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1.
Ann Agric Environ Med ; 26(4): 523-531, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31885223

RESUMO

INTRODUCTION: Over 300 species of parasites can possibly be passed on humans. Most of the parasitic infections are defined based on their pathogenicity; however, some positive effects of a parasite existence within the human body have recently been suggested. Beneficial outcomes of parasite infections might result from the production and release of metabolites, modification of host immune response or products uptake of the host. OBJECTIVE: The aim of the study was a comprehensive analysis of a wide range of effects of parasites on the human body, including an overview of the toxic and positive effects. STATE OF KNOWLEDGE: In the light of the latest research presenting the unconventional use of parasites in medicine, the widely understood of their impact on the human body can also be considered in a positive context. Clinical cases from diseases caused by the toxic effects of parasites, as described in recent years, indicate that the problem of parasitic infections still persists. Despite a great deal of knowledge about the toxic effects of parasites on the human organism and, above all, despite the improvement in sanitary conditions, there is a resurgence of parasitic infections, as evidenced, e.g. by the examples presented in this review. CONCLUSIONS: The examples of positive effects of parasites presented so far give hope for the future in terms of fighting many diseases for which pharmacological treatment has not yet brought a positive effect. A better understanding of those processes might lead to the development of new methods of unconventional medical treatment.


Assuntos
Parasitos/química , Doenças Parasitárias/parasitologia , Animais , Humanos , Medicina , Parasitos/metabolismo , Doenças Parasitárias/imunologia
2.
Cell Host Microbe ; 26(4): 453-462, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600499

RESUMO

Calcium is an abundant intracellular ion, and calcium homeostasis plays crucial roles in several cellular processes. The calcineurin signaling cascade is one of the major pathways governed by intracellular calcium. Calcineurin, a conserved protein from yeast to humans, is a calcium-calmodulin-dependent serine-threonine-specific phosphatase that orchestrates cellular stress responses. In eukaryotic microbial pathogens, calcineurin controls essential virulence pathways, such as the ability to grow at host temperature, morphogenesis to enable invasive hyphal growth, drug tolerance and resistance, cell wall integrity, and sexual development. Therefore, the calcineurin cascade is an attractive target in drug development against eukaryotic pathogens. In the present review, we summarize and discuss the current knowledge on the roles of calcineurin in eukaryotic microbial pathogens, focusing on fungi and parasitic protists.


Assuntos
Calcineurina/metabolismo , Cálcio/metabolismo , Calmodulina/metabolismo , Fungos/patogenicidade , Parasitos/patogenicidade , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fungos/crescimento & desenvolvimento , Fungos/metabolismo , Humanos , Parasitos/crescimento & desenvolvimento , Parasitos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Virulência
3.
Molecules ; 24(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623105

RESUMO

Human parasitic protozoa cause a large number of diseases worldwide and, for some of these diseases, there are no effective treatments to date, and drug resistance has been observed. For these reasons, the discovery of new etiological treatments is necessary. In this sense, parasitic metabolic pathways that are absent in vertebrate hosts would be interesting research candidates for the identification of new drug targets. Most likely due to the protozoa variability, uncertain phylogenetic origin, endosymbiotic events, and evolutionary pressure for adaptation to adverse environments, a surprising variety of prenylquinones can be found within these organisms. These compounds are involved in essential metabolic reactions in organisms, for example, prevention of lipoperoxidation, participation in the mitochondrial respiratory chain or as enzymatic cofactors. This review will describe several prenylquinones that have been previously characterized in human pathogenic protozoa. Among all existing prenylquinones, this review is focused on ubiquinone, menaquinone, tocopherols, chlorobiumquinone, and thermoplasmaquinone. This review will also discuss the biosynthesis of prenylquinones, starting from the isoprenic side chains to the aromatic head group precursors. The isoprenic side chain biosynthesis maybe come from mevalonate or non-mevalonate pathways as well as leucine dependent pathways for isoprenoid biosynthesis. Finally, the isoprenic chains elongation and prenylquinone aromatic precursors origins from amino acid degradation or the shikimate pathway is reviewed. The phylogenetic distribution and what is known about the biological functions of these compounds among species will be described, as will the therapeutic strategies associated with prenylquinone metabolism in protozoan parasites.


