Spatial Localisation of Actin Filaments across Developmental Stages of the Malaria Parasite

We studied the response of the actin cytoskeleton in vetch root hairs after application of host-specific Nod factor. Within 3 to 15 min, the number of sub-apical fine bundles of actin filaments (FB-actin) increased in all developmental stages. Tip growth resumed only in hairs in which the FB-actin density and the length of the region with FB-actin exceeded a minimal value.

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Experiments upon the feeding of Aëdes aegypti through animal membranes with a view to applying this method to the chemotherapy of malaria

Parasitology ◽

10.1017/s0031182000013202 ◽

1946 ◽

Vol 37 (1-2) ◽

pp. 85-100 ◽

Cited By ~ 53

Author(s):

Ann Bishop ◽

Barbara M. Gilchrist

Keyword(s):

Aedes Aegypti ◽

Whole Blood ◽

Malaria Parasite ◽

Developmental Stages ◽

Tissue Cultures ◽

Infection Rates ◽

Infected Chicken ◽

Chicken Skin ◽

Chicken Blood

1. Membranes prepared from chicken skin provide a suitable medium through which Aëdes aegypti females may be induced to gorge.2. Under suitable conditions the proportion of female A. aegypti which will gorge through membranes, though more variable than when a living chick is offered, is great enough for experimental purposes.3. It is shown that the gorging reaction in A. aegypti is provoked by a heat gradient between the environment and the food-limiting membrane.4. The feeding reactions of A. aegypti towards whole blood, fractions of blood, and other sub-stances have been studied. It was found that (a) whole blood, and red corpuscles in saline when ingested through membranes go directly into the stomach which becomes fully distended; (b) haemoglobin in plasma or distilled water is ingested to a lesser degree than whole blood or red corpuscles in saline, and plasma alone is rarely ingested, but all these pass to the stomach; (c) sweet solutions containing glucose or honey are seldom imbibed through membranes and pass to the stomach or diverticula, but only the diverticula are fully distended.When offered as open drops (a) blood is seldom ingested, but if ingested passes to the stomach; (b) haemoglobin in plasma or water, or plasma alone, are very rarely ingested, but pass mainly to the stomach; (c) sweet solutions containing honey or glucose, or mixtures of blood and honey are readily ingested and pass mainly to the diverticula which become fully distended, though traces may be found in the stomach.5. Aëdes aegypti may be infected with Plasmodium gallinaceum by allowing them to gorge on drawn infected chicken blood through a membrane. Infection rates comparable to those obtained when the mosquitoes are fed directly on living chickens may be obtained by this method.6. If infected mosquitoes are allowed to gorge upon uninfected blood through membranes they eject viable sporozoites into the blood. When young chicks are injected intravenously with blood so infected, infections are produced which in period of incubation and intensity are comparable with those resulting from the bites of infected mosquitoes.7. The ejection of sporozoites through membranes in this manner provides a ready means of obtaining sporozoites free from glandular tissue.8. Sporozoites collected by this method will be suitable for in vitro experiments upon the action of drugs on sporozoites, and also as a source of material for studying in tissue cultures the developmental stages of the malaria parasite arising directly from the sporozoite.We wish to thank Prof. D. Keilin, F.R.S., and Dr P. Tate for helpful criticism and advice during the course of the work.

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Paleohaemoproteus burmacis gen. n., sp. n. (Haemospororida: Plasmodiidae) from an Early Cretaceous biting midge (Diptera: Ceratopogonidae)

Parasitology ◽

10.1017/s0031182005007298 ◽

2005 ◽

Vol 131 (1) ◽

pp. 79-84 ◽

Cited By ~ 21

Author(s):

G. POINAR ◽

S. R. TELFORD

Keyword(s):

Early Cretaceous ◽

Malaria Parasite ◽

Developmental Stages ◽

Abdominal Cavity ◽

Malarial Parasite ◽

Fossil Species ◽

Extinct Species ◽

Biting Midge ◽

Extant Species ◽

Wide Range

Paleohaemoproteus burmacis gen. n., sp. n. (Haemospororida: Plasmodiidae) is described from the abdominal cavity of a female biting midge (Diptera: Ceratopogonidae) preserved in 100 million year old amber from Myanmar (Burma). The description is based on the developmental stages of oocysts and sporozoites. The fossil species differs from extant species of Haemoproteus by its wide range of oocyst sizes, small sporozoites and occurrence in an extinct species of biting midge. Numerous sporozoites in the abdominal cavity suggest that the biting midge was an effective vector of this malarial parasite. Characters of the biting midge suggest that the host was a large, cold-blooded vertebrate. This is the earliest record of a malaria parasite and first indication that Early Cretaceous reptiles were infected with haemosporidial parasites.

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Calcium in the Backstage of Malaria Parasite Biology

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.708834 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lucas Silva de Oliveira ◽

Marcos Rodrigo Alborghetti ◽

Renata Garcia Carneiro ◽

Izabela Marques Dourado Bastos ◽

Rogerio Amino ◽

...

