The coevolutionary dynamics of obligate ant social parasite systems--between prudence and antagonism.

PubMed

Brandt, Miriam; Foitzik, Susanne; Fischer-Blass, Birgit; Heinze, Jürgen

2005-05-01

In this synthesis we apply coevolutionary models to the interactions between socially parasitic ants and their hosts. Obligate social parasite systems are ideal models for coevolution, because the close phylogenetic relationship between these parasites and their hosts results in similar evolutionary potentials, thus making mutual adaptations in a stepwise fashion especially likely to occur. The evolutionary dynamics of host-parasite interactions are influenced by a number of parameters, for example the parasite's transmission mode and rate, the genetic structure of host and parasite populations, the antagonists' migration rates, and the degree of mutual specialisation. For the three types of obligate ant social parasites, queen-tolerant and queen-intolerant inquilines and slavemakers, several of these parameters, and thus the evolutionary trajectory, are likely to differ. Because of the fundamental differences in lifestyle between these social parasite systems, coevolution should further select for different traits in the parasites and their hosts. Queen-tolerant inquilines are true parasites that exert a low selection pressure on their host, because of their rarity and the fact that they do not conduct slave raids to replenish their labour force. Due to their high degree of specialisation and the potential for vertical transmission, coevolutionary theory would predict interactions between these workerless parasites and their hosts to become even more benign over time. Queen-intolerant inquilines that kill the host queen during colony take-over are best described as parasitoids, and their reproductive success is limited by the existing worker force of the invaded host nest. These parasites should therefore evolve strategies to best exploit this fixed resource. Slavemaking ants, by contrast, act as parasites only during colony foundation, while their frequent slave raids follow a predator prey dynamic. They often exploit a number of host species at a given site, and

Antisense phosphorothioate oligonucleotides: selective killing of the intracellular parasite Leishmania amazonensis.

PubMed

Ramazeilles, C; Mishra, R K; Moreau, S; Pascolo, E; Toulmé, J J

1994-08-16

We targeted the mini-exon sequence, present at the 5' end of every mRNA of the protozoan parasite Leishmania amazonensis, by phosphorothioate oligonucleotides. A complementary 16-mer (16PS) was able to kill amastigotes--the intracellular stage of the parasite--in murine macrophages in culture. After 24 hr of incubation with 10 microM 16PS, about 30% infected macrophages were cured. The oligomer 16PS acted through antisense hybridization in a sequence-dependent way; no effect on parasites was observed with noncomplementary phosphorothioate oligonucleotides. The antisense oligonucleotide 16PS was a selective killer of the protozoans without any detrimental effect to the host macrophage. Using 16PS linked to a palmitate chain, which enabled it to complex with low density lipoproteins, improved the leishmanicidal efficiency on intracellular amastigotes, probably due to increased endocytosis. Phosphorothioate oligonucleotides complementary to the intron part of the mini-exon pre-RNA were also effective, suggesting that antisense oligomers could prevent trans-splicing in these parasites.

[What makes a parasite "transforming"? Insights into cancer from the agents of an exotic pathology, Theileria spp].

PubMed

Cheeseman, K M; Weitzman, J B

2017-02-01

Theileria are obligate eukaryotic intracellular parasites of cattle. The diseases they cause, Tropical theileriosis and East Coast Fever, cause huge economic loss in East African, Mediterranean and central and South-East Asian countries. These apicomplexan parasites are the only intracellular eukaryotic parasites known to transform their host cell and represent a unique model to study host-parasite interactions and mechanisms of cancer onset.Here, we review how Theileria parasites induce transformation of their leukocyte host cell and discuss similarities with tumorigenesis. We describe how genomic innovation, epigenetic changes and hijacking of signal transductions enable a eukaryotic parasite to transform its host cell.

An obligate brood parasite trapped in the intraspecific arms race of its hosts.

PubMed

Lyon, Bruce E; Eadie, John McA

2004-11-18

Reciprocal selection pressures often lead to close and adaptive matching of traits in coevolved species. A failure of one species to match the evolutionary trajectories of another is often attributed to evolutionary lags or to differing selection pressures across a geographic mosaic. Here we show that mismatches in adaptation of interacting species--an obligate brood parasitic duck and each of its two main hosts--are best explained by the evolutionary dynamics within the host species. Rejection of the brood parasite's eggs was common by both hosts, despite a lack of detectable cost of parasitism to the hosts. Egg rejection markedly reduced parasite fitness, but egg mimicry experiments revealed no phenotypic natural selection for more mimetic parasitic eggs. These paradoxical results were resolved by the discovery of intraspecific brood parasitism and conspecific egg rejection within the hosts themselves. The apparent arms race between species seems instead to be an incidental by-product of within-species conflict, with little recourse for evolutionary response by the parasite.

Metabolic interdependence of obligate intracellular bacteria and their insect hosts.

PubMed

Zientz, Evelyn; Dandekar, Thomas; Gross, Roy

2004-12-01

Mutualistic associations of obligate intracellular bacteria and insects have attracted much interest in the past few years due to the evolutionary consequences for their genome structure. However, much less attention has been paid to the metabolic ramifications for these endosymbiotic microorganisms, which have to compete with but also to adapt to another metabolism--that of the host cell. This review attempts to provide insights into the complex physiological interactions and the evolution of metabolic pathways of several mutualistic bacteria of aphids, ants, and tsetse flies and their insect hosts.

Vertebrate Cell Cycle Modulates Infection by Protozoan Parasites

NASA Astrophysics Data System (ADS)

Dvorak, James A.; Crane, Mark St. J.

1981-11-01

Synchronized HeLa cell populations were exposed to Trypanosoma cruzi or Toxoplasma gondii, obligate intracellular protozoan parasites that cause Chagas' disease and toxoplasmosis, respectively, in humans. The ability of the two parasites to infect HeLa cells increased as the HeLa cells proceeded from the G1 phase to the S phase of their growth cycle and decreased as the cells entered G2-M. Characterization of the S-phase cell surface components responsible for this phenomenon could be beneficial in the development of vaccines against these parasitic diseases.

Optimal killing for obligate killers: the evolution of life histories and virulence of semelparous parasites.

PubMed Central

Ebert, D; Weisser, W W

1997-01-01

Many viral, bacterial and protozoan parasites of invertebrates first propagate inside their host without releasing any transmission stages and then kill their host to release all transmission stages at once. Life history and the evolution of virulence of these obligately killing parasites are modelled, assuming that within-host growth is density dependent. We find that the parasite should kill the host when its per capita growth rate falls to the level of the host mortality rate. The parasite should kill its host later when the carrying capacity, K, is higher, but should kill it earlier when the parasite-independent host mortality increases or when the parasite has a higher birth rate. When K(t), for parasite growth, is not constant over the duration of an infection, but increases with time, the parasite should kill the host around the stage when the growth rate of the carrying capacity decelerates strongly. In case that K(t) relates to host body size, this deceleration in growth is around host maturation. PMID:9263465

Leishmania donovani chaperonin 10 regulates parasite internalization and intracellular survival in human macrophages.

PubMed

Colineau, Lucie; Clos, Joachim; Moon, Kyung-Mee; Foster, Leonard J; Reiner, Neil E

2017-06-01

Protozoa of the genus Leishmania infect macrophages in their mammalian hosts causing a spectrum of diseases known as the leishmaniases. The search for leishmania effectors that support macrophage infection is a focus of significant interest. One such candidate is leishmania chaperonin 10 (CPN10) which is secreted in exosomes and may have immunosuppressive properties. Here, we report for the first time that leishmania CPN10 localizes to the cytosol of infected macrophages. Next, we generated two genetically modified strains of Leishmania donovani (Ld): one strain overexpressing CPN10 (CPN10+++) and the second, a CPN10 single allele knockdown (CPN10+/-), as the null mutant was lethal. When compared with the wild-type (WT) parental strain, CPN10+/- Ld showed higher infection rates and parasite loads in human macrophages after 24 h of infection. Conversely, CPN10+++ Ld was associated with lower initial infection rates. This unexpected apparent gain-of-function for the knockdown could have been explained either by enhanced parasite internalization or by enhanced intracellular survival. Paradoxically, we found that CPN10+/- leishmania were more readily internalized than WT Ld, but also displayed significantly impaired intracellular survival. This suggests that leishmania CPN10 negatively regulates the rate of parasite uptake by macrophages while being required for intracellular survival. Finally, quantitative proteomics identified an array of leishmania proteins whose expression was positively regulated by CPN10. In contrast, many macrophage proteins involved in innate immunity were negatively regulated by CPN10. Taken together, these findings identify leishmania CPN10 as a novel effector with broad based effects on macrophage cell regulation and parasite survival.

Gene gain and loss during evolution of obligate parasitism in the white rust pathogen of Arabidopsis thaliana.

PubMed

Kemen, Eric; Gardiner, Anastasia; Schultz-Larsen, Torsten; Kemen, Ariane C; Balmuth, Alexi L; Robert-Seilaniantz, Alexandre; Bailey, Kate; Holub, Eric; Studholme, David J; Maclean, Dan; Jones, Jonathan D G

2011-07-01

Biotrophic eukaryotic plant pathogens require a living host for their growth and form an intimate haustorial interface with parasitized cells. Evolution to biotrophy occurred independently in fungal rusts and powdery mildews, and in oomycete white rusts and downy mildews. Biotroph evolution and molecular mechanisms of biotrophy are poorly understood. It has been proposed, but not shown, that obligate biotrophy results from (i) reduced selection for maintenance of biosynthetic pathways and (ii) gain of mechanisms to evade host recognition or suppress host defence. Here we use Illumina sequencing to define the genome, transcriptome, and gene models for the obligate biotroph oomycete and Arabidopsis parasite, Albugo laibachii. A. laibachii is a member of the Chromalveolata, which incorporates Heterokonts (containing the oomycetes), Apicomplexa (which includes human parasites like Plasmodium falciparum and Toxoplasma gondii), and four other taxa. From comparisons with other oomycete plant pathogens and other chromalveolates, we reveal independent loss of molybdenum-cofactor-requiring enzymes in downy mildews, white rusts, and the malaria parasite P. falciparum. Biotrophy also requires "effectors" to suppress host defence; we reveal RXLR and Crinkler effectors shared with other oomycetes, and also discover and verify a novel class of effectors, the "CHXCs", by showing effector delivery and effector functionality. Our findings suggest that evolution to progressively more intimate association between host and parasite results in reduced selection for retention of certain biosynthetic pathways, and particularly reduced selection for retention of molybdopterin-requiring biosynthetic pathways. These mechanisms are not only relevant to plant pathogenic oomycetes but also to human pathogens within the Chromalveolata.

