Commit, hide and escape: the story ofPlasmodiumgametocytes

Parasitology ◽  
2018 ◽  
Vol 145 (13) ◽  
pp. 1772-1782 ◽  
Author(s):  
Divya Beri ◽  
Balu Balan ◽  
Utpal Tatu
Keyword(s):  
Life Cycle ◽  
Causative Agent ◽  
Malaria Elimination ◽  
Molecular Mechanisms ◽  
Modern Technology ◽  
Vital Role ◽  
Complex Life Cycle ◽  
Sexual Stage ◽  
Mortality And Morbidity ◽  
Human Host

AbstractMalaria is the major cause of mortality and morbidity in tropical countries. The causative agent,Plasmodiumsp., has a complex life cycle and is armed with various mechanisms which ensure its continuous transmission. Gametocytes represent the sexual stage of the parasite and are indispensable for the transmission of the parasite from the human host to the mosquito. Despite its vital role in the parasite's success, it is the least understood stage in the parasite's life cycle. The presence of gametocytes in asymptomatic populations and induction of gametocytogenesis by most antimalarial drugs warrants further investigation into its biology. With a renewed focus on malaria elimination and advent of modern technology available to biologists today, the field of gametocyte biology has developed swiftly, providing crucial insights into the molecular mechanisms driving sexual commitment. This review will summarise key current findings in the field of gametocyte biology and address the associated challenges faced in malaria detection, control and elimination.

scholarly journals Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies

2021 ◽  
Vol 17 (4) ◽  
pp. e1008067
Author(s):  
Lisette Meerstein-Kessel ◽  
Jeron Venhuizen ◽  
Daniel Garza ◽  
Nicholas I. Proellochs ◽  
Emma J. Vos ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Salivary Glands ◽  
Molecular Mechanisms ◽  
Life Stage ◽  
Acid Synthesis ◽  
Complex Life Cycle ◽  
Quiescent State ◽  
Extended Phase ◽  
Human Host ◽  
Falciparum Sporozoite

Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and proteomics studies and is also targeted by the most advanced malaria vaccine. We applied Bayesian data integration to determine which proteins are not only present in sporozoites but are also specific to that stage. Transcriptomic and proteomic Plasmodium data sets from 26 studies were weighted for how representative they are for sporozoites, based on a carefully assembled gold standard for Plasmodium falciparum (Pf) proteins known to be present or absent during the sporozoite life stage. Of 5418 Pf genes for which expression data were available at the RNA level or at the protein level, 975 were identified as enriched in sporozoites and 90 specific to them. We show that Pf sporozoites are enriched for proteins involved in type II fatty acid synthesis in the apicoplast and GPI anchor synthesis, but otherwise appear metabolically relatively inactive in the salivary glands of mosquitos. Newly annotated hypothetical sporozoite-specific and sporozoite-enriched proteins highlight sporozoite-specific functions. They include PF3D7_0104100 that we identified to be homologous to the prominin family, which in human has been related to a quiescent state of cancer cells. We document high levels of genetic variability for sporozoite proteins, specifically for sporozoite-specific proteins that elicit antibodies in the human host. Nevertheless, we can identify nine relatively well-conserved sporozoite proteins that elicit antibodies and that together can serve as markers for previous exposure. Our understanding of sporozoite biology benefits from identifying key pathways that are enriched during this life stage. This work can guide studies of molecular mechanisms underlying sporozoite biology and potential well-conserved targets for marker and drug development.

scholarly journals Malaria Parasite Stress Tolerance Is Regulated by DNMT2-Mediated tRNA Cytosine Methylation

mBio ◽  
2021 ◽  
Author(s):  
Elie Hammam ◽  
Ameya Sinha ◽  
Sebastian Baumgarten ◽  
Flore Nardella ◽  
Jiaqi Liang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Malaria Parasite ◽  
Cytosine Methylation ◽  
Parasite Species ◽  
Environmental Stressors ◽  
Complex Life Cycle ◽  
Content Type ◽  
Mortality And Morbidity ◽  
Disease Mortality ◽  
New Strategies

P. falciparum is the most virulent malaria parasite species, accounting for the majority of the disease mortality and morbidity. Understanding how this pathogen is able to adapt to different cellular and environmental stressors during its complex life cycle is crucial in order to develop new strategies to tackle the disease.

