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 Recent Advances in Surface Nanoengineering for Biofilm Prevention and Control. Part I: Molecular Basis of Biofilm Recalcitrance. Passive Anti-Biofouling Nanocoatings

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1230 ◽  
Author(s):  
Paul Cătălin Balaure ◽  
Alexandru Mihai Grumezescu
Keyword(s):  
Life Cycle ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Current Knowledge ◽  
Emergent Properties ◽  
Bacterial Cells ◽  
Life Cycle Stages ◽  
Fouling Release ◽  
Biofilm Development ◽  
And Control

Medical device-associated infections are becoming a leading cause of morbidity and mortality worldwide, prompting researchers to find new, more effective ways to control the bacterial colonisation of surfaces and biofilm development. Bacteria in biofilms exhibit a set of “emergent properties”, meaning those properties that are not predictable from the study of free-living bacterial cells. The social coordinated behaviour in the biofilm lifestyle involves intricate signaling pathways and molecular mechanisms underlying the gain in resistance and tolerance (recalcitrance) towards antimicrobial agents as compared to free-floating bacteria. Nanotechnology provides powerful tools to disrupt the processes responsible for recalcitrance development in all stages of the biofilm life cycle. The present paper is a state-of-the-art review of the surface nanoengineering strategies currently used to design antibiofilm coatings. The review is structurally organised in two parts according to the targeted biofilm life cycle stages and molecular mechanisms intervening in recalcitrance development. Therefore, in the present first part, we begin with a presentation of the current knowledge of the molecular mechanisms responsible for increased recalcitrance that have to be disrupted. Further, we deal with passive surface nanoengineering strategies that aim to prevent bacterial cells from settling onto a biotic or abiotic surface. Both “fouling-resistant” and “fouling release” strategies are addressed as well as their synergic combination in a single unique nanoplatform.

scholarly journals Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites

mBio ◽  
2021 ◽  
Author(s):  
Emily S. Mathews ◽  
Andrew J. Jezewski ◽  
Audrey R. Odom John
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria ◽  
Complex Life Cycle ◽  
Large Temperature ◽  
Protein Prenylation ◽  
Content Type

During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum , and the canonical heat shock protein 40 protein (HSP40; PF3D7_1437900) is posttranslationally modified with a 15-carbon farnesyl isoprenyl group.

scholarly journals From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium

2020 ◽  
Vol 10 ◽  
Author(s):  
Thomas Hollin ◽  
Karine G. Le Roch
Keyword(s):  
Life Cycle ◽  
Malaria Parasite ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Tight Control ◽  
Control Of Gene Expression ◽  
Human Malaria Parasite ◽  
Stage Conversion ◽  
The Past

Over the past decade, we have witnessed significant progresses in understanding gene regulation in Apicomplexa including the human malaria parasite, Plasmodium falciparum. This parasite possesses the ability to convert in multiple stages in various hosts, cell types, and environments. Recent findings indicate that P. falciparum is talented at using efficient and complementary molecular mechanisms to ensure a tight control of gene expression at each stage of its life cycle. Here, we review the current understanding on the contribution of the epigenome, atypical transcription factors, and chromatin organization to regulate stage conversion in P. falciparum. The adjustment of these regulatory mechanisms occurring during the progression of the life cycle will be extensively discussed.

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 Autophagy in HCV Infection: Keeping Fat and Inflammation at Bay

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Tiziana Vescovo ◽  
Giulia Refolo ◽  
Alessandra Romagnoli ◽  
Fabiola Ciccosanti ◽  
Marco Corazzari ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Life Cycle ◽  
Liver Disease ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Viral Persistence ◽  
Hcv Infection ◽  
Lipid Homeostasis ◽  
Specific Host

Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease. Viral persistence and pathogenesis rely mainly on the ability of HCV to deregulate specific host processes, including lipid metabolism and innate immunity. Recently, autophagy has emerged as a cellular pathway, playing a role in several aspects of HCV infection. This review summarizes current knowledge on the molecular mechanisms that link the HCV life cycle with autophagy machinery. In particular, we discuss the role of HCV/autophagy interaction in dysregulating inflammation and lipid homeostasis and its potential for translational applications in the treatment of HCV-infected patients.

