like mechanism. Successfully developing Plasmodium berghei parasites are initially also labeled but in the course of development, they are able to control this host defense mechanism by shedding PVM material into the tubovesicular network (TVN), an extension of the PVM that releases vesicles into the host cell cytoplasm. Better understanding of the molecular events at the PVM/TVN during parasite elimination could be the basis of new antimalarial measures.
Topics: Animals; Cytosol; Hepatocytes; Host-Parasite Interactions; Humans; Life Cycle Stages; Liver; Plasmodium
PubMed: 29529207
DOI: 10.1093/femsre/fuy007