Gene Gain and Loss during Evolution of Obligate Parasitism in the White Rust Pathogen of Arabidopsis thaliana

PubMed Central

Kemen, Eric; Gardiner, Anastasia; Schultz-Larsen, Torsten; Kemen, Ariane C.; Balmuth, Alexi L.; Robert-Seilaniantz, Alexandre; Bailey, Kate; Holub, Eric; Studholme, David J.; MacLean, Dan; Jones, Jonathan D. G.

2011-01-01

Biotrophic eukaryotic plant pathogens require a living host for their growth and form an intimate haustorial interface with parasitized cells. Evolution to biotrophy occurred independently in fungal rusts and powdery mildews, and in oomycete white rusts and downy mildews. Biotroph evolution and molecular mechanisms of biotrophy are poorly understood. It has been proposed, but not shown, that obligate biotrophy results from (i) reduced selection for maintenance of biosynthetic pathways and (ii) gain of mechanisms to evade host recognition or suppress host defence. Here we use Illumina sequencing to define the genome, transcriptome, and gene models for the obligate biotroph oomycete and Arabidopsis parasite, Albugo laibachii. A. laibachii is a member of the Chromalveolata, which incorporates Heterokonts (containing the oomycetes), Apicomplexa (which includes human parasites like Plasmodium falciparum and Toxoplasma gondii), and four other taxa. From comparisons with other oomycete plant pathogens and other chromalveolates, we reveal independent loss of molybdenum-cofactor-requiring enzymes in downy mildews, white rusts, and the malaria parasite P. falciparum. Biotrophy also requires “effectors” to suppress host defence; we reveal RXLR and Crinkler effectors shared with other oomycetes, and also discover and verify a novel class of effectors, the “CHXCs”, by showing effector delivery and effector functionality. Our findings suggest that evolution to progressively more intimate association between host and parasite results in reduced selection for retention of certain biosynthetic pathways, and particularly reduced selection for retention of molybdopterin-requiring biosynthetic pathways. These mechanisms are not only relevant to plant pathogenic oomycetes but also to human pathogens within the Chromalveolata. PMID:21750662

Obligate brood parasites show more functionally effective innate immune responses: an eco-immunological hypothesis

USGS Publications Warehouse

Hahn, D. Caldwell; Summers, Scott G.; Genovese, Kenneth J.; He, Haiqi; Kogut, Michael H.

2013-01-01

Immune adaptations of obligate brood parasites attracted interest when three New World cowbird species (Passeriformes, Icteridae, genus Molothrus) proved unusually resistant to West Nile virus. We have used cowbirds as models to investigate the eco-immunological hypothesis that species in parasite-rich environments characteristically have enhanced immunity as a life history adaptation. As part of an ongoing program to understand the cowbird immune system, in this study we measured degranulation and oxidative burst, two fundamental responses of the innate immune system. Innate immunity provides non-specific, fast-acting defenses against a variety of invading pathogens, and we hypothesized that innate immunity experiences particularly strong selection in cowbirds, because their life history strategy exposes them to diverse novel and unpredictable parasites. We compared the relative effectiveness of degranulation and oxidative burst responses in two cowbird species and one related, non-parasitic species. Both innate immune defenses were significantly more functionally efficient in the two parasitic cowbird species than in the non-parasitic red-winged blackbird (Icteridae, Agelaius phoeniceus). Additionally, both immune defenses were more functionally efficient in the brown-headed cowbird (M. ater), an extreme host-generalist brood parasite, than in the bronzed cowbird (M. aeneus), a moderate host-specialist with lower exposure to other species and their parasites. Thus the relative effectiveness of these two innate immune responses corresponds to the diversity of parasites in the niche of each species and to their relative resistance to WNV. This study is the first use of these two specialized assays in a comparative immunology study of wild avian species.

Proteome of Aedes aegypti in response to infection and coinfection with microsporidian parasites

PubMed Central

Duncan, Alison B; Agnew, Philip; Noel, Valérie; Demettre, Edith; Seveno, Martial; Brizard, Jean-Paul; Michalakis, Yannis

2012-01-01

Hosts are frequently infected with more than one parasite or pathogen at any one time, but little is known as to how they respond to multiple immune challenges compared to those involving single infections. We investigated the proteome of Aedes aegypti larvae following infection with either Edhazardia aedis or Vavraia culicis, and coinfections involving both. They are both obligate intracellular parasites belonging to the phylum microsporidia and infect natural populations of Ae. aegypti. The results found some proteins only showing modified abundance in response to infections involving E. aedis, while others were only differentially abundant when infections involved V. culicis. Some proteins only responded with modified abundance to the coinfection condition, while others were differentially abundant in response to all three types of infection. As time since infection increased, the response to each of the single parasite infections diverged, while the response to the E. aedis and coinfection treatments converged. Some of the proteins differentially abundant in response to infection were identified. They included two vacuolar ATPases, proteins known to have a role in determining the infection success of intracellular parasites. This result suggests microsporidia could influence the infection success of other intracellular pathogens infecting vector species of mosquito, including viruses, Plasmodium and Wolbachia. PMID:22837817

Toxoplasma gondii Relies on Both Host and Parasite Isoprenoids and Can Be Rendered Sensitive to Atorvastatin

PubMed Central

Li, Zhu-Hong; Ramakrishnan, Srinivasan; Striepen, Boris; Moreno, Silvia N. J.

2013-01-01

Intracellular pathogens have complex metabolic interactions with their host cells to ensure a steady supply of energy and anabolic building blocks for rapid growth. Here we use the obligate intracellular parasite Toxoplasma gondii to probe this interaction for isoprenoids, abundant lipidic compounds essential to many cellular processes including signaling, trafficking, energy metabolism, and protein translation. Synthesis of precursors for isoprenoids in Apicomplexa occurs in the apicoplast and is essential. To synthesize longer isoprenoids from these precursors, T. gondii expresses a bifunctional farnesyl diphosphate/geranylgeranyl diphosphate synthase (TgFPPS). In this work we construct and characterize T. gondii null mutants for this enzyme. Surprisingly, these mutants have only a mild growth phenotype and an isoprenoid composition similar to wild type parasites. However, when extracellular, the loss of the enzyme becomes phenotypically apparent. This strongly suggests that intracellular parasite salvage FPP and/or geranylgeranyl diphosphate (GGPP) from the host. We test this hypothesis using inhibitors of host cell isoprenoid synthesis. Mammals use the mevalonate pathway, which is susceptible to statins. We document strong synergy between statin treatment and pharmacological or genetic interference with the parasite isoprenoid pathway. Mice can be cured with atorvastatin (Lipitor) from a lethal infection with the TgFPPs mutant. We propose a double-hit strategy combining inhibitors of host and parasite pathways as a novel therapeutic approach against Apicomplexan parasites. PMID:24146616

Toxoplasma gondii relies on both host and parasite isoprenoids and can be rendered sensitive to atorvastatin.

PubMed

Li, Zhu-Hong; Ramakrishnan, Srinivasan; Striepen, Boris; Moreno, Silvia N J

2013-01-01

Intracellular pathogens have complex metabolic interactions with their host cells to ensure a steady supply of energy and anabolic building blocks for rapid growth. Here we use the obligate intracellular parasite Toxoplasma gondii to probe this interaction for isoprenoids, abundant lipidic compounds essential to many cellular processes including signaling, trafficking, energy metabolism, and protein translation. Synthesis of precursors for isoprenoids in Apicomplexa occurs in the apicoplast and is essential. To synthesize longer isoprenoids from these precursors, T. gondii expresses a bifunctional farnesyl diphosphate/geranylgeranyl diphosphate synthase (TgFPPS). In this work we construct and characterize T. gondii null mutants for this enzyme. Surprisingly, these mutants have only a mild growth phenotype and an isoprenoid composition similar to wild type parasites. However, when extracellular, the loss of the enzyme becomes phenotypically apparent. This strongly suggests that intracellular parasite salvage FPP and/or geranylgeranyl diphosphate (GGPP) from the host. We test this hypothesis using inhibitors of host cell isoprenoid synthesis. Mammals use the mevalonate pathway, which is susceptible to statins. We document strong synergy between statin treatment and pharmacological or genetic interference with the parasite isoprenoid pathway. Mice can be cured with atorvastatin (Lipitor) from a lethal infection with the TgFPPs mutant. We propose a double-hit strategy combining inhibitors of host and parasite pathways as a novel therapeutic approach against Apicomplexan parasites.

Use of flow cytometry and PCR analysis to detect 5-carboxyfluoroscein-stained obligate intracellular bacteria Lawsonia intracellularis invasion of McCoy cells.

PubMed

Obradovic, Milan; Pasternak, J Alex; Ng, Siew Hon; Wilson, Heather L

2016-07-01

In this study, we describe a method to quantify invasion of obligate intracellular bacteria, Lawsonia intracellularis, inside McCoy cells. In immunological research, the cell-permeable fluorescent dye 5'-carboxyfluoroscein succidyl ester (CFSE) is commonly used to quantify eukaryotic cellular proliferation. Instead of using it in this traditional way, we stained L. intracellularis with CFSE dye prior to infection of McCoy cells. Flow cytometry was performed to quantify the percentage of eukaryotic cells which had taken up or were associated with fluorescent bacteria. As obligate intracellular bacteria, they cannot replicate outside of eukaryotic cells and thus qPCR analysis was used to quantify bacterial growth. Indirectly, PCR analysis confirmed invasion rather than adherence to the McCoy cell surface. Fluorescent activated cell sorting (FACS) was used to sort the CFSE(+) (i.e. infected) McCoy cells from the CFSE(-) (i.e. non-infected) McCoy cells and confocal microscopy was used to confirm bacterial invasion and cytosolic localization of CFSE-L. intracellularis. To show that this approach could be used in conjunction with functional assays, we investigated the effect that serum antibodies had on CFSE-bacterial invasion and growth. Instead of blocking invasion, rabbit hyperimmune serum augmented invasion of the bacteria inside McCoy cells and qPCR analysis confirmed bacterial growth over the course of 5days. We conclude that CFSE-labeling of bacteria and qPCR can be used to track and quantify bacterial invasion and may be a valuable tool for studying the invasive properties of bacteria, especially if commercial antibodies are not available. This approach may be adapted for use in other obligate intracellular bacteria and intracellular pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Induction of dendritic cell migration upon Toxoplasma gondii infection potentiates parasite dissemination.