Assuntos
Antineoplásicos/farmacologia , Antiprotozoários/farmacologia , Parasitos/efeitos dos fármacos , Quinonas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antiprotozoários/química , Antiprotozoários/metabolismo , Vias Biossintéticas , Humanos , Estrutura Molecular , Parasitos/metabolismo , Quinonas/química , Quinonas/metabolismo , Simbiose/efeitos dos fármacos
4.
Nat Commun ; 10(1): 4041, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492901

RESUMO

Members of the Apicomplexa phylum, including Plasmodium and Toxoplasma, have two types of secretory organelles (micronemes and rhoptries) whose sequential release is essential for invasion and the intracellular lifestyle of these eukaryotes. During invasion, rhoptries inject an array of invasion and virulence factors into the cytoplasm of the host cell, but the molecular mechanism mediating rhoptry exocytosis is unknown. Here we identify a set of parasite specific proteins, termed rhoptry apical surface proteins (RASP) that cap the extremity of the rhoptry. Depletion of RASP2 results in loss of rhoptry secretion and completely blocks parasite invasion and therefore parasite proliferation in both Toxoplasma and Plasmodium. Recombinant RASP2 binds charged lipids and likely contributes to assembling the machinery that docks/primes the rhoptry to the plasma membrane prior to fusion. This study provides important mechanistic insight into a parasite specific exocytic pathway, essential for the establishment of infection.


Assuntos
Proteínas de Transporte/metabolismo , Organelas/metabolismo , Fosfolipídeos/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Animais , Proteínas de Transporte/genética , Linhagem Celular , Exocitose , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/parasitologia , Interações Hospedeiro-Parasita , Humanos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Parasitos/metabolismo , Parasitos/ultraestrutura , Fosfolipídeos/química , Proteínas de Protozoários/genética
5.
PLoS Biol ; 17(8): e3000364, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31430281

RESUMO

Many eukaryotic microbes have complex life cycles that include both sexual and asexual phases with strict species specificity. Whereas the asexual cycle of the protistan parasite Toxoplasma gondii can occur in any warm-blooded mammal, the sexual cycle is restricted to the feline intestine. The molecular determinants that identify cats as the definitive host for T. gondii are unknown. Here, we defined the mechanism of species specificity for T. gondii sexual development and break the species barrier to allow the sexual cycle to occur in mice. We determined that T. gondii sexual development occurs when cultured feline intestinal epithelial cells are supplemented with linoleic acid. Felines are the only mammals that lack delta-6-desaturase activity in their intestines, which is required for linoleic acid metabolism, resulting in systemic excess of linoleic acid. We found that inhibition of murine delta-6-desaturase and supplementation of their diet with linoleic acid allowed T. gondii sexual development in mice. This mechanism of species specificity is the first defined for a parasite sexual cycle. This work highlights how host diet and metabolism shape coevolution with microbes. The key to unlocking the species boundaries for other eukaryotic microbes may also rely on the lipid composition of their environments as we see increasing evidence for the importance of host lipid metabolism during parasitic lifecycles. Pregnant women are advised against handling cat litter, as maternal infection with T. gondii can be transmitted to the fetus with potentially lethal outcomes. Knowing the molecular components that create a conducive environment for T. gondii sexual reproduction will allow for development of therapeutics that prevent shedding of T. gondii parasites. Finally, given the current reliance on companion animals to study T. gondii sexual development, this work will allow the T. gondii field to use of alternative models in future studies.


Assuntos
Linoleoil-CoA Desaturase/metabolismo , Toxoplasma/enzimologia , Animais , Gatos , Especificidade de Hospedeiro , Interações Hospedeiro-Parasita , Intestinos/parasitologia , Estágios do Ciclo de Vida/fisiologia , Ácido Linoleico/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Parasitos/metabolismo , Desenvolvimento Sexual/fisiologia , Especificidade da Espécie , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/patogenicidade
6.
Methods Mol Biol ; 1934: 145-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256378