scholarly journals Past and future perspectives on mathematical models of tick-borne pathogens

Parasitology ◽  
2015 ◽  
Vol 143 (7) ◽  
pp. 850-859 ◽  
Author(s):  
R. A. NORMAN ◽  
A. J. WORTON ◽  
L. GILBERT
Keyword(s):  
Life Cycle ◽  
Mathematical Models ◽  
Environmental Conditions ◽  
Current Knowledge ◽  
Habitat Type ◽  
Spatial Models ◽  
Host Population ◽  
Complex Life Cycle ◽  
System Maps ◽  
Blood Meals

SUMMARYTicks are vectors of pathogens which are important both with respect to human health and economically. They have a complex life cycle requiring several blood meals throughout their life. These blood meals take place on different individual hosts and potentially on different host species. Their life cycle is also dependent on environmental conditions such as the temperature and habitat type. Mathematical models have been used for the more than 30 years to help us understand how tick dynamics are dependent on these environmental factors and host availability. In this paper, we review models of tick dynamics and summarize the main results. This summary is split into two parts, one which looks at tick dynamics and one which looks at tick-borne pathogens. In general, the models of tick dynamics are used to determine when the peak in tick densities is likely to occur in the year and how that changes with environmental conditions. The models of tick-borne pathogens focus more on the conditions under which the pathogen can persist and how host population densities might be manipulated to control these pathogens. In the final section of the paper, we identify gaps in the current knowledge and future modelling approaches. These include spatial models linked to environmental information and Geographic Information System maps, and development of new modelling techniques which model tick densities per host more explicitly.

scholarly journals Predicting gene expression in the human malaria parasite Plasmodium falciparum

2018 ◽  
Author(s):  
David F. Read ◽  
Yang Y. Lu ◽  
Kate Cook ◽  
Karine Le Roch ◽  
William Stafford Noble
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Histone Modifications ◽  
Malaria Parasite ◽  
Nucleosome Occupancy ◽  
Gc Content ◽  
Complex Life Cycle ◽  
Data Sets ◽  
3D Genome ◽  
Parasite Plasmodium Falciparum

AbstractEmpirical evidence suggests that the malaria parasite Plasmodium falciparum employs a broad range of mechanisms to regulate gene transcription throughout the organism’s complex life cycle. To better understand this regulatory machinery, we assembled a rich collection of genomic and epigenomic data sets, including information about transcription factor (TF) binding motifs, patterns of covalent histone modifications, nucleosome occupancy, GC content, and global 3D genome architecture. We used these data to train machine learning models to discriminate between high-expression and low-expression genes, focusing on three distinct stages of the red blood cell phase of the Plasmodium life cycle. Our results highlight the importance of histone modifications and 3D chromatin architecture and suggest a relatively small role for TF binding in Plasmodium transcriptional regulation.

scholarly journals Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria parasites

2021 ◽  
Author(s):  
Philip M Frasse ◽  
Justin J Miller ◽  
Ebrahim Soleimani ◽  
Jian-She Zhu ◽  
David L Jakeman ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Three Dimensional ◽  
Complex Life Cycle ◽  
Parasite Development ◽  
Gpi Anchor ◽  
Multi Stage ◽  
Transgenic Parasites ◽  
Parasite Egress ◽  
Dimensional Crystal

The malaria parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of GPI anchor biosynthesis, the putative phosphomannomutase (EC 5.4.2.8) of the parasites, HAD5 (PF3D7_1017400). We confirm the phosphomannomutase and phosphoglucomutase activity of purified recombinant HAD5. By regulating expression of HAD5 in transgenic parasites, we demonstrate that HAD5 is required for malaria parasite egress and erythrocyte reinvasion. Finally, we determine the three-dimensional crystal structure of HAD5 and identify a substrate analog that specifically inhibits HAD5, compared to orthologous human phosphomannomutases. These findings demonstrate that the GPI anchor biosynthesis pathway is exceptionally sensitive to inhibition, and that HAD5 has potential as a multi-stage antimalarial target.

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.

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