PubMed

Lambert, Henrik; Hitziger, Niclas; Dellacasa, Isabel; Svensson, Mattias; Barragan, Antonio

2006-10-01

The processes leading to systemic dissemination of the obligate intracellular parasite Toxoplasma gondii remain unelucidated. In vitro studies on human and murine dendritic cells (DC) revealed that active invasion of DC by Toxoplasma induces a state of hypermotility in DC, enabling transmigration of infected DC across endothelial cell monolayers in the absence of chemotactic stimuli. Infected DC exhibited upregulation of maturation markers and co-stimulatory molecules. While modulation of cell adhesion molecules CD11/CD18 was similar for Toxoplasma-infected DC and lipopolysaccharide (LPS)-matured DC, Toxoplasma-infected DC did not exhibit upregulation of CD54/ICAM-1. Induction of host cell migration in vitro required live intracellular parasite(s) and was inhibited by uncoupling the Gi-protein signalling pathway with pertussis toxin, but did not depend on CCR5, CCR7 or Toll/interleukin-1 receptor signalling. When migration of Toxoplasma-infected DC was compared with migration of LPS-stimulated DC in vivo, similar or higher numbers of Toxoplasma-infected DC reached the mesenteric lymph nodes and spleen respectively. Adoptive transfer of Toxoplasma-infected DC resulted in more rapid dissemination of parasites to distant organs and in exacerbation of infection compared with inoculation with free parasites. Altogether, these findings show that Toxoplasma is able to subvert the regulation of host cell motility and likely exploits the host's natural pathways of cellular migration for parasite dissemination.

Shared elements of host-targeting pathways among apicomplexan parasites of differing lifestyles.

PubMed

Pellé, Karell G; Jiang, Rays H Y; Mantel, Pierre-Yves; Xiao, Yu-Ping; Hjelmqvist, Daisy; Gallego-Lopez, Gina M; O T Lau, Audrey; Kang, Byung-Ho; Allred, David R; Marti, Matthias

2015-11-01

Apicomplexans are a diverse group of obligate parasites occupying different intracellular niches that require modification to meet the needs of the parasite. To efficiently manipulate their environment, apicomplexans translocate numerous parasite proteins into the host cell. Whereas some parasites remain contained within a parasitophorous vacuole membrane (PVM) throughout their developmental cycle, others do not, a difference that affects the machinery needed for protein export. A signal-mediated pathway for protein export into the host cell has been characterized in Plasmodium parasites, which maintain the PVM. Here, we functionally demonstrate an analogous host-targeting pathway involving organellar staging prior to secretion in the related bovine parasite, Babesia bovis, a parasite that destroys the PVM shortly after invasion. Taking into account recent identification of a similar signal-mediated pathway in the coccidian parasite Toxoplasma gondii, we suggest a model in which this conserved pathway has evolved in multiple steps from signal-mediated trafficking to specific secretory organelles for controlled secretion to a complex protein translocation process across the PVM. © 2015 John Wiley & Sons Ltd.

Innovative approach for transcriptomic analysis of obligate intracellular pathogen: selective capture of transcribed sequences of Ehrlichia ruminantium

PubMed Central

2009-01-01

Background Whole genome transcriptomic analysis is a powerful approach to elucidate the molecular mechanisms controlling the pathogenesis of obligate intracellular bacteria. However, the major hurdle resides in the low quantity of prokaryotic mRNAs extracted from host cells. Our model Ehrlichia ruminantium (ER), the causative agent of heartwater, is transmitted by tick Amblyomma variegatum. This bacterium affects wild and domestic ruminants and is present in Sub-Saharan Africa and the Caribbean islands. Because of its strictly intracellular location, which constitutes a limitation for its extensive study, the molecular mechanisms involved in its pathogenicity are still poorly understood. Results We successfully adapted the SCOTS method (Selective Capture of Transcribed Sequences) on the model Rickettsiales ER to capture mRNAs. Southern Blots and RT-PCR revealed an enrichment of ER's cDNAs and a diminution of ribosomal contaminants after three rounds of capture. qRT-PCR and whole-genome ER microarrays hybridizations demonstrated that SCOTS method introduced only a limited bias on gene expression. Indeed, we confirmed the differential gene expression between poorly and highly expressed genes before and after SCOTS captures. The comparative gene expression obtained from ER microarrays data, on samples before and after SCOTS at 96 hpi was significantly correlated (R2 = 0.7). Moreover, SCOTS method is crucial for microarrays analysis of ER, especially for early time points post-infection. There was low detection of transcripts for untreated samples whereas 24% and 70.7% were revealed for SCOTS samples at 24 and 96 hpi respectively. Conclusions We conclude that this SCOTS method has a key importance for the transcriptomic analysis of ER and can be potentially used for other Rickettsiales. This study constitutes the first step for further gene expression analyses that will lead to a better understanding of both ER pathogenicity and the adaptation of obligate intracellular

The moving junction of apicomplexan parasites: a key structure for invasion.

PubMed

Besteiro, Sébastien; Dubremetz, Jean-François; Lebrun, Maryse

2011-06-01

Most Apicomplexa are obligate intracellular parasites and many are important pathogens of human and domestic animals. For a successful cell invasion, they rely on their own motility and on a firm anchorage to their host cell, depending on the secretion of proteins and the establishment of a structure called the moving junction (MJ). The MJ moves from the apical to the posterior end of the parasite, leading to the internalization of the parasite into a parasitophorous vacuole. Based on recent data obtained in Plasmodium and Toxoplasma, an emerging model emphasizes a cooperative role of secreted parasitic proteins in building the MJ and driving this crucial invasive process. More precisely, the parasite exports the microneme protein AMA1 to its own surface and the rhoptry neck RON2 protein as a receptor inserted into the host cell together with other RON partners. Ongoing and future research will certainly help refining the model by characterizing the molecular organization within the MJ and its interactions with both host and parasite cytoskeleton for anchoring of the complex. © 2011 Blackwell Publishing Ltd.

Apicoplast and Endoplasmic Reticulum Cooperate in Fatty Acid Biosynthesis in Apicomplexan Parasite Toxoplasma gondii*

PubMed Central

Ramakrishnan, Srinivasan; Docampo, Melissa D.; MacRae, James I.; Pujol, François M.; Brooks, Carrie F.; van Dooren, Giel G.; Hiltunen, J. Kalervo; Kastaniotis, Alexander J.; McConville, Malcolm J.; Striepen, Boris

2012-01-01

Apicomplexan parasites are responsible for high impact human diseases such as malaria, toxoplasmosis, and cryptosporidiosis. These obligate intracellular pathogens are dependent on both de novo lipid biosynthesis as well as the uptake of host lipids for biogenesis of parasite membranes. Genome annotations and biochemical studies indicate that apicomplexan parasites can synthesize fatty acids via a number of different biosynthetic pathways that are differentially compartmentalized. However, the relative contribution of each of these biosynthetic pathways to total fatty acid composition of intracellular parasite stages remains poorly defined. Here, we use a combination of genetic, biochemical, and metabolomic approaches to delineate the contribution of fatty acid biosynthetic pathways in Toxoplasma gondii. Metabolic labeling studies with [13C]glucose showed that intracellular tachyzoites synthesized a range of long and very long chain fatty acids (C14:0–26:1). Genetic disruption of the apicoplast-localized type II fatty-acid synthase resulted in greatly reduced synthesis of saturated fatty acids up to 18 carbons long. Ablation of type II fatty-acid synthase activity resulted in reduced intracellular growth that was partially restored by addition of long chain fatty acids. In contrast, synthesis of very long chain fatty acids was primarily dependent on a fatty acid elongation system comprising three elongases, two reductases, and a dehydratase that were localized to the endoplasmic reticulum. The function of these enzymes was confirmed by heterologous expression in yeast. This elongase pathway appears to have a unique role in generating very long unsaturated fatty acids (C26:1) that cannot be salvaged from the host. PMID:22179608

Invasion of host cells by malaria parasites: a tale of two protein families.

PubMed

Iyer, Jayasree; Grüner, Anne Charlotte; Rénia, Laurent; Snounou, Georges; Preiser, Peter R

2007-07-01

Malaria parasites are obligate intracellular parasites whose invasive stages select and invade the unique host cell in which they can develop with exquisite specificity and efficacy. Most studies aimed at elucidating the molecules and the mechanisms implicated in the selection and invasion processes have been conducted on the merozoite, the stage that invades erythrocytes to perpetuate the pathological cycles of parasite multiplication in the blood. Bioinformatic analysis has helped identify the members of two parasite protein families, the reticulocyte-binding protein homologues (RBL) and erythrocyte binding like (EBL), in recently sequenced genomes of different Plasmodium species. In this article we review data from classical studies and gene disruption experiments that are helping to illuminate the role of these proteins in the selection-invasion processes. The manner in which subsets of proteins from each of the families act in concert suggests a model to explain the ability of the parasites to use alternate pathways of invasion. Future perspectives and implications are discussed.

Parasitism and mutualism in Wolbachia: what the phylogenomic trees can and cannot say.