RESUMO

Glycosylphosphatidylinositol (GPI) is a complex glycolipid structure that acts as a membrane anchor for many cell-surface proteins of eukaryotes. GPI-anchored proteins are particularly abundant in protozoa and represent the major carbohydrate modification of many cell-surface parasite proteins. A minimal GPI-anchor precursor consists of core glycan (ethanolamine-PO4-Manα1-2Manα1-6Manα1-4GlcNH2) linked to the 6-position of the D-myo-inositol ring of phosphatidylinositol. Although the GPI core glycan is conserved in all organisms, many differences in additional modifications to GPI structures and biosynthetic pathways have been reported. The preassembled GPI-anchor precursor is post-translationally transferred to a variety of membrane proteins in the lumen of the endoplasmic reticulum in a transamidase-like reaction during which a C-terminal GPI attachment signal is released. Increasing evidence shows that a significant proportion of the synthesized GPIs are not used for protein anchoring, particularly in protozoa in which a large amount of free GPIs are being displayed at the cell surface. The characteristics of GPI biosynthesis are currently being explored for the development of parasite-specific inhibitors. Especially this pathway, at least for Trypanosoma brucei, has been validated as a drug target. Furthermore, thanks to an increase of new innovative strategies to produce pure synthetic carbohydrates, a novel era in the use of GPIs in diagnostic, anti-GPI antibody production, as well as parasitic protozoa GPI-based vaccine approach is developing fast.


Assuntos
Glicosilfosfatidilinositóis/química , Parasitos/química , Animais , Glicolipídeos/química , Glicosilfosfatidilinositóis/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Redes e Vias Metabólicas , Parasitos/metabolismo , Fosforilação , Plasmodium falciparum/química , Polissacarídeos , Coloração e Rotulagem , Relação Estrutura-Atividade
7.
Curr Protein Pept Sci ; 20(9): 873-884, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31272352

RESUMO

ATP-diphosphohydrolases (EC 3.6.1.5), also known as ATPDases, NTPases, NTPDases, EATPases or apyrases, are enzymes that hydrolyze a variety of nucleoside tri- and diphosphates to their respective nucleosides, being their activities dependent on the presence of divalent cations, such as calcium and magnesium. Recently, ATP-diphosphohydrolases were identified on the surface of several parasites, such as Trypanosoma sp, Leishmania sp and Schistosoma sp. In parasites, the activity of ATPdiphosphohydrolases has been associated with the purine recuperation and/or as a protective mechanism against the host organism under conditions that involve ATP or ADP, such as immune responses and platelet activation. These proteins have been suggested as possible targets for the development of new antiparasitic drugs. In this review, we will comprehensively address the main aspects of the location and function of ATP-diphosphohydrolase in parasites. Also, we performed a detailed research in scientific database of recent developments in new natural and synthetic inhibitors of the ATPdiphosphohydrolases in parasites.


Assuntos
Trifosfato de Adenosina/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Parasitos/metabolismo , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Apirase/antagonistas & inibidores , Descoberta de Drogas , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Parasitos/efeitos dos fármacos
8.
Acta Trop ; 196: 30-36, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31071298

RESUMO

Parasites use excretory-secretory pathways to communicate with the host. Characterization of exosomes within the excretory-secretory products reveal by which parasites manipulate their hosts. Parasite derived exosomes provide a mechanistic framework for protein and miRNAs transfer. Transcriptomics and proteomics of parasite exosomes identified a large number of miRNAs and proteins being utilized by parasites in their survival, reproduction and development. Characterization of proteins and miRNAs in parasite secreted exosomes provide important information on host-parasite communication and forms the basis for future studies. In this review, we summarize recent advances in isolation and molecular characterization (protein and miRNAs) of parasite derived exosomes.


Assuntos
Exossomos/metabolismo , Parasitos/metabolismo , Animais , MicroRNAs , Proteínas/metabolismo , Proteômica , Transcriptoma
9.
PLoS Biol ; 17(5): e3000264, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31075098

RESUMO

Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites is poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase beta (ACß) and its downstream effector, cAMP-dependent protein kinase (PKA). We show that both production of cAMP and activity of PKA are critical for erythrocyte invasion, whilst key developmental steps that precede invasion still take place in the absence of cAMP-dependent signalling. We also show that another parasite protein with putative cyclic nucleotide binding sites, Plasmodium falciparum EPAC (PfEpac), does not play an essential role in blood stages. We identify and quantify numerous sites, phosphorylation of which is dependent on cAMP signalling, and we provide mechanistic insight as to how cAMP-dependent phosphorylation of the cytoplasmic domain of the essential invasion adhesin apical membrane antigen 1 (AMA1) regulates erythrocyte invasion.