Keyword(s):

Life Cycle ◽

Protein Kinases ◽

Malaria Parasite ◽

Developmental Stages ◽

Receptor Gene ◽

Food Vacuole ◽

Parasite Development ◽

Cell Infection ◽

Parasite Life Cycle ◽

Downstream Signaling

The calcium ion (Ca2+) is a ubiquitous second messenger involved in key biological processes in prokaryotes and eukaryotes. In Plasmodium species, Ca2+ signaling plays a central role in the parasite life cycle. It has been associated with parasite development, fertilization, locomotion, and host cell infection. Despite the lack of a canonical inositol-1,4,5-triphosphate receptor gene in the Plasmodium genome, pharmacological evidence indicates that inositol-1,4,5-triphosphate triggers Ca2+ mobilization from the endoplasmic reticulum. Other structures such as acidocalcisomes, food vacuole and mitochondria are proposed to act as supplementary intracellular Ca2+ reservoirs. Several Ca2+-binding proteins (CaBPs) trigger downstream signaling. Other proteins with no EF-hand motifs, but apparently involved with CaBPs, are depicted as playing an important role in the erythrocyte invasion and egress. It is also proposed that a cross-talk among kinases, which are not members of the family of Ca2+-dependent protein kinases, such as protein kinases G, A and B, play additional roles mediated indirectly by Ca2+ regulation. This statement may be extended for proteins directly related to invasion or egress, such as SUB1, ERC, IMC1I, IMC1g, GAP45 and EBA175. In this review, we update our understanding of aspects of Ca2+-mediated signaling correlated to the developmental stages of the malaria parasite life cycle.

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New insights into antimalarial chemopreventive activity of antifolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01538-21 ◽

2021 ◽

Author(s):

Chatpong Pethrak ◽

Navaporn Posayapisit ◽

Jutharat Pengon ◽

Nattida Suwanakitti ◽

Atiporn Saeung ◽

...

Keyword(s):

Malaria Parasite ◽

Developmental Stages ◽

Cost Effective ◽

Asexual Blood Stage ◽

New Class ◽

Cost Effective Treatment ◽

Quadruple Mutant ◽

Stage Development ◽

Chemopreventive Activity ◽

Hepatic Development

Antifolates targeting dihydrofolate reductase (DHFR) are antimalarial compounds that have long been used for malaria treatment and chemoprevention (inhibition of infection from mosquitoes to humans). Despite their extensive applications, the thorough understanding of antifolate activity against hepatic malaria parasites, especially resistant parasites, have yet to be achieved. Using a transgenic P. berghei harboring quadruple mutant dhfr from P. falciparum (Pb::Pfdhfr -4M ) , we demonstrate that quadruple mutations on Pfdhfr confer complete chemoprevention resistance to pyrimethamine, the previous generation of antifolate, but not to a new class of antifolate designed to overcome the resistance such as P218. Detailed investigation to pin-point stage-specific chemoprevention further demonstrated that it is unnecessary for the drug to be present throughout hepatic development. The drug is most potent against the developmental stages from early hepatic trophozoite to late hepatic trophozoite, but is not effective at inhibiting sporozoite and early hepatic stage development from sporozoite to early trophozoite. Our data shows that P218 also inhibited the late hepatic stage development, from trophozoite to mature schizonts to a lesser extent. With a single dose of 15 mg/kg, P218 prevented infection from up to 25,000 pyrimethamine-resistant sporozoites, a number equal to thousands of infectious mosquito bites. Additionally, the hepatic stage of malaria parasite is much more susceptible to antifolates than the asexual blood stage. This study provides important insights into the activity of antifolates, as a chemopreventive therapeutic which could lead to a more efficient and cost effective treatment regime.

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Malaria Parasite Actin Filaments are Very Short

Journal of Molecular Biology ◽

10.1016/j.jmb.2005.03.056 ◽

2005 ◽

Vol 349 (1) ◽

pp. 113-125 ◽

Cited By ~ 109

Author(s):

Stephan Schmitz ◽

Munira Grainger ◽

Steven Howell ◽

Lesley J. Calder ◽

Martina Gaeb ◽

...

Keyword(s):

Actin Filaments ◽

Malaria Parasite

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New insights into antimalarial chemopreventive activity of antifolates

10.1101/2021.08.17.456746 ◽

2021 ◽

Author(s):

Chatpong Pethrak ◽

Navaporn Posayapisit ◽

Jutharat Pengon ◽

Nattida Suwanakitti ◽

Atiporn Saeung ◽

...