PubMed

Bordenstein, Seth R; Paraskevopoulos, Charalampos; Dunning Hotopp, Julie C; Sapountzis, Panagiotis; Lo, Nathan; Bandi, Claudio; Tettelin, Hervé; Werren, John H; Bourtzis, Kostas

2009-01-01

Ecological and evolutionary theories predict that parasitism and mutualism are not fixed endpoints of the symbiotic spectrum. Rather, parasitism and mutualism may be host or environment dependent, induced by the same genetic machinery, and shifted due to selection. These models presume the existence of genetic or environmental variation that can spur incipient changes in symbiotic lifestyle. However, for obligate intracellular bacteria whose genomes are highly reduced, studies specify that discrete symbiotic associations can be evolutionarily stable for hundreds of millions of years. Wolbachia is an inherited obligate, intracellular infection of invertebrates containing taxa that act broadly as both parasites in arthropods and mutualists in certain roundworms. Here, we analyze the ancestry of mutualism and parasitism in Wolbachia and the evolutionary trajectory of this variation in symbiotic lifestyle with a comprehensive, phylogenomic analysis. Contrary to previous claims, we show unequivocally that the transition in lifestyle cannot be reconstructed with current methods due to long-branch attraction (LBA) artifacts of the distant Anaplasma and Ehrlichia outgroups. Despite the use of 1) site-heterogenous phylogenomic methods that can overcome systematic error, 2) a taxonomically rich set of taxa, and 3) statistical assessments of the genes, tree topologies, and models of evolution, we conclude that the LBA artifact is serious enough to afflict past and recent claims including the root lies in the middle of the Wolbachia mutualists and parasites. We show that different inference methods yield different results and high bootstrap support did not equal phylogenetic accuracy. Recombination was rare among this taxonomically diverse data set, indicating that elevated levels of recombination in Wolbachia are restricted to specific coinfecting groups. In conclusion, we attribute the inability to root the tree to rate heterogeneity between the ingroup and outgroup. Site

Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.

PubMed

Soeiro, M N C; Werbovetz, K; Boykin, D W; Wilson, W D; Wang, M Z; Hemphill, A

2013-07-01

Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates.

Novel amidines and analogues as promising agents against intracellular parasites: a systematic review

PubMed Central

Soeiro, M. N. C.; Werbovetz, K.; Boykin, D.W.; Wilson, W. D.; Wang, M. Z.; Hemphill, A.

2013-01-01

SUMMARY Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates. PMID:23561006

Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

PubMed

Kumari, Anjali; Singh, Krishn Pratap; Mandal, Abhishek; Paswan, Ranjeet Kumar; Sinha, Preeti; Das, Pradeep; Ali, Vahab; Bimal, Sanjiva; Lal, Chandra Shekhar

2017-01-01

Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) and Zinc Sulfate (ZnSO4). Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death. Therefore, cellular

Mice deficient in LRG-47 display enhanced susceptibility to Trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth.

PubMed

Santiago, Helton C; Feng, Carl G; Bafica, Andre; Roffe, Ester; Arantes, Rosa M; Cheever, Allen; Taylor, Gregory; Vieira, Leda Q; Vierira, Leda Q; Aliberti, Julio; Gazzinelli, Ricardo T; Sher, Alan

2005-12-15

IFN-gamma is known to be required for host control of intracellular Trypanosoma cruzi infection in mice, although the basis of its protective function is poorly understood. LRG-47 is an IFN-inducible p47GTPase that has been shown to regulate host resistance to intracellular pathogens. To investigate the possible role of LRG-47 in IFN-gamma-dependent control of T. cruzi infection, LRG-47 knockout (KO) and wild-type (WT) mice were infected with the Y strain of this parasite, and host responses were analyzed. When assayed on day 12 after parasite inoculation, LRG-47 KO mice, in contrast to IFN-gamma KO mice, controlled early parasitemia almost as effectively as WT animals. However, the infected LRG-47 KO mice displayed a rebound in parasite growth on day 15, and all succumbed to the infection by day 19. Additional analysis indicated that LRG-47-deficient mice exhibit unimpaired proinflammatory responses throughout the infection. Instead, reactivated disease in the KO animals was associated with severe splenic and thymic atrophy, anemia, and thrombocytopenia not observed in their WT counterparts. In addition, in vitro studies revealed that IFN-gamma-stimulated LRG-47 KO macrophages display defective intracellular killing of amastigotes despite normal expression of TNF and NO synthetase type 2 and that both NO synthetase type 2 and LRG-47 are required for optimum IFN-gamma-dependent restriction of parasite growth. Together, these data establish that LRG-47 can influence pathogen control by simultaneously regulating macrophage-microbicidal activity and hemopoietic function.

Surveillance of parasitic Legionella in surface waters by using immunomagnetic separation and amoebae enrichment

PubMed Central

Hsu, Tsui-Kang; Wu, Shu-Fen; Hsu, Bing-Mu; Kao, Po-Min; Tao, Chi-Wei; Shen, Shu-Min; Ji, Wen-Tsai; Huang, Wen-Chien; Fan, Cheng-Wei

2015-01-01

Free-living amoebae (FLA) are potential reservoirs of Legionella in aquatic environments. However, the parasitic relationship between various Legionella and amoebae remains unclear. In this study, surface water samples were gathered from two rivers for evaluating parasitic Legionella. Warmer water temperature is critical to the existence of Legionella. This result suggests that amoebae may be helpful in maintaining Legionella in natural environments because warmer temperatures could enhance parasitisation of Legionella in amoebae. We next used immunomagnetic separation (IMS) to identify extracellular Legionella and remove most free Legionella before detecting the parasitic ones in selectively enriched amoebae. Legionella pneumophila was detected in all the approaches, confirming that the pathogen is a facultative amoebae parasite. By contrast, two obligate amoebae parasites, Legionella-like amoebal pathogens (LLAPs) 8 and 9, were detected only in enriched amoebae. However, several uncultured Legionella were detected only in the extracellular samples. Because the presence of potential hosts, namely Vermamoeba vermiformis, Acanthamoeba spp. and Naegleria gruberi, was confirmed in the samples that contained intracellular Legionella, uncultured Legionella may survive independently of amoebae. Immunomagnetic separation and amoebae enrichment may have referential value for detecting parasitic Legionella in surface waters. PMID:26373823

Surveillance of parasitic Legionella in surface waters by using immunomagnetic separation and amoebae enrichment.

PubMed

Hsu, Tsui-Kang; Wu, Shu-Fen; Hsu, Bing-Mu; Kao, Po-Min; Tao, Chi-Wei; Shen, Shu-Min; Ji, Wen-Tsai; Huang, Wen-Chien; Fan, Cheng-Wei

2015-01-01

Free-living amoebae (FLA) are potential reservoirs of Legionella in aquatic environments. However, the parasitic relationship between various Legionella and amoebae remains unclear. In this study, surface water samples were gathered from two rivers for evaluating parasitic Legionella. Warmer water temperature is critical to the existence of Legionella. This result suggests that amoebae may be helpful in maintaining Legionella in natural environments because warmer temperatures could enhance parasitisation of Legionella in amoebae. We next used immunomagnetic separation (IMS) to identify extracellular Legionella and remove most free Legionella before detecting the parasitic ones in selectively enriched amoebae. Legionella pneumophila was detected in all the approaches, confirming that the pathogen is a facultative amoebae parasite. By contrast, two obligate amoebae parasites, Legionella-like amoebal pathogens (LLAPs) 8 and 9, were detected only in enriched amoebae. However, several uncultured Legionella were detected only in the extracellular samples. Because the presence of potential hosts, namely Vermamoeba vermiformis, Acanthamoeba spp. and Naegleria gruberi, was confirmed in the samples that contained intracellular Legionella, uncultured Legionella may survive independently of amoebae. Immunomagnetic separation and amoebae enrichment may have referential value for detecting parasitic Legionella in surface waters.

Recent progress in understanding host immune response to Avian Coccidiosis: Th1 and Th17 responses

USDA-ARS?s Scientific Manuscript database

Host-pathogen interaction leading to protection against coccidiosis is complex, involving many aspects of innate and adaptive immunity to intracellular parasites. The etiologic agent of avian coccidiosis is Eimeria, a genus of eukaryotic obligate intracellular parasites belonging to the phylum Apico...

Free-Living Amoebae as Hosts for and Vectors of Intracellular Microorganisms with Public Health Significance.

PubMed

Balczun, Carsten; Scheid, Patrick L

2017-04-01

Free-living amoebae (FLA) are parasites within both humans and animals causing a wide range of symptoms and act as hosts of, and vehicles for phylogenetically diverse microorganisms, called endocytobionts. The interaction of the FLA with sympatric microorganisms leads to an exceptional diversity within FLA. Some of these bacteria, viruses, and even eukaryotes, can live and replicate intracellularly within the FLA. This relationship provides protection to the microorganisms from external interventions and a dispersal mechanism across various habitats. Among those intracellularly-replicating or -residing organisms there are obligate and facultative pathogenic microorganisms affecting the health of humans or animals and are therefore of interest to Public Health Authorities. Mimiviruses, Pandoraviruses, and Pithoviruses are examples for interesting viral endocytobionts within FLA. Future research is expected to reveal further endocytobionts within free-living amoebae and other protozoa through co-cultivation studies, genomic, transcriptomic, and proteomic analyses.

Free-Living Amoebae as Hosts for and Vectors of Intracellular Microorganisms with Public Health Significance

PubMed Central

Balczun, Carsten; Scheid, Patrick L.

2017-01-01

Free-living amoebae (FLA) are parasites within both humans and animals causing a wide range of symptoms and act as hosts of, and vehicles for phylogenetically diverse microorganisms, called endocytobionts. The interaction of the FLA with sympatric microorganisms leads to an exceptional diversity within FLA. Some of these bacteria, viruses, and even eukaryotes, can live and replicate intracellularly within the FLA. This relationship provides protection to the microorganisms from external interventions and a dispersal mechanism across various habitats. Among those intracellularly-replicating or -residing organisms there are obligate and facultative pathogenic microorganisms affecting the health of humans or animals and are therefore of interest to Public Health Authorities. Mimiviruses, Pandoraviruses, and Pithoviruses are examples for interesting viral endocytobionts within FLA. Future research is expected to reveal further endocytobionts within free-living amoebae and other protozoa through co-cultivation studies, genomic, transcriptomic, and proteomic analyses. PMID:28368313

Genus-specific PCR Primers Targeting Intracellular Parasite Euduboscquella (Dinoflagellata: Syndinea)

NASA Astrophysics Data System (ADS)

Jung, Jae-Ho; Choi, Jung Min; Kim, Young-Ok

2018-03-01

We designed a genus-specific primer pair targeting the intracellular parasite Euduboscquella. To increase target specificity and inhibit untargeted PCR, two nucleotides were added at the 3' end of the reverse primer, one being a complementary nucleotide to the Euduboscquella-specific SNP (single-nucleotide polymorphism) and the other a deliberately mismatched nucleotide. Target specificity of the primer set was verified experimentally using PCR of two Euduboscquella species (positive controls) and 15 related species (negative controls composed of ciliates, diatoms and dinoflagellates), and analytical comparison with SILVA SSU rRNA gene database (release 119) in silico. In addition, we applied the Euduboscquella-specific primer set to four environmental samples previously determined by cytological staining to be either positive or negative for Euduboscquella. As expected, only positive controls and environmental samples known to contain Euduboscquella were successfully amplified by the primer set. An inferred SSU rRNA gene phylogeny placed environmental samples containing aloricate ciliates infected by Euduboscquella in a cluster discrete from Euduboscquella groups a-d previously reported from loricate, tintinnid ciliates.