Assuntos
AMP Cíclico/metabolismo , Interações Hospedeiro-Parasita , Malária Falciparum/metabolismo , Malária Falciparum/parasitologia , Parasitos/metabolismo , Transdução de Sinais , Adenilil Ciclases/metabolismo , Animais , Cálcio/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Parasitos/enzimologia , Parasitos/crescimento & desenvolvimento , Parasitos/ultraestrutura , Fosfoproteínas/metabolismo , Fosforilação , Fosfosserina/metabolismo , Plasmodium falciparum/enzimologia , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/patogenicidade , Plasmodium falciparum/ultraestrutura , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo
10.
Curr Top Microbiol Immunol ; 420: 155-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30105424

RESUMO

Parasites exist within most ecological niches, often transitioning through biologically and chemically complex host environments over the course of their parasitic life cycles. While the development of technologies for genetic engineering has revolutionised the field of functional genomics, parasites have historically been less amenable to such modification. In light of this, parasitologists have often been at the forefront of adopting new small-molecule technologies, repurposing drugs into biological tools and probes. Over the last decade, activity-based protein profiling (ABPP) has evolved into a powerful and versatile chemical proteomic platform for characterising the function of enzymes. Central to ABPP is the use of activity-based probes (ABPs), which covalently modify the active sites of enzyme classes ranging from serine hydrolases to glycosidases. The application of ABPP to cellular systems has contributed vastly to our knowledge on the fundamental biology of a diverse range of organisms and has facilitated the identification of potential drug targets in many pathogens. In this chapter, we provide a comprehensive review on the different forms of ABPP that have been successfully applied to parasite systems, and highlight key biological insights that have been enabled through their application.


Assuntos
Parasitos/metabolismo , Proteoma/análise , Proteoma/metabolismo , Proteômica/métodos , Infecções por Protozoários/metabolismo , Infecções por Protozoários/parasitologia , Animais , Domínio Catalítico , Humanos , Parasitos/enzimologia , Proteoma/química , Infecções por Protozoários/enzimologia
11.
Parasitol Res ; 118(2): 653-655, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30460538

RESUMO

Gnathiid isopods are common external parasites/micropredators that feed on the blood of marine fishes. During the course of processing samples of gnathiid isopods collected from light traps in the central Philippines, we observed a gnathiid attached to and apparently feeding from the abdomen of another gnathiid. Because the abdomens of both gnathiids were enlarged, it was unclear whether one actually fed on the blood meal of the other. Introduction of unfed gnathiids with fed gnathiids revealed that one gnathiid could and did feed on the blood meal of another. This is the first observation of apparent conspecific kleptoparasitism reported for gnathiid isopods.


Assuntos
Isópodes/parasitologia , Parasitos/metabolismo , Animais , Doenças dos Peixes/parasitologia , Peixes/parasitologia , Filipinas
12.
Parasitol Res ; 118(1): 363-367, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30465072

RESUMO

Parasites are widespread in natural environments, and their impacts on the fitness of their host and, at a broader scale, on ecosystem functioning are well recognized. Over the last two decades, there has been an increasing interest in the effects of parasites in conjunction with other stressors, especially pollutants, on the health of organisms. For instance, parasites can interfere with the bioaccumulation process of contaminants in their host leading to parasitized organisms exhibiting lower pollutants burdens than unparasitized individuals for example. However, the mechanisms underlying these patterns are not well understood. This study examined how the bopyrid parasite Gyge branchialis could lower the cadmium (Cd) uptake of its mud shrimp host Upogebia cf. pusilla. When exposed to water-borne Cd, parasites were able to bioaccumulate this trace metal. However, the uptake of Cd by the parasite was low and cannot entirely explain the deficit of Cd contamination of the host. The weight of gills of parasitized organisms was significantly reduced compared with unparasitized organisms. We suggest that by reducing the surface for metal uptake, parasites could lower the contaminant burden of their host.