Keyword(s):

Malaria Parasite ◽

Developmental Stages ◽

Cost Effective ◽

Asexual Blood Stage ◽

New Class ◽

Cost Effective Treatment ◽

Quadruple Mutant ◽

Stage Development ◽

Chemopreventive Activity ◽

Hepatic Development

Antifolates targeting dihydrofolate reductase (DHFR) are antimalarial compounds that have long been used for malaria treatment and chemoprevention (inhibition of infection from mosquitoes to humans). Despite their extensive applications, the thorough understanding of antifolate activity against hepatic malaria parasites, especially resistant parasites, have yet to be achieved. Using a transgenic P. berghei harboring quadruple mutant dhfr from P. falciparum (Pb::Pfdhfr-4M), we demonstrate that quadruple mutations on Pfdhfr confer complete chemoprevention resistance to pyrimethamine, the previous generation of antifolate, but not a new class of antifolate designed to overcome the resistance such as P218. Detailed investigation to pin-point stage-specific chemoprevention further demonstrated that it is unnecessary for the drug to be present throughout hepatic development. The drug is most potent against the developmental stages from early hepatic trophozoite to late hepatic trophozoite, but is not effective at inhibiting sporozoite and early hepatic stage development from sporozoite to early trophozoite. Our data shows that P218 also inhibited the late hepatic stage development, from trophozoite to mature schizonts to a lesser extent. With a single dose of 15 mg/kg, P218 prevented infection from up to 25,000 pyrimentamine-resistant sporozoites, a number equal to thousands of infectious mosquito bites. Additionally, the hepatic stage of malaria parasite is much more susceptible to antifolates than the asexual blood stage. This study provides important insights into the activity of antifolates, as a chemopreventive therapeutic which could lead to a more efficient and cost effective treatment regime.

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Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1707506114 ◽

2017 ◽

Vol 114 (40) ◽

pp. 10636-10641 ◽

Cited By ~ 32

Author(s):

Sabrina Pospich ◽

Esa-Pekka Kumpula ◽

Julian von der Ecken ◽

Juha Vahokoski ◽

Inari Kursula ◽

...

Keyword(s):

High Resolution ◽

Host Cell ◽

Cell Invasion ◽

Atomic Structure ◽

Actin Filaments ◽

Malaria Parasite ◽

Structural Basis ◽

Host Cell Invasion ◽

Electron Cryomicroscopy ◽

Apicomplexan Parasites

During their life cycle, apicomplexan parasites, such as the malaria parasite Plasmodium falciparum, use actomyosin-driven gliding motility to move and invade host cells. For this process, actin filament length and stability are temporally and spatially controlled. In contrast to canonical actin, P. falciparum actin 1 (PfAct1) does not readily polymerize into long, stable filaments. The structural basis of filament instability, which plays a pivotal role in host cell invasion, and thus infectivity, is poorly understood, largely because high-resolution structures of PfAct1 filaments were missing. Here, we report the near-atomic structure of jasplakinolide (JAS)-stabilized PfAct1 filaments determined by electron cryomicroscopy. The general filament architecture is similar to that of mammalian F-actin. The high resolution of the structure allowed us to identify small but important differences at inter- and intrastrand contact sites, explaining the inherent instability of apicomplexan actin filaments. JAS binds at regular intervals inside the filament to three adjacent actin subunits, reinforcing filament stability by hydrophobic interactions. Our study reveals the high-resolution structure of a small molecule bound to F-actin, highlighting the potential of electron cryomicroscopy for structure-based drug design. Furthermore, our work serves as a strong foundation for understanding the structural design and evolution of actin filaments and their function in motility and host cell invasion of apicomplexan parasites.

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Effects of cytochalasin B on the formation of previllous ridges and the appearance of long microvillous-like processes in the organ culture system of chick embryonic intestine

Development ◽

10.1242/dev.85.1.47 ◽

1985 ◽

Vol 85 (1) ◽

pp. 47-64

Author(s):

Setsuko Noda

Keyword(s):

Epithelial Cells ◽

Organ Culture ◽

Actin Filaments ◽

Culture System ◽

Cytochalasin B ◽

Developmental Stages ◽

Cytochalasin D ◽

Short Exposure ◽

Cell Sheets ◽

Organ Culture System

Between 8 and 12 days of incubation the embryonic duodenum serially constructs with relative regularity the previllous ridges upon which the definitive villi later form. The effects of cytochalasin B (CB) on the formation of these previllous ridges of the duodena of developing chick embryos were studied, varying the concentrations and exposure time of CB in the organ culture system. The results were as follows:- (1) CB inhibited the formation of new previllous ridges from the epithelial cell sheets of 8- to 11-day-old embryonic duodena at a cultured time of 24 h. (2) CB treatment blocked or delayed cytokinesis of the epithelial cells and the production of many long microvillous-like processes (long processes) from the surface of the epithelial cells. (3) These long processes elicited by CB contained actin filaments and their appearance was influenced by the developmental stages of embryos and local parts of epithelial cells. (4) With 11-day embryonic duodena, induction of long processes by CB was observed at various concentrations (1 μg/ml–16 μg/ml) and even after short exposure of 15 min. (5) Cytochalasin D (CD) and colchicine were used and long processes were induced by CD but not by colchicine itself. The appearance of long processes depended on the experimental concentration of CB, CD and colchicine. In normal developments, such long processes appeared and disappeared within a confined area during the formation of previllous ridges (Noda, 1981). This study seemed to provide experimental support for the previous reported suggestion that the long processes might be one of the important factors in the formation of the previllous ridges of chick embryonic duodena.

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