Sugar nucleotide quantification by liquid chromatography tandem mass spectrometry reveals a distinct profile in Plasmodium falciparum sexual stage parasites

PubMed Central

López-Gutiérrez, Borja; Dinglasan, Rhoel R.

2017-01-01

The obligate intracellular lifestyle of Plasmodium falciparum and the difficulties in obtaining sufficient amounts of biological material have hampered the study of specific metabolic pathways in the malaria parasite. Thus, for example, the pools of sugar nucleotides required to fuel glycosylation reactions have never been studied in-depth in well-synchronized asexual parasites or in other stages of its life cycle. These metabolites are of critical importance, especially considering the renewed interest in the presence of N-, O-, and other glycans in key parasite proteins. In this work, we adapted a liquid chromatography tandem mass spectrometry (LC-MS/MS) method based on the use of porous graphitic carbon (PGC) columns and MS-friendly solvents to quantify sugar nucleotides in the malaria parasite. We report the thorough quantification of the pools of these metabolites throughout the intraerythrocytic cycle of P. falciparum. The sensitivity of the method enabled, for the first time, the targeted analysis of these glycosylation precursors in gametocytes, the parasite sexual stages that are transmissible to the mosquito vector. PMID:28104756

Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life

PubMed Central

Gillespie, Joseph J.; Williams, Kelly; Shukla, Maulik; Snyder, Eric E.; Nordberg, Eric K.; Ceraul, Shane M.; Dharmanolla, Chitti; Rainey, Daphne; Soneja, Jeetendra; Shallom, Joshua M.; Vishnubhat, Nataraj Dongre; Wattam, Rebecca; Purkayastha, Anjan; Czar, Michael; Crasta, Oswald; Setubal, Joao C.; Azad, Abdu F.; Sobral, Bruno S.

2008-01-01

Background Completed genome sequences are rapidly increasing for Rickettsia, obligate intracellular α-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs). Methodology/Principal Findings We present 1823 representative (no gene duplications) and 259 non-representative (at least one gene duplication) rickettsial OGs. While the highly reductive (∼1.2 MB) Rickettsia genomes range in predicted ORFs from 872 to 1512, a core of 752 OGs was identified, depicting the essential Rickettsia genes. Unsurprisingly, this core lacks many metabolic genes, reflecting the dependence on host resources for growth and survival. Additionally, we bolster our recent reclassification of Rickettsia by identifying OGs that define the AG (ancestral group), TG (typhus group), TRG (transitional group), and SFG (spotted fever group) rickettsiae. OGs for insect-associated species, tick-associated species and species that harbor plasmids were also predicted. Through superimposition of all OGs over robust phylogeny estimation, we discern between C1OGs and C2OGs, the latter depicting genes either decaying from the conserved C1OGs or acquired laterally. Finally, scrutiny of non-representative OGs revealed high levels of split genes versus gene duplications, with both phenomena confounding gene orthology assignment. Interestingly, non-representative OGs, as well as OGs comprised of several gene families typically involved in microbial pathogenicity and/or the acquisition of virulence factors, fall predominantly within C2OG distributions. Conclusion/Significance Collectively, we determined the relative conservation and distribution of 14354 predicted

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii.

PubMed

Lun, Zhao-Rong; Lai, De-Hua; Wen, Yan-Zi; Zheng, Ling-Ling; Shen, Ji-Long; Yang, Ting-Bo; Zhou, Wen-Liang; Qu, Liang-Hu; Hide, Geoff; Ayala, Francisco J

2015-07-21

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

PubMed Central

Lun, Zhao-Rong; Lai, De-Hua; Wen, Yan-Zi; Zheng, Ling-Ling; Shen, Ji-Long; Yang, Ting-Bo; Zhou, Wen-Liang; Qu, Liang-Hu; Hide, Geoff; Ayala, Francisco J.

2015-01-01

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias. PMID:26195778

Amastin Knockdown in Leishmania braziliensis Affects Parasite-Macrophage Interaction and Results in Impaired Viability of Intracellular Amastigotes.

PubMed

de Paiva, Rita Marcia Cardoso; Grazielle-Silva, Viviane; Cardoso, Mariana Santos; Nakagaki, Brenda Naemi; Mendonça-Neto, Rondon Pessoa; Canavaci, Adriana Monte Cassiano; Souza Melo, Normanda; Martinelli, Patrícia Massara; Fernandes, Ana Paula; daRocha, Wanderson Duarte; Teixeira, Santuza M R

2015-12-01

Leishmaniasis, a human parasitic disease with manifestations ranging from cutaneous ulcerations to fatal visceral infection, is caused by several Leishmania species. These protozoan parasites replicate as extracellular, flagellated promastigotes in the gut of a sandfly vector and as amastigotes inside the parasitophorous vacuole of vertebrate host macrophages. Amastins are surface glycoproteins encoded by large gene families present in the genomes of several trypanosomatids and highly expressed in the intracellular amastigote stages of Trypanosoma cruzi and Leishmania spp. Here, we showed that the genome of L. braziliensis contains 52 amastin genes belonging to all four previously described amastin subfamilies and that the expression of members of all subfamilies is upregulated in L. braziliensis amastigotes. Although primary sequence alignments showed no homology to any known protein sequence, homology searches based on secondary structure predictions indicate that amastins are related to claudins, a group of proteins that are components of eukaryotic tight junction complexes. By knocking-down the expression of δ-amastins in L. braziliensis, their essential role during infection became evident. δ-amastin knockdown parasites showed impaired growth after in vitro infection of mouse macrophages and completely failed to produce infection when inoculated in BALB/c mice, an attenuated phenotype that was reverted by the re-expression of an RNAi-resistant amastin gene. Further highlighting their essential role in host-parasite interactions, electron microscopy analyses of macrophages infected with amastin knockdown parasites showed significant alterations in the tight contact that is normally observed between the surface of wild type amastigotes and the membrane of the parasitophorous vacuole.

[Parasites and cancer: is there a causal link?

PubMed

Cheeseman, Kevin; Certad, Gabriela; Weitzman, Jonathan B

2016-10-01

Over 20 % of cancers have infectious origins, including well-known examples of microbes such as viruses (HPV, EBV) and bacteria (H. pylori). The contribution of intracellular eukaryotic parasites to cancer etiology is largely unexplored. Epidemiological and clinical reports indicate that eukaryotic protozoan, such as intracellular apicomplexan that cause diseases of medical or economic importance, can be linked to various cancers: Theileria and Cryptosporidium induce host cell transformation while Plasmodium was linked epidemiologically to the "African lymphoma belt" over fifty years ago. These intracellular eukaryotic parasites hijack cellular pathways to manipulate the host cell epigenome, cellular machinery, signaling pathways and epigenetic programs and marks, such as methylation and acetylation, for their own benefit. In doing so, they tinker with the same pathways as those deregulated during cancer onset. Here we discuss how epidemiological evidence linking eukaryotic intracellular parasites to cancer onset are further strengthened by recent mechanistic studies in three apicomplexan parasites. © 2016 médecine/sciences – Inserm.

Evolution of Caenorhabditis elegans host defense under selection by the bacterial parasite Serratia marcescens.

PubMed

Penley, McKenna J; Ha, Giang T; Morran, Levi T

2017-01-01

Parasites can impose strong selection on hosts. In response, some host populations have adapted via the evolution of defenses that prevent or impede infection by parasites. However, host populations have also evolved life history shifts that maximize host fitness despite infection. Outcrossing and self-fertilization can have contrasting effects on evolutionary trajectories of host populations. While selfing and outcrossing are known to affect the rate at which host populations adapt in response to parasites, these mating systems may also influence the specific traits that underlie adaptation to parasites. Here, we determined the role of evolved host defense versus altered life history,in mixed mating (selfing and outcrossing) and obligately outcrossing C. elegans host populations after experimental evolution with the bacterial parasite, S. marcescens. Similar to previous studies, we found that both mixed mating and obligately outcrossing host populations adapted to S. marcescens exposure, and that the obligately outcrossing populations exhibited the greatest rates of adaptation. Regardless of the host population mating system, exposure to parasites did not significantly alter reproductive timing or total fecundity over the course of experimental evolution. However, both mixed mating and obligately outcrossing host populations exhibited significantly reduced mortality rates in the presence of the parasite after experimental evolution. Therefore, adaptation in both the mixed mating and obligately outcrossing populations was driven, at least in part, by the evolution of increased host defense and not changes in host life history. Thus, the host mating system altered the rate of adaptation, but not the nature of adaptive change in the host populations.

Evolution of Caenorhabditis elegans host defense under selection by the bacterial parasite Serratia marcescens

PubMed Central

Penley, McKenna J.; Ha, Giang T.; Morran, Levi T.

2017-01-01

Parasites can impose strong selection on hosts. In response, some host populations have adapted via the evolution of defenses that prevent or impede infection by parasites. However, host populations have also evolved life history shifts that maximize host fitness despite infection. Outcrossing and self-fertilization can have contrasting effects on evolutionary trajectories of host populations. While selfing and outcrossing are known to affect the rate at which host populations adapt in response to parasites, these mating systems may also influence the specific traits that underlie adaptation to parasites. Here, we determined the role of evolved host defense versus altered life history,in mixed mating (selfing and outcrossing) and obligately outcrossing C. elegans host populations after experimental evolution with the bacterial parasite, S. marcescens. Similar to previous studies, we found that both mixed mating and obligately outcrossing host populations adapted to S. marcescens exposure, and that the obligately outcrossing populations exhibited the greatest rates of adaptation. Regardless of the host population mating system, exposure to parasites did not significantly alter reproductive timing or total fecundity over the course of experimental evolution. However, both mixed mating and obligately outcrossing host populations exhibited significantly reduced mortality rates in the presence of the parasite after experimental evolution. Therefore, adaptation in both the mixed mating and obligately outcrossing populations was driven, at least in part, by the evolution of increased host defense and not changes in host life history. Thus, the host mating system altered the rate of adaptation, but not the nature of adaptive change in the host populations. PMID:28792961

The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.