Assuntos
Cádmio/metabolismo , /parasitologia , Isópodes/metabolismo , Parasitos/metabolismo , Animais , Cádmio/análise , Brânquias/crescimento & desenvolvimento , Brânquias/parasitologia , Oligoelementos/análise , Oligoelementos/metabolismo
13.
J Helminthol ; 93(1): 1-7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29486814

RESUMO

Parasites are often overlooked in the construction of food webs, despite their ubiquitous presence in almost every type of ecosystem. Researchers who do recognize their importance often struggle to include parasites using classical food-web theory, mainly due to the parasites' multiple hosts and life stages. A novel approach using compound-specific stable-isotope analysis promises to provide considerable insight into the energetic exchanges of parasite and host, which may solve some of the issues inherent in incorporating parasites using a classical approach. Understanding the role of parasites within food webs, and tracing the associated biomass transfers, are crucial to constructing new models that will expand our knowledge of food webs. This mini-review focuses on stable-isotope studies published in the past decade, and introduces compound-specific stable-isotope analysis as a powerful, but underutilized, newly developed tool that may answer many unresolved questions regarding the role of parasites in food webs.


Assuntos
Cadeia Alimentar , Isótopos/análise , Parasitos/fisiologia , Parasitologia/métodos , Animais , Biomassa , Ecossistema , Metabolismo Energético , Interações Hospedeiro-Parasita , Isótopos/metabolismo , Modelos Biológicos , Parasitos/metabolismo
14.
Exp Suppl ; 109: 421-458, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30535608

RESUMO

A complex network that embraces parasite-host intrinsic factors and the microenvironment regulated the interaction between a parasite and its host. Nutritional pressures exerted by both elements of this duet thus dictate this host-parasite niche. To survive and proliferate inside a host and a harsh nutritional environment, the parasites modulate different nutrient sensing pathways to subvert host metabolic pathways. Such mechanism is able to change the flux of distinct nutrients/metabolites diverting them to be used by the parasites. Apart from this nutritional strategy, the scavenging of nutrients, particularly host fatty acids, constitutes a critical mechanism to fulfil parasite nutritional requirements, ultimately defining the host metabolic landscape. The host metabolic alterations that result from host-parasite metabolic coupling can certainly be considered important targets to improve diagnosis and also for the development of future therapies. Metabolism is in fact considered a key element within this complex interaction, its modulation being crucial to dictate the final infection outcome.


Assuntos
Interações Hospedeiro-Patógeno , Redes e Vias Metabólicas , Parasitos/metabolismo , Animais , Fenômenos Fisiológicos da Nutrição
15.
Int J Mol Sci ; 19(12)2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30572624

RESUMO

Microsporidia are fungi-like parasites that have the smallest known eukaryotic genome, and for that reason they are used as a model to study the phenomenon of genome decay in parasitic forms of life. Similar to other intracellular parasites that reproduce asexually in an environment with alleviated natural selection, Microsporidia experience continuous genome decay that is driven by Muller's ratchet-an evolutionary process of irreversible accumulation of deleterious mutations that lead to gene loss and the miniaturization of cellular components. Particularly, Microsporidia have remarkably small ribosomes in which the rRNA is reduced to the minimal enzymatic core. In this study, we analyzed microsporidian ribosomes to study an apparent impact of Muller's ratchet on structure of RNA and protein molecules in parasitic forms of life. Through mass spectrometry of microsporidian proteome and analysis of microsporidian genomes, we found that massive rRNA reduction in microsporidian ribosomes appears to annihilate the binding sites for ribosomal proteins eL8, eL27, and eS31, suggesting that these proteins are no longer bound to the ribosome in microsporidian species. We then provided an evidence that protein eS31 is retained in Microsporidia due to its non-ribosomal function in ubiquitin biogenesis. Our study illustrates that, while Microsporidia carry the same set of ribosomal proteins as non-parasitic eukaryotes, some ribosomal proteins are no longer participating in protein synthesis in Microsporidia and they are preserved from genome decay by having extra-ribosomal functions. More generally, our study shows that many components of parasitic cells, which are identified by automated annotation of pathogenic genomes, may lack part of their biological functions due to continuous genome decay.


