scholarly journals Expanding the antimalarial toolkit: Targeting host–parasite interactions

2016 ◽  
Vol 213 (2) ◽  
pp. 143-153 ◽  
Author(s):  
Jean Langhorne ◽  
Patrick E. Duffy
Keyword(s):  
First Generation ◽  
Host Cells ◽  
Mammalian Host ◽  
Drug Resistant ◽  
Intracellular Growth ◽  
Partial Protection ◽  
Anopheles Mosquitoes ◽  
Host Parasite Interactions ◽  
New Research ◽  
Host Parasite

Recent successes in malaria control are threatened by drug-resistant Plasmodium parasites and insecticide-resistant Anopheles mosquitoes, and first generation vaccines offer only partial protection. New research approaches have highlighted host as well as parasite molecules or pathways that could be targeted for interventions. In this study, we discuss host–parasite interactions at the different stages of the Plasmodium life cycle within the mammalian host and the potential for therapeutics that prevent parasite migration, invasion, intracellular growth, or egress from host cells, as well as parasite-induced pathology.

scholarly journals Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development

2019 ◽  
Author(s):  
Arporn Wangwiwatsin ◽  
Anna V. Protasio ◽  
Shona Wilson ◽  
Christian Owusu ◽  
Nancy E. Holroyd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Schistosoma Mansoni ◽  
Chronic Infection ◽  
Egg Laying ◽  
Mammalian Host ◽  
Expression Data ◽  
Mammalian Development ◽  
Host Parasite Interactions ◽  
Parasitic Flatworm ◽  
Host Parasite

AbstractSchistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host–parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.Author SummaryThe life cycle of the parasitic flatworm Schistosoma mansoni is split between snail and mammalian (often human) hosts. An infection can last for more than 10 years, during which time the parasite physically interacts with its mammalian host as it moves through the bloodstream, travelling through the lungs and liver, to eventually establish a chronic infection in the blood vessels around the host gut. Throughout this complex journey, the parasite develops from a relatively simple larval form into a more complex, sexually reproducing adult. To understand the molecular basis of parasite interactions with the host during this complex journey we have produced genome-wide expression data from developing parasites. The parasites were collected from experimentally-infected mice over its developmental time-course from the poorly studied lung stage, to the fully mature egg-laying adult worm. The data highlight many genes involved in processes known to be associated with key stages of the infection. In addition, the gene expression data provide a unique view of interactions between the parasite and the immune system in the lung, including novel players in host-parasite interactions. A detailed understanding of these processes may provide new opportunities to design intervention strategies, particularly those focussed on the early stages of the infection that are not targeted by current chemotherapy.

scholarly journals Critical aspects of phytoalexins in potato

1987 ◽  
Vol 59 (3) ◽  
pp. 217-230
Author(s):  
Sture Brishammer
Keyword(s):  
Host Cells ◽  
Potato Tubers ◽  
Inhibitory Effects ◽  
Host Parasite Interactions ◽  
Different Types ◽  
Endogenous Elicitor ◽  
Artificial Inoculations ◽  
Host Parasite ◽  
Critical Aspects

Phytoalexins in potato are sesquiterpenoid substances produced in response to infections and are believed to help plants resist attack by pathogens. However, these compounds appear in response to compatible as well as incompatible interactions and only accumulate in the tubers. The amounts of phytoalexins produced depend on the physiological condition of the tubers. Young tubers don’t get easily infected with Phytophthora infestans even though they synthesize extremely small amounts of phytoalexins. Furthermore, confusion as to the identity of specific races and the propensity for a given race to produce different effects in the same type of host makes it extremely difficult to predict host-parasite interactions with any acceptable degree of accuracy. It is doubtful that the production of phytoalexins in response to artificial inoculations is representative of that occurring in natural infections. Markedly different types of pathogens induce synthesis of same substances in the host cells. It therefore seems most probable that all the phytoalexins are synthesized in response to stimulation by an endogenous elicitor. Little knowledge is available regarding the biosynthesis of these sesquiterpenes, and many previous determinations have presumably been erroneous. When potato tubers were inoculated with the late blight fungus, secondarily appearing bacteria were not retarded, despite the presence of phytoalexins. There is no generally accepted hypothesis describing the mechanism by which phytoalexins inhibit pathogens and no distinction has been made between the effects on necrotrophs and biotrophs. Adequate bioassays capable of measuring the effects of inhibition have yet to be developed, thus far, no convincing inhibitory effects have been reported. During purification of the phytoalexins there is a high risk for artifact forming, implying that specific compounds cannot be detected with certainty. Moreover, present analytical methods must be improved before we can determine how phytoalexins act in vivo. Probably, phytoalexins are synthesized at a stage in the infection too late to be able to restrict its expansion with the tissues of the host. Phytoalexins are restricted to the attacked parts of the tubers and there is no evidence indicating that these compounds pose any health risks when present in potatoes used for consumption.

scholarly journals Trichomonas vaginalis: current understanding of host–parasite interactions