2005-09-01

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein familiesmore » associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).« less

Intracellular Targeting Specificity of Novel Phthalocyanines Assessed in a Host-Parasite Model for Developing Potential Photodynamic Medicine

PubMed Central

Dutta, Sujoy; Ongarora, Benson G.; Li, Hairong; Vicente, Maria da Graca H.; Kolli, Bala K.; Chang, Kwang Poo

2011-01-01

Photodynamic therapy, unlikely to elicit drug-resistance, deserves attention as a strategy to counter this outstanding problem common to the chemotherapy of all diseases. Previously, we have broadened the applicability of this modality to photodynamic vaccination by exploiting the unusual properties of the trypanosomatid protozoa, Leishmania, i.e., their innate ability of homing to the phagolysosomes of the antigen-presenting cells and their selective photolysis therein, using transgenic mutants endogenously inducible for porphyrin accumulation. Here, we extended the utility of this host-parasite model for in vitro photodynamic therapy and vaccination by exploring exogenously supplied photosensitizers. Seventeen novel phthalocyanines (Pcs) were screened in vitro for their photolytic activity against cultured Leishmania. Pcs rendered cationic and soluble (csPcs) for cellular uptake were phototoxic to both parasite and host cells, i.e., macrophages and dendritic cells. The csPcs that targeted to mitochondria were more photolytic than those restricted to the endocytic compartments. Treatment of infected cells with endocytic csPcs resulted in their accumulation in Leishmania-containing phagolysosomes, indicative of reaching their target for photodynamic therapy, although their parasite versus host specificity is limited to a narrow range of csPc concentrations. In contrast, Leishmania pre-loaded with csPc were selectively photolyzed intracellularly, leaving host cells viable. Pre-illumination of such csPc-loaded Leishmania did not hinder their infectivity, but ensured their intracellular lysis. Ovalbumin (OVA) so delivered by photo-inactivated OVA transfectants to mouse macrophages and dendritic cells were co-presented with MHC Class I molecules by these antigen presenting cells to activate OVA epitope-specific CD8+T cells. The in vitro evidence presented here demonstrates for the first time not only the potential of endocytic csPcs for effective photodynamic therapy

First report of Orobanche ludoviciana parasitizing sunflowers

USDA-ARS?s Scientific Manuscript database

Broomrape is the common name given to a group of flowering plants belonging to the genus Orobanche that parasitize the roots of higher dicotyledonous plants. More than 100 species of Orobanche have been identified, all of which are obligate parasites that lack chlorophyll and depend upon their host ...

Advances in the application of genetic manipulation methods to apicomplexan parasites.

PubMed

Suarez, C E; Bishop, R P; Alzan, H F; Poole, W A; Cooke, B M

2017-10-01

Apicomplexan parasites such as Babesia, Theileria, Eimeria, Cryptosporidium and Toxoplasma greatly impact animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular stages. Major gaps in our understanding of the biology of these relatively poorly characterised parasites and the diseases they cause severely limit options for designing novel control methods. Here we review potentially important shared aspects of the biology of these parasites, such as cell invasion, host cell modification, and asexual and sexual reproduction, and explore the potential of the application of relatively well-established or newly emerging genetic manipulation methods, such as classical transfection or gene editing, respectively, for closing important gaps in our knowledge of the function of specific genes and proteins, and the biology of these parasites. In addition, genetic manipulation methods impact the development of novel methods of control of the diseases caused by these economically important parasites. Transient and stable transfection methods, in conjunction with whole and deep genome sequencing, were initially instrumental in improving our understanding of the molecular biology of apicomplexan parasites and paved the way for the application of the more recently developed gene editing methods. The increasingly efficient and more recently developed gene editing methods, in particular those based on the CRISPR/Cas9 system and previous conceptually similar techniques, are already contributing to additional gene function discovery using reverse genetics and related approaches. However, gene editing methods are only possible due to the increasing availability of in vitro culture, transfection, and genome sequencing and analysis techniques. We envisage that rapid progress in the development of novel gene editing techniques applied to apicomplexan parasites of

A Toxoplasma gondii protein with homology to intracellular type Na{sup +}/H{sup +} exchangers is important for osmoregulation and invasion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Francia, Maria E.; Wicher, Sarah; Pace, Douglas A.

2011-06-10

The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na{sup +}/H{sup +} exchanger in T. gondii, TgNHE3, and its co-localization withmore » the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca{sup 2+} concentration [Ca{sup 2+}]{sub i}, and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.« less

Protein moonlighting in parasitic protists.

PubMed

Ginger, Michael L

2014-12-01

Reductive evolution during the adaptation to obligate parasitism and expansions of gene families encoding virulence factors are characteristics evident to greater or lesser degrees in all parasitic protists studied to date. Large evolutionary distances separate many parasitic protists from the yeast and animal models upon which classic views of eukaryotic biochemistry are often based. Thus a combination of evolutionary divergence, niche adaptation and reductive evolution means the biochemistry of parasitic protists is often very different from their hosts and to other eukaryotes generally, making parasites intriguing subjects for those interested in the phenomenon of moonlighting proteins. In common with other organisms, the contribution of protein moonlighting to parasite biology is only just emerging, and it is not without controversy. Here, an overview of recently identified moonlighting proteins in parasitic protists is provided, together with discussion of some of the controversies.

SENSITIVITY OF THREE ENCEPHALITOZOON SPECIES TO CHLORINE AND CHLORAMINE TREATMENT AS DETECTED BY AN IN-VITRO MICROWELL PLATE ASSAY (POSTER PRESENTATION)

EPA Science Inventory

Microsporidia are obligate intracellular parasites that form environmentally resistant, infectious spores. These parasites are ubiquitous in the environment, infecting members of almost every class of verebrates and invertebrates. At least 14 microsporidian species that infect th...

Comparative Genomics Suggests that the Fungal Pathogen Pneumocystis Is an Obligate Parasite Scavenging Amino Acids from Its Host's Lungs

PubMed Central

Hauser, Philippe M.; Burdet, Frédéric X.; Cissé, Ousmane H.; Keller, Laurent; Taffé, Patrick; Sanglard, Dominique; Pagni, Marco

2010-01-01

Pneumocystis jirovecii is a fungus causing severe pneumonia in immuno-compromised patients. Progress in understanding its pathogenicity and epidemiology has been hampered by the lack of a long-term in vitro culture method. Obligate parasitism of this pathogen has been suggested on the basis of various features but remains controversial. We analysed the 7.0 Mb draft genome sequence of the closely related species Pneumocystis carinii infecting rats, which is a well established experimental model of the disease. We predicted 8’085 (redundant) peptides and 14.9% of them were mapped onto the KEGG biochemical pathways. The proteome of the closely related yeast Schizosaccharomyces pombe was used as a control for the annotation procedure (4’974 genes, 14.1% mapped). About two thirds of the mapped peptides of each organism (65.7% and 73.2%, respectively) corresponded to crucial enzymes for the basal metabolism and standard cellular processes. However, the proportion of P. carinii genes relative to those of S. pombe was significantly smaller for the “amino acid metabolism” category of pathways than for all other categories taken together (40 versus 114 against 278 versus 427, P<0.002). Importantly, we identified in P. carinii only 2 enzymes specifically dedicated to the synthesis of the 20 standard amino acids. By contrast all the 54 enzymes dedicated to this synthesis reported in the KEGG atlas for S. pombe were detected upon reannotation of S. pombe proteome (2 versus 54 against 278 versus 427, P<0.0001). This finding strongly suggests that species of the genus Pneumocystis are scavenging amino acids from their host's lung environment. Consequently, they would have no form able to live independently from another organism, and these parasites would be obligate in addition to being opportunistic. These findings have implications for the management of patients susceptible to P. jirovecii infection given that the only source of infection would be other humans. PMID

One Health: parasites and beyond.

PubMed

Blake, Damer P; Betson, Martha

2017-01-01

The field of parasitism is broad, encompassing relationships between organisms where one benefits at the expense of another. Traditionally the discipline focuses on eukaryotes, with the study of bacteria and viruses complementary but distinct. Nonetheless, parasites vary in size and complexity from single celled protozoa, to enormous plants like those in the genus Rafflesia. Lifecycles range from obligate intracellular to extensive exoparasitism. Examples of parasites include high-profile medical and zoonotic pathogens such as Plasmodium, veterinary pathogens of wild and captive animals and many of the agents which cause neglected tropical diseases, stretching to parasites which infect plants and other parasites (e.g. Kikuchi et al. 2011; Hotez et al. 2014; Blake et al. 2015; Hemingway, 2015; Meekums et al. 2015; Sandlund et al. 2015). The breadth of parasitology has been matched by the variety of ways in which parasites are studied, drawing upon biological, chemical, molecular, epidemiological and other expertise. Despite such breadth bridging between disciplines has commonly been problematic, regardless of extensive encouragement from government agencies, peer audiences and funding bodies promoting multidisciplinary research. Now, progress in understanding and collaboration can benefit from establishment of the One Health concept (Zinsstag et al. 2012; Stark et al. 2015). One Health draws upon biological, environmental, medical, veterinary and social science disciplines in order to improve human, animal and environmental health, although it remains tantalizingly difficult to engage many relevant parties. For infectious diseases traditional divides have been exacerbated as the importance of wildlife reservoirs, climate change, food production systems and socio-economic diversity have been recognized but often not addressed in a multidisciplinary manner. In response the 2015 Autumn Symposium organized by the British Society for Parasitology (BSP; https

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

PubMed Central

Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

2014-01-01

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation.