Assuntos
Espaço Intracelular/parasitologia , Microsporídios/metabolismo , Parasitos/metabolismo , Ribossomos/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Evolução Biológica , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , RNA Ribossômico/metabolismo , Proteínas Ribossômicas/metabolismo
16.
Biomed Res Int ; 2018: 1641839, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30406129

RESUMO

Nucleogenesis is the cellular event responsible for the formation of the new nucleoli at the end of mitosis. This process depends on the synthesis and processing of ribosomal RNA (rRNA) and, in some eukaryotes, the transfer of nucleolar material contained in prenucleolar bodies (PNBs) to active transcription sites. The lack of a comprehensive description of the nucleolus throughout the cell cycle of the human pathogen Leishmania major prompted us to analyze the distribution of nucleolar protein 56 (Nop56) during interphase and mitosis in the promastigote stage of the parasite. By in silico analysis we show that the orthologue of Nop56 in L. major (LmNop56) contains the three characteristic Nop56 domains and that its predicted three-dimensional structure is also conserved. Fluorescence microscopy observations indicate that the nucleolar localization of LmNop56 is similar, but not identical, to that of the nucleolar protein Elp3b. Notably, unlike other nucleolar proteins, LmNop56 remains associated with the nucleolus in nonproliferative cells. Moreover, epifluorescent images indicate the preservation of the nucleolar structure throughout the closed nuclear division. Experiments performed with the related parasite Trypanosoma brucei show that nucleolar division is carried out by an analogous mechanism.


Assuntos
Divisão Celular , Nucléolo Celular/metabolismo , Leishmania major/crescimento & desenvolvimento , Leishmania major/metabolismo , Estágios do Ciclo de Vida , Parasitos/crescimento & desenvolvimento , Parasitos/metabolismo , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Animais , Sequência Conservada , Evolução Molecular , Humanos , Mitose , Proteínas de Protozoários/química , Trypanosoma brucei brucei/metabolismo
17.
Gen Comp Endocrinol ; 269: 166-170, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30244054

RESUMO

Social regulation of reproductive hormones is a means by which conspecific males and females orchestrate successful reproductive efforts. We investigate whether social cues modify activity within the hypothalamic-pituitary-gonadal (HPG) axis and the specificity of this response in a social parasite that is known to eavesdrop on the communication signals of other species: the brown-headed cowbird (Molothrus ater). Brown-headed cowbirds are obligate brood parasites that do not build nests or care for their own young. Instead, obligate brood parasites leave their eggs in the nest of a host species and therefore must coordinate their breeding attempts with conspecifics as well as potential heterospecific hosts. Here, we explore whether the vocal signals of potential host species can also be used as a social cue that modifies the HPG axis of female brown-headed cowbirds. Results reveal that both conspecific and heterospecific song-exposed females exhibit significantly greater circulating estradiol concentrations as compared to silence-exposed females. While conspecific song induces the greatest elevation in circulating estradiol, there is no significant difference in circulating estradiol levels in females exposed to either conspecific or heterospecific songs. This pattern suggests both song types are effective at evoking a reproductive physiological response. On the other hand, circulating progesterone concentrations did not differ among the song- and silence-exposed groups nor did the size of the female's ovarian follicles. These results indicate that heterospecific vocal communication signals can effectively be used as a social cue that simultaneously provides necessary information regarding breeding status of hosts and modifies breeding condition of the eavesdropper.


Assuntos
Estrogênios/metabolismo , Parasitos/metabolismo , Passeriformes/metabolismo , Animais , Feminino , Reprodução
18.
Elife ; 72018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30204084

RESUMO

The mitochondrion of apicomplexan parasites is critical for parasite survival, although the full complement of proteins that localize to this organelle has not been defined. Here we undertake two independent approaches to elucidate the mitochondrial proteome of the apicomplexan Toxoplasma gondii. We identify approximately 400 mitochondrial proteins, many of which lack homologs in the animals that these parasites infect, and most of which are important for parasite growth. We demonstrate that one such protein, termed TgApiCox25, is an important component of the parasite cytochrome c oxidase (COX) complex. We identify numerous other apicomplexan-specific components of COX, and conclude that apicomplexan COX, and apicomplexan mitochondria more generally, differ substantially in their protein composition from the hosts they infect. Our study highlights the diversity that exists in mitochondrial proteomes across the eukaryotic domain of life, and provides a foundation for defining unique aspects of mitochondrial biology in an important phylum of parasites.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Proteoma/metabolismo , Toxoplasma/metabolismo , Animais , Biotinilação , Biologia Computacional , Técnicas de Silenciamento de Genes , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Consumo de Oxigênio , Parasitos/crescimento & desenvolvimento , Parasitos/metabolismo , Fenótipo , Filogenia , Proteômica , Proteínas de Protozoários/metabolismo , Toxoplasma/crescimento & desenvolvimento
19.
Artigo em Inglês | MEDLINE | ID: mdl-30181373