scholarly journals Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Daffiny Sumam de Oliveira ◽  
Thales Kronenberger ◽  
Giuseppe Palmisano ◽  
Carsten Wrenger ◽  
Edmarcia Elisa de Souza
Keyword(s):  
Life Cycle ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Public Health Problem ◽  
Complex Life Cycle ◽  
Cellular Functions ◽  
Cellular Mechanisms ◽  
Malaria Parasites ◽  
Malaria Therapy ◽  
Lysine Residues

Malaria is a parasitic disease that represents a public health problem worldwide. Protozoans of the Plasmodium genus are responsible for causing malaria in humans. Plasmodium species have a complex life cycle that requires post-translational modifications (PTMs) to control cellular activities temporally and spatially and regulate the levels of critical proteins and cellular mechanisms for maintaining an efficient infection and immune evasion. SUMOylation is a PTM formed by the covalent linkage of a small ubiquitin-like modifier protein to the lysine residues on the protein substrate. This PTM is reversible and is triggered by the sequential action of three enzymes: E1-activating, E2-conjugating, and E3 ligase. On the other end, ubiquitin-like-protein-specific proteases in yeast and sentrin-specific proteases in mammals are responsible for processing SUMO peptides and for deconjugating SUMOylated moieties. Further studies are necessary to comprehend the molecular mechanisms and cellular functions of SUMO in Plasmodium. The emergence of drug-resistant malaria parasites prompts the discovery of new targets and antimalarial drugs with novel mechanisms of action. In this scenario, the conserved biological processes regulated by SUMOylation in the malaria parasites such as gene expression regulation, oxidative stress response, ubiquitylation, and proteasome pathways, suggest PfSUMO as a new potential drug target. This mini-review focuses on the current understanding of the mechanism of action of the PfSUMO during the coordinated multi-step life cycle of Plasmodium and discusses them as attractive new target proteins for the development of parasite-specific inhibitors and therapeutic intervention toward malaria disease.

scholarly journals Malaria parasite egress at a glance

2021 ◽  
Vol 134 (5) ◽  
pp. jcs257345
Author(s):  
Michele S. Y Tan ◽  
Michael J. Blackman
Keyword(s):  
Life Cycle ◽  
Malaria Control ◽  
Cyst Wall ◽  
Malaria Parasite ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Complex Life Cycle ◽  
Intracellular Pathogens ◽  
Parasite Egress ◽  
Intracellular Vacuole

ABSTRACTAll intracellular pathogens must escape (egress) from the confines of their host cell to disseminate and proliferate. The malaria parasite only replicates in an intracellular vacuole or in a cyst, and must undergo egress at four distinct phases during its complex life cycle, each time disrupting, in a highly regulated manner, the membranes or cyst wall that entrap the parasites. This Cell Science at a Glance article and accompanying poster summarises our current knowledge of the morphological features of egress across the Plasmodium life cycle, the molecular mechanisms that govern the process, and how researchers are working to exploit this knowledge to develop much-needed new approaches to malaria control.

scholarly journals Emerging paramyxoviruses: molecular mechanisms and antiviral strategies

2011 ◽  
Vol 13 ◽  
Author(s):  
Hector C. Aguilar ◽  
Benhur Lee
Keyword(s):  
Life Cycle ◽  
High Mortality ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Human Metapneumovirus ◽  
Avian Paramyxovirus ◽  
Entry And Exit ◽  
Mortality And Morbidity ◽  
Recent Emergence

In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this family) were first identified in the 1990s in Australia, Malaysia and Singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. Other paramyxoviruses, such as Menangle virus, Tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.