PubMed

Marsolier, J; Perichon, M; DeBarry, J D; Villoutreix, B O; Chluba, J; Lopez, T; Garrido, C; Zhou, X Z; Lu, K P; Fritsch, L; Ait-Si-Ali, S; Mhadhbi, M; Medjkane, S; Weitzman, J B

2015-04-16

Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PIN1 in T. annulata (TaPIN1) that is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPIN1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7, leading to its degradation and subsequent stabilization of c-JUN, which promotes transformation. We performed in vitro and in silico analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPIN1 is directly inhibited by the anti-parasite drug buparvaquone (and other known PIN1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerization is thus a conserved mechanism that is important in cancer and is used by Theileria parasites to manipulate host oncogenic signalling.

Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation

PubMed Central

Marsolier, J.; Perichon, M.; DeBarry, JD.; Villoutreix, BO.; Chluba, J.; Lopez, T.; Garrido, C.; Zhou, XZ.; Lu, KP.; Fritsch, L.; Ait-Si-Ali, S.; Mhadhbi, M; Medjkane, S.; Weitzman, JB.

2014-01-01

Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack the genetic and epigenetic machinery to change phenotypic states. Amongst the Apicomplexa phylum of obligate intracellular parasites which cause veterinary and human diseases, Theileria is the only genus which transforms its mammalian host cells1. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-12. The transformed phenotypes are reversed by treatment with the theilericidal drug Buparvaquone3. We used comparative genomics to identify a homologue of the Peptidyl Prolyl Isomerase Pin1 (designated TaPin1) in T. annulata which is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPin1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7 leading to its degradation and subsequent stabilization of c-Jun which promotes transformation. We performed in vitro analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPin1 is directly inhibited by the anti-parasite drug Buparvaquone (and other known Pin1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerisation is thus a conserved mechanism which is important in cancer and is used by Theileria parasites to manipulate host oncogenic signaling. PMID:25624101

Biological control potential of the obligate parasite Pasteuria penetransagainst the root-knot nematode, Meloidogyne incognita infestation in Brinjal.

PubMed

Kumari, N Swarna; Sivakumar, C V

2005-01-01

The efficacy of the obligate bacterial parasite, Pasteuria penetrans against the rootknot nematode, Meloidogyne incognita infestation was assessed in brinjal. The seedling pans with sterilized soil were inoculated with nematodes and root powder of P. penetrans were applied at different dosages viz., 0 x 10(6), 0.5 x 10(6) spores and 1 x 10(6) spores/pan. Seeds of brinjal cv Co2 were sown in the pans and seedlings were allowed to grow. The seedlings were transplanted to microplots containing sterilized soil. Observations on nematode infestation and plant growth were recorded at seedling, flowering, and fruiting stages. Nematode infestation was significantly reduced by P. penetrans treatment. There was 22, 75 and 86% reduction in nematode population of soil over control at seedling, flowering and fruiting stages, respectively, at higher spore density (1 x 10(6)). Egg mass production was decreased by 63, 78 and 89% over control at 35 (seedling), 100 (flowering) and 160 (fruiting) days after sowing respectively, at 1 x 10(6) spores treated soil. The parasitizing ability of P. penetrans increased with the age of the crop. At higher spore density the percentage of parasitization was increased from 52.0 (35 days after sowing) to 90.0 (160 days after sowing) %. At these stages of the crop, the spore load per juvenile also increased at the higher dose. The P. penetrans application enhanced the plant growth. The weight of the shoot was increased by 17.6% whereas root weight by 41.0% over the control at fruiting stage. The experimental results revealed the potential use of P. penetrans as biological control agent of M. incognita. Application of P. penetrans spores in the nursery is a good strategy since the mass multiplication is quite difficult.

Plants that attack plants: molecular elucidation of plant parasitism.

PubMed

Yoshida, Satoko; Shirasu, Ken

2012-12-01

Obligate parasitic plants in the family Orobanchaceae, such as Striga and Orobanche (including Phelipanche) spp., parasitize important crops and cause severe agricultural damage. Recent molecular studies have begun to reveal how these parasites have adapted to hosts in a parasitic lifecycle. The parasites detect nearby host roots and germinate by a mechanism that seems to have evolved from a conserved germination system found in non-parasites. The development of a specialized infecting organ called a haustorium is a unique feature of plant parasites and is triggered by host compounds and redox signals. Newly developed genomic and genetic resources will facilitate more rapid progress toward a molecular understanding of plant parasitism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of H(+)-pyrophosphatase activity in the regulation of intracellular pH in a scuticociliate parasite of turbot: Physiological effects.

PubMed

Mallo, Natalia; Lamas, Jesús; de Felipe, Ana-Paula; Sueiro, Rosa-Ana; Fontenla, Francisco; Leiro, José-Manuel

2016-10-01

The scuticociliatosis is a very serious disease that affects the cultured turbot, and whose causal agent is the anphizoic and marine euryhaline ciliate Philasterides dicentrarchi. Several protozoans possess acidic organelles that contain high concentrations of pyrophosphate (PPi), Ca(2+) and other elements with essential roles in vesicular trafficking, pH homeostasis and osmoregulation. P. dicentrarchi possesses a pyrophosphatase (H(+)-PPase) that pumps H(+) through the membranes of vacuolar and alveolar sacs. These compartments share common features with the acidocalcisomes described in other parasitic protozoa (e.g. acid content and Ca(2+) storage). We evaluated the effects of Ca(2+) and ATP on H (+)-PPase activity in this ciliate and analyzed their role in maintaining intracellular pH homeostasis and osmoregulation, by the addition of PPi and inorganic molecules that affect osmolarity. Addition of PPi led to acidification of the intracellular compartments, while the addition of ATP, CaCl2 and bisphosphonates analogous of PPi and Ca(2+) metabolism regulators led to alkalinization and a decrease in H(+)-PPase expression in trophozoites. Addition of NaCl led to proton release, intracellular Ca(2+) accumulation and downregulation of H(+)-PPase expression. We conclude that the regulation of the acidification of intracellular compartments may be essential for maintaining the intracellular pH homeostasis necessary for survival of ciliates and their adaptation to salt stress, which they will presumably face during the endoparasitic phase, in which the salinity levels are lower than in their natural environment. Copyright © 2016 Elsevier Inc. All rights reserved.

Phylogenetic Diversity of NTT Nucleotide Transport Proteins in Free-Living and Parasitic Bacteria and Eukaryotes

PubMed Central

Major, Peter; Embley, T. Martin

2017-01-01

Plasma membrane-located nucleotide transport proteins (NTTs) underpin the lifestyle of important obligate intracellular bacterial and eukaryotic pathogens by importing energy and nucleotides from infected host cells that the pathogens can no longer make for themselves. As such their presence is often seen as a hallmark of an intracellular lifestyle associated with reductive genome evolution and loss of primary biosynthetic pathways. Here, we investigate the phylogenetic distribution of NTT sequences across the domains of cellular life. Our analysis reveals an unexpectedly broad distribution of NTT genes in both host-associated and free-living prokaryotes and eukaryotes. We also identify cases of within-bacteria and bacteria-to-eukaryote horizontal NTT transfer, including into the base of the oomycetes, a major clade of parasitic eukaryotes. In addition to identifying sequences that retain the canonical NTT structure, we detected NTT gene fusions with HEAT-repeat and cyclic nucleotide binding domains in Cyanobacteria, pathogenic Chlamydiae and Oomycetes. Our results suggest that NTTs are versatile functional modules with a much wider distribution and a broader range of potential roles than has previously been appreciated. PMID:28164241

Keeping eggs warm: thermal and developmental advantages for parasitic cuckoos of laying unusually thick-shelled eggs

NASA Astrophysics Data System (ADS)

Yang, Canchao; Huang, Qiuli; Wang, Longwu; Du, Wei-Guo; Liang, Wei; Møller, Anders Pape

2018-02-01

Obligate brood parasites have evolved unusually thick-shelled eggs, which are hypothesized to possess a variety of functions such as resistance to puncture ejection by their hosts. In this study, we tested the hypothesis that obligate brood parasites lay unusually thick-shelled eggs to retain more heat for the developing embryo and thus contribute to early hatching of parasite eggs. By doing so, we used an infrared thermal imaging system as a non-invasive method to quantify the temperature of eggshells of common cuckoos ( Cuculus canorus) and their Oriental reed warbler ( Acrocephalus orientalis) hosts in an experiment that artificially altered the duration of incubation. Our results showed that cuckoo eggshells had higher temperature than host eggs during incubation, but also less fluctuations in temperature during incubation disturbance. Therefore, there was a thermal and hence a developmental advantage for brood parasitic cuckoos of laying thick-shelled eggs, providing another possible explanation for the unusually thick-shelled eggs of obligate brood parasites and earlier hatching of cuckoo eggs compared to those of the host.

Keeping eggs warm: thermal and developmental advantages for parasitic cuckoos of laying unusually thick-shelled eggs.

PubMed

Yang, Canchao; Huang, Qiuli; Wang, Longwu; Du, Wei-Guo; Liang, Wei; Møller, Anders Pape

2018-01-02

Obligate brood parasites have evolved unusually thick-shelled eggs, which are hypothesized to possess a variety of functions such as resistance to puncture ejection by their hosts. In this study, we tested the hypothesis that obligate brood parasites lay unusually thick-shelled eggs to retain more heat for the developing embryo and thus contribute to early hatching of parasite eggs. By doing so, we used an infrared thermal imaging system as a non-invasive method to quantify the temperature of eggshells of common cuckoos (Cuculus canorus) and their Oriental reed warbler (Acrocephalus orientalis) hosts in an experiment that artificially altered the duration of incubation. Our results showed that cuckoo eggshells had higher temperature than host eggs during incubation, but also less fluctuations in temperature during incubation disturbance. Therefore, there was a thermal and hence a developmental advantage for brood parasitic cuckoos of laying thick-shelled eggs, providing another possible explanation for the unusually thick-shelled eggs of obligate brood parasites and earlier hatching of cuckoo eggs compared to those of the host.