RESUMO

Toxoplasma gondii is an obligate intracellular parasite that has infected one-third of the population. Upon infection of warm-blooded vertebrates, the replicating form of the parasite (tachyzoite) converts into a latent form (bradyzoite) present in tissue cysts. During immune deficiency, bradyzoites can reconvert into tachyzoites and cause life-threatening toxoplasmosis. We previously reported that translational control through phosphorylation of the α subunit of T. gondii eukaryotic initiation factor 2 (eIF2α) (TgIF2α) is a critical component of the parasite stress response. Diverse stresses can induce the conversion of tachyzoites to bradyzoites, including those disrupting the parasite's endoplasmic reticulum (ER) (ER stress). Toxoplasma possesses four eIF2α kinases, one of which (TgIF2K-A) localizes to the parasite ER analogously to protein kinase R-like endoplasmic reticulum kinase (PERK), the eIF2α kinase that responds to ER stress in mammalian cells. Here, we investigated the effects of a PERK inhibitor (PERKi) on Toxoplasma Our results show that the PERKi GSK2606414 blocks the enzymatic activity of TgIF2K-A and reduces TgIF2α phosphorylation specifically in response to ER stress. PERKi also significantly impeded multiple steps of the tachyzoite lytic cycle and sharply lowered the frequency of bradyzoite differentiation in vitro Pretreatment of host cells with PERKi prior to infection did not affect parasite infectivity, and PERKi still impaired parasite replication in host cells lacking PERK. In mice, PERKi conferred modest protection from a lethal dose of Toxoplasma Our findings represent the first pharmacological evidence supporting TgIF2K-A as an attractive new target for the treatment of toxoplasmosis.


Assuntos
Inibidores de Proteínas Quinases/farmacologia , Toxoplasma/efeitos dos fármacos , Toxoplasmose/tratamento farmacológico , eIF-2 Quinase/antagonistas & inibidores , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/parasitologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Parasitos/efeitos dos fármacos , Parasitos/metabolismo , Fosforilação/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Toxoplasmose/parasitologia
20.
PLoS Biol ; 16(9): e2005895, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30212465

RESUMO

Malaria parasites (Plasmodium spp.) and related apicomplexan pathogens contain a nonphotosynthetic plastid called the apicoplast. Derived from an unusual secondary eukaryote-eukaryote endosymbiosis, the apicoplast is a fascinating organelle whose function and biogenesis rely on a complex amalgamation of bacterial and algal pathways. Because these pathways are distinct from the human host, the apicoplast is an excellent source of novel antimalarial targets. Despite its biomedical importance and evolutionary significance, the absence of a reliable apicoplast proteome has limited most studies to the handful of pathways identified by homology to bacteria or primary chloroplasts, precluding our ability to study the most novel apicoplast pathways. Here, we combine proximity biotinylation-based proteomics (BioID) and a new machine learning algorithm to generate a high-confidence apicoplast proteome consisting of 346 proteins. Critically, the high accuracy of this proteome significantly outperforms previous prediction-based methods and extends beyond other BioID studies of unique parasite compartments. Half of identified proteins have unknown function, and 77% are predicted to be important for normal blood-stage growth. We validate the apicoplast localization of a subset of novel proteins and show that an ATP-binding cassette protein ABCF1 is essential for blood-stage survival and plays a previously unknown role in apicoplast biogenesis. These findings indicate critical organellar functions for newly discovered apicoplast proteins. The apicoplast proteome will be an important resource for elucidating unique pathways derived from secondary endosymbiosis and prioritizing antimalarial drug targets.


Assuntos
Apicoplastos/metabolismo , Biologia Computacional/métodos , Malária/metabolismo , Malária/parasitologia , Parasitos/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Proteínas de Protozoários/metabolismo , Algoritmos , Animais , Bases de Dados de Proteínas , Retículo Endoplasmático/metabolismo , Plasmodium falciparum/metabolismo
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