2011 ◽  
Vol 51 ◽  
pp. 161-175 ◽  
Author(s):  
Christopher M. Ryan ◽  
Natalia de Miguel ◽  
Patricia J. Johnson
Keyword(s):  
Drug Targets ◽  
Trichomonas Vaginalis ◽  
Molecular Data ◽  
Host Cells ◽  
Current Status ◽  
Rational Approach ◽  
Sexually Transmitted ◽  
Host Parasite Interactions ◽  
Future Challenges ◽  
Host Parasite

Trichomonas vaginalis is a sexually transmitted obligate extracellular parasite that colonizes the human urogenital tract. Despite being of critical importance to the parasite's survival relatively little is known about the mechanisms employed by T. vaginalis to establish an infection and thrive within its host. Several studies have focused on the interaction of the parasite with host cells and extracellular matrix, identifying multiple suspected T. vaginalis adhesins. However, with the exception of its surface lipophosphoglycan, the evidence supporting a role in adhesion is indirect or controversial for many candidate molecules. The availability of the T. vaginalis genome sequence paved the way for genomic analyses to search for proteins possibly involved in host–parasite interactions. Several proteomic analyses have also provided insight into surface, soluble and secreted proteins that may be involved in Trichomonas pathogenesis. Although the accumulation of molecular data allows for a more rational approach towards identifying drug targets and vaccine candidates for this medically important parasite, a continued effort is required to advance our understanding of its biology. In the present chapter, we review the current status of research aimed at understanding T. vaginalis pathogenesis. Applied experimental approaches, an overview of significant conclusions drawn from this research and future challenges are discussed.

scholarly journals FLAgellum Member 8 modulates extravascular trypanosome distribution in the mammalian host

2021 ◽  
Author(s):  
Estefanía Calvo Alvarez ◽  
Aline Crouzols ◽  
Brice Rotureau
Keyword(s):  
Blood Circulation ◽  
Parasite Development ◽  
Mammalian Host ◽  
Host Parasite Interactions ◽  
Flagellar Protein ◽  
Host Parasite ◽  
Parasite Populations ◽  
Extravascular Compartment ◽  
Host Tissues

The African trypanosome flagellum is essential in multiple aspects of the parasite development. In the mammalian infective form of this protist, FLAgellar Member 8 (FLAM8) is a large protein distributed along the entire flagellum that is suspected to be involved in host-parasite interactions. Analyses of knockdown and knockout trypanosomes demonstrated that FLAM8 is not essential in vitro for survival, growth, motility and slender to stumpy differentiation. Functional investigations in experimental infections showed that FLAM8 -deprived trypanosomes are able to establish and maintain the infection in the blood circulation, and to differentiate into transmissible stumpy forms. However, bioluminescence imaging revealed that FLAM8 -null parasites exhibit an impaired dissemination in the extravascular compartment, especially in the skin, that is partially restored by the addition of a single rescue copy of FLAM8 . To our knowledge, FLAM8 is the first example of a flagellar protein that modulates T. brucei parasite distribution in the host tissues, contributing to the maintenance of extravascular parasite populations in mammalian anatomical niches.

A new technique for manipulating host–parasite interactions by low speed centrifugation

1978 ◽  
Vol 56 (5) ◽  
pp. 542-545 ◽  
Author(s):  
Margaret A. Waterman ◽  
James R. Aist ◽  
Herbert W. Israel
Keyword(s):  
Host Response ◽  
Host Cells ◽  
Plant Tissues ◽  
Powdery Mildew Fungus ◽  
Host Cytoplasm ◽  
Erysiphe Graminis Hordei ◽  
Host Parasite Interactions ◽  
Simultaneous Comparisons ◽  
A New Technique ◽  
Host Parasite

An apparatus and a method for centrifuging living, inoculated plant tissues were developed for studies of a cytoplasm-related host response of barley coleoptiles to penetration by the powdery mildew fungus Erysiphe graminis hordei. When the coleoptiles were attached to the apparatus with the long axes of the cells parallel to the centrifugal force, cytoplasm-rich and cytoplasm-poor zones were produced, permitting simultaneous comparisons of interactions in the presence or absence of host cytoplasm. The inner epidermis was inoculated and centrifuged for 12–14 h at 4750 × g. Desiccation was prevented by addition of liquids at the cut end of each coleoptile; the rest of the coleoptile was dry and suitable for inoculation with E. graminis conidia. Of the host cells, 50–80% had well-compacted cytoplasm, conidia developed penetration and infection structures, and the host response was restricted to cytoplasm-rich zones and was shown to be cytoplasm-dependent. Cytoplasmic streaming resumed within 10 min after centrifugation stopped, and 90–100% of the epidermal cells were actively streaming 3 h later. This centrifugation method could be adapted and applied to studies of the other host–parasite interactions.

scholarly journals Biochemical Characterization and Functional Studies of Acanthamoeba Mannose-Binding Protein