Ultrastructural analysis of “Sensory” surface nerve endings and “putative” neurotransmitter sites in Schistosoma mansoni Miracidia

1989 ◽  
Vol 47 ◽  
pp. 962-963
Author(s):  
Betty Ruth Jones ◽  
Steve Chi-Tang Pan
Keyword(s):  
Nervous System ◽  
Life Cycle ◽  
Schistosoma Mansoni ◽  
Snail Host ◽  
Complex Life Cycle ◽  
Rational Approach ◽  
Effective Control ◽  
The Social ◽  
Social And Economic Development ◽  
Basic Biology

INTRODUCTION: Schistosomiasis has been described as “one of the most devastating diseases of mankind, second only to malaria in its deleterious effects on the social and economic development of populations in many warm areas of the world.” The disease is worldwide and is probably spreading faster and becoming more intense than the overall research efforts designed to provide the basis for countering it. Moreover, there are indications that the development of water resources and the demands for increasing cultivation and food in developing countries may prevent adequate control of the disease and thus the number of infections are increasing.Our knowledge of the basic biology of the parasites causing the disease is far from adequate. Such knowledge is essential if we are to develop a rational approach to the effective control of human schistosomiasis. The miracidium is the first infective stage in the complex life cycle of schistosomes. The future of the entire life cycle depends on the capacity and ability of this organism to locate and enter a suitable snail host for further development, Little is known about the nervous system of the miracidium of Schistosoma mansoni and of other trematodes. Studies indicate that miracidia contain a well developed and complex nervous system that may aid the larvae in locating and entering a susceptible snail host (Wilson, 1970; Brooker, 1972; Chernin, 1974; Pan, 1980; Mehlhorn, 1988; and Jones, 1987-1988).

Antennal transcriptome analysis and candidate olfactory genes in Crematogaster rogenhoferi

2021 ◽  
pp. 1-12
Author(s):  
Xiang Zhou ◽  
Jixing Guo ◽  
Mingxia Zhang ◽  
Chunxiu Bai ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Biological Control ◽  
Transcriptome Analysis ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Biological Control Agent ◽  
Control Agent ◽  
Vital Role ◽  
Neuron Membrane ◽  
Ionotropic Receptors ◽  
Soft Scale

Abstract Crematogaster rogenhoferi (Hymenoptera: Formicidae), an omnivorous ant, is one of the dominant predatory natural enemies of a soft scale pest, Parasaissetia nigra Nietner (Homoptera: Coccidae), and can effectively control P. nigra populations in rubber forests. Olfaction plays a vital role in the process of predation. However, the information about the molecular mechanism of olfaction-evoked behaviour in C. rogenhoferi is limited. In this study, we conducted antennal transcriptome analysis to identify candidate olfactory genes. We obtained 53,892 unigenes, 16,185 of which were annotated. Based on annotations, we identified 49 unigenes related to chemoreception, including four odourant-binding proteins, three chemosensory proteins, 37 odourant receptors, two odourant ionotropic receptors and three sensory neuron membrane proteins. This is the first report on the molecular basis of the chemosensory system of C. rogenhoferi. The findings provide a basis for elucidating the molecular mechanisms of the olfactory-related behaviours of C. rogenhoferi, which would facilitate a better application of C. rogenhoferi as a biological control agent.

The Output of First Stage Larvae by Cats Infested with Aelurostrongylus abstrusus

1968 ◽  
Vol 42 (3-4) ◽  
pp. 295-298 ◽  
Author(s):  
J. M. Hamilton ◽  
A. W. McCaw
Keyword(s):  
Life Cycle ◽  
Great Britain ◽  
Intermediate Host ◽  
World Wide ◽  
Wide Distribution ◽  
Clinical Disease ◽  
Complex Life Cycle ◽  
Patent Period ◽  
Aelurostrongylus Abstrusus

Aelurostrongylus abstrusus, the lungworm of the cat, has a world wide distribution and has been reported from countries as far apart as America, Great Britain and Palestine. It has a complex life cycle insofar as a molluscan intermediate host is essential and it is possible that auxiliary hosts also play an important part. In Britain, the incidence of active infestation of cats with the parasite has been recorded as 19·4% (Lewis, 1927) and 6·6% (Hamilton, 1966) but the latter author found that, generally, the clinical disease produced by the parasite was of a mild nature. It is known that the average patent period of the infestation in the cat is 8–13 weeks and it seems likely that, in that time, a considerable number of first stage larvae would be evacuated. Information on that point is not available and the object of the following experiment was to ascertain the number of larvae produced by cats during the course of a typical infestation.

scholarly journals Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qianshuo Liu ◽  
Xiaobai Liu ◽  
Defeng Zhao ◽  
Xuelei Ruan ◽  
Rui Su ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Vital Role ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Novel Target ◽  
And Function

AbstractThe blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

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