2005 ◽  
Vol 73 (9) ◽  
pp. 5775-5781 ◽  
Author(s):  
Marco Garate ◽  
Ibis Cubillos ◽  
Jeffrey Marchant ◽  
Noorjahan Panjwani
Keyword(s):  
Target Cell ◽  
Biochemical Characterization ◽  
Binding Protein ◽  
Host Cells ◽  
Neutral Sugar ◽  
Host Parasite Interactions ◽  
Mannose Binding Protein ◽  
Mannose Binding ◽  
Virulence Protein ◽  
Host Parasite

ABSTRACT Acanthamoebae produce a painful, sight-threatening corneal infection. The adhesion of parasites to the host cells is a critical first step in the pathogenesis of infection. Subsequent to adhesion, the parasites produce a potent cytopathic effect (CPE) leading to target cell death. Recent studies showing that acanthamoebae express a mannose-binding protein (MBP) and that free α-mannose (α-Man) specifically inhibits the adhesion of parasites to host cells suggest that the MBP plays a key role in the pathogenesis of Acanthamoeba infection by mediating host-parasite interactions. However, direct evidence showing that Acanthamoeba MBP is a virulence protein has been lacking. In this study, we demonstrate that the polyclonal immunoglobulin Y (IgY) antibodies prepared against affinity-purified Acanthamoeba MBP markedly inhibit the adhesion of parasites to host cells. The antibody also inhibited the Acanthamoeba-induced CPE on host cells. In contrast, preimmune IgY did not influence either the adhesion of the parasites to host cells or the amoeba-induced CPE. Using a variety of approaches, including affinity chromatography on an α-Man gel, electrophoresis under native and denaturing conditions, biotinylation of cell surface proteins, and immunostaining, it was conclusively established that Acanthamoeba MBP is located on the surface membranes of the parasites. Neutral-sugar analysis and lectin binding experiments using succinylated concanavalin A, a plant lectin with high affinity for mannose, revealed that Acanthamoeba MBP is itself a mannose-containing glycoprotein. N-Glycanase treatment to remove N-linked oligosaccharides shifted the subunit molecular mass of MBP from 130 kDa to 110 kDa. Hexosamine analysis revealed that Acanthamoeba MBP lacks detectable levels of GalNAc, suggesting the absence of O-linked oligosaccharides. In summary, we have characterized Acanthamoeba MBP and have shown that it is a major virulence protein responsible for host-parasite interactions and the parasite-induced target cell destruction.

THE IMPORTANCE OF COINCIDENCE IN THE FUNCTIONAL AND NUMERICAL RESPONSES OF TWO PARASITES OF THE EUROPEAN PINE SAWFLY, NEODIPRION SERTIFER

1969 ◽  
Vol 101 (7) ◽  
pp. 673-713 ◽  
Author(s):  
K. J. Griffiths
Keyword(s):  
Functional Response ◽  
First Generation ◽  
Initial Conditions ◽  
Host Density ◽  
Parasite Development ◽  
Neodiprion Sertifer ◽  
Pine Sawfly ◽  
Host Parasite Interactions ◽  
European Pine Sawfly ◽  
Host Parasite

AbstractThe possibility of imperfect coincidence between the appropriate stages of Neodiprion sertifer (Geoff.) and two of its important parasites was demonstrated. One of the parasites, the indigenous ichneumonid Exenterus canadensis Prov., which attacks late-stage larvae, has good spatial coincidence; but some members of each generation suffer from imperfect temporal coincidence, or asynchrony, caused by the interaction of temperature influence on parasite development rate and temperature variability between development sites in the litter. The second parasite, Pleolophus basizonus (Grav.), is an introduced, multivoltine ichneumonid cocoon parasite. It may be imperfectly synchronized in its first generation each year and may show imperfect spatial coincidence in all generations through its inability to attack host cocoons beneath approximately 1 in. or more of litter.The intricate relations between parasite and host density, time, attack, and coincidence were investigated using the basic functional response submodel developed by Holling, a submodel that describes changes in oviposition behaviour with time, and a submodel that predicts the number of hosts attacked, given the number of eggs laid and data on the distribution of eggs among hosts. In the two species studied, the effect of asynchrony in one generation cannot be considered without considering the influence of superparasitism. At low host densities, superparasitism largely buffers the effects of decreased synchrony. This buffering effect decreases as host density increases until when each parasite is attacking all the hosts it can, it is almost eliminated. Imperfect spatial coincidence in one generation merely lowers the usable host density. Thus its effect can be seen in the functional response of the parasite to host density. When host–parasite interactions over 25 to 35 host generations were simulated, using initial conditions resembling those ensuing when small numbers of both host and parasite invade a previously unattacked stand, populations became stable after passing through one or more oscillations. Decreasing temporal or spatial coincidence increased host and parasite densities at the peaks of oscillations and increased the ultimate steady density of host and parasite, until coincidence was reduced to nearly half. At this level, the host escaped the regulating ability of both species of parasites.

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