The Genome of the Obligately Intracellular Bacterium Ehrlichia canis Reveals Themes of Complex Membrane Structure and Immune Evasion Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mavromatis, K; Doyle, C Kuyler; Lykidis, A

2006-01-01

Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, {alpha}-proteobacterium, is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, 17 putative pseudogenes, and a substantial proportion of noncoding sequence (27%). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences and a unique serine-threonine bias associated with the potential for O glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associatedmore » with immune evasion were identified, one of which contains poly(G-C) tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Genes associated with pathogen-host interactions were identified, including a small group encoding proteins (n = 12) with tandem repeats and another group encoding proteins with eukaryote-like ankyrin domains (n = 7).« less

Bridging the Gulf: Phytophthora and Downy Mildews Are Connected by Rare Grass Parasites

PubMed Central

Thines, Marco

2009-01-01

Downy mildews and root and foliar rots caused by Phytophthora are among the most destructive plant pathogens and therefore have attracted considerable attention during the past two decades. Although it has been realized that a close phylogenetic relationship exists, so far sharp distinction has been made between the obligate biotrophic downy mildews and the hemibiotrophic Phytophthora. In the study presented here, it is shown that a continuum of character states from hemibiotrophic Phytophthora species to obligate biotrophic downy mildews is present. Intermediate character states between downy mildews and Phytophthora species exist in several rare parasites of grasses, which are not embedded within the major clades of the downy mildews but are placed sister to these, with unresolved affinities to both these clades and to Phytophthora. They still have retained traits hitherto thought to be exclusive for Phytophthora. A careful review of previous research is presented and it is highlighted that uniquely for downy mildews, Poakatesthia may form an intracellular mycelium, growing through several host cells. In addition, scanning electron microscopy reveals that sporangiophore growth is not determinate in Viennotia and that outgrowth from sporangiophores is very similar to Phytophthora infestans. It is concluded that the sharp morphological distinction between downy mildews and Phytophthora species (that are often placed in separate families and even different orders), is rather artificial, since all features thought to be exclusive to Phytophthora or the downy mildews are united in the rare grass-parasitizing down mildew genera Viennotia and Poakatesthia and the enigmatic genus Sclerophthora. Therefore, several paradigms regarding the distinction between Phytophthora and the downy mildews need to be reconsidered. PMID:19274081

Bridging the gulf: Phytophthora and downy mildews are connected by rare grass parasites.

PubMed

Thines, Marco

2009-01-01

Downy mildews and root and foliar rots caused by Phytophthora are among the most destructive plant pathogens and therefore have attracted considerable attention during the past two decades. Although it has been realized that a close phylogenetic relationship exists, so far sharp distinction has been made between the obligate biotrophic downy mildews and the hemibiotrophic Phytophthora. In the study presented here, it is shown that a continuum of character states from hemibiotrophic Phytophthora species to obligate biotrophic downy mildews is present. Intermediate character states between downy mildews and Phytophthora species exist in several rare parasites of grasses, which are not embedded within the major clades of the downy mildews but are placed sister to these, with unresolved affinities to both these clades and to Phytophthora. They still have retained traits hitherto thought to be exclusive for Phytophthora. A careful review of previous research is presented and it is highlighted that uniquely for downy mildews, Poakatesthia may form an intracellular mycelium, growing through several host cells. In addition, scanning electron microscopy reveals that sporangiophore growth is not determinate in Viennotia and that outgrowth from sporangiophores is very similar to Phytophthora infestans. It is concluded that the sharp morphological distinction between downy mildews and Phytophthora species (that are often placed in separate families and even different orders), is rather artificial, since all features thought to be exclusive to Phytophthora or the downy mildews are united in the rare grass-parasitizing down mildew genera Viennotia and Poakatesthia and the enigmatic genus Sclerophthora. Therefore, several paradigms regarding the distinction between Phytophthora and the downy mildews need to be reconsidered.

In Silico Ionomics Segregates Parasitic from Free-Living Eukaryotes

PubMed Central

Greganova, Eva; Steinmann, Michael; Mäser, Pascal; Fankhauser, Niklaus

2013-01-01

Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals. PMID:24048281

In silico ionomics segregates parasitic from free-living eukaryotes.

PubMed

Greganova, Eva; Steinmann, Michael; Mäser, Pascal; Fankhauser, Niklaus

2013-01-01

Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals.

Evolutionary Origins of Rhizarian Parasites.

PubMed

Sierra, Roberto; Cañas-Duarte, Silvia J; Burki, Fabien; Schwelm, Arne; Fogelqvist, Johan; Dixelius, Christina; González-García, Laura N; Gile, Gillian H; Slamovits, Claudio H; Klopp, Christophe; Restrepo, Silvia; Arzul, Isabelle; Pawlowski, Jan

2016-04-01

The SAR group (Stramenopila, Alveolata, Rhizaria) is one of the largest clades in the tree of eukaryotes and includes a great number of parasitic lineages. Rhizarian parasites are obligate and have devastating effects on commercially important plants and animals but despite this fact, our knowledge of their biology and evolution is limited. Here, we present rhizarian transcriptomes from all major parasitic lineages in order to elucidate their evolutionary relationships using a phylogenomic approach. Our results suggest that Ascetosporea, parasites of marine invertebrates, are sister to the novel clade Apofilosa. The phytomyxean plant parasites branch sister to the vampyrellid algal ectoparasites in the novel clade Phytorhiza. They also show that Ascetosporea + Apofilosa + Retaria + Filosa + Phytorhiza form a monophyletic clade, although the branching pattern within this clade is difficult to resolve and appears to be model-dependent. Our study does not support the monophyly of the rhizarian parasitic lineages (Endomyxa), suggesting independent origins for rhizarian animal and plant parasites. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dynamics of the antibody-T.cruzi competition during Chagas infection: Prognostic relevance of intracellular replication

NASA Astrophysics Data System (ADS)

Sibona, G. J.; Condat, C. A.; Isasi, S. Cossy

2005-02-01

A recently proposed model for the competitive parasite-antibody interactions in Chagas disease is extended by separately describing the parasitic intracellular and extracellular phases. The model solutions faithfully reproduce available population data and yield predictions for parasite-induced cardiac cell damage.

Genetic diversity, virulence and fitness evolution in an obligate fungal parasite of bees.

PubMed

Evison, S E F; Foley, K; Jensen, A B; Hughes, W O H

2015-01-01

Within-host competition is predicted to drive the evolution of virulence in parasites, but the precise outcomes of such interactions are often unpredictable due to many factors including the biology of the host and the parasite, stochastic events and co-evolutionary interactions. Here, we use a serial passage experiment (SPE) with three strains of a heterothallic fungal parasite (Ascosphaera apis) of the Honey bee (Apis mellifera) to assess how evolving under increasing competitive pressure affects parasite virulence and fitness evolution. The results show an increase in virulence after successive generations of selection and consequently faster production of spores. This faster sporulation, however, did not translate into more spores being produced during this longer window of sporulation; rather, it appeared to induce a loss of fitness in terms of total spore production. There was no evidence to suggest that a greater diversity of competing strains was a driver of this increased virulence and subsequent fitness cost, but rather that strain-specific competitive interactions influenced the evolutionary outcomes of mixed infections. It is possible that the parasite may have evolved to avoid competition with multiple strains because of its heterothallic mode of reproduction, which highlights the importance of understanding parasite biology when predicting disease dynamics. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Wholly Rickettsia! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells.

PubMed

Driscoll, Timothy P; Verhoeve, Victoria I; Guillotte, Mark L; Lehman, Stephanie S; Rennoll, Sherri A; Beier-Sexton, Magda; Rahman, M Sayeedur; Azad, Abdu F; Gillespie, Joseph J

2017-09-26

Reductive genome evolution has purged many metabolic pathways from obligate intracellular Rickettsia ( Alphaproteobacteria ; Rickettsiaceae ). While some aspects of host-dependent rickettsial metabolism have been characterized, the array of host-acquired metabolites and their cognate transporters remains unknown. This dearth of information has thwarted efforts to obtain an axenic Rickettsia culture, a major impediment to conventional genetic approaches. Using phylogenomics and computational pathway analysis, we reconstructed the Rickettsia metabolic and transport network, identifying 51 host-acquired metabolites (only 21 previously characterized) needed to compensate for degraded biosynthesis pathways. In the absence of glycolysis and the pentose phosphate pathway, cell envelope glycoconjugates are synthesized from three imported host sugars, with a range of additional host-acquired metabolites fueling the tricarboxylic acid cycle. Fatty acid and glycerophospholipid pathways also initiate from host precursors, and import of both isoprenes and terpenoids is required for the synthesis of ubiquinone and the lipid carrier of lipid I and O-antigen. Unlike metabolite-provisioning bacterial symbionts of arthropods, rickettsiae cannot synthesize B vitamins or most other cofactors, accentuating their parasitic nature. Six biosynthesis pathways contain holes (missing enzymes); similar patterns in taxonomically diverse bacteria suggest alternative enzymes that await discovery. A paucity of characterized and predicted transporters emphasizes the knowledge gap concerning how rickettsiae import host metabolites, some of which are large and not known to be transported by bacteria. Collectively, our reconstructed metabolic network offers clues to how rickettsiae hijack host metabolic pathways. This blueprint for growth determinants is an important step toward the design of axenic media to rescue rickettsiae from the eukaryotic cell. IMPORTANCE A hallmark of obligate intracellular

Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

PubMed

Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

2014-09-01

Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

Heightened exposure to parasites favors the evolution of immunity in brood parasitic cowbirds

USGS Publications Warehouse

Hahn, Caldwell; Reisen, William K.

2011-01-01

Immunologists and evolutionary biologists are interested in how the immune system evolves to fit an ecological niche. We studied the relationship between exposure to parasites and strength of immunity by investigating the response of two species of New World cowbirds (genus Molothrus, Icteridae), obligate brood parasites with contrasting life history strategies, to experimental arboviral infection. The South American shiny cowbird (M. bonariensis) is an extreme host-generalist that lays its eggs in the nests of >225 different avian species. The Central American bronzed cowbird (M. aeneus) is a relative host-specialist that lays its eggs preferentially in the nests of approximately 12 orioles in a single sister genus. West Nile virus provided a strong challenge and delineated immune differences between these species. The extreme host-generalist shiny cowbird, like the North American host-generalist, the brown-headed cowbird, showed significantly lower viremia to three arboviruses than related icterid species that were not brood parasites. The bronzed cowbird showed intermediate viremia. These findings support the interpretation that repeated exposure to a high diversity of parasites favors the evolution of enhanced immunity in brood parasitic cowbirds and makes them useful models for future studies of innate immunity.

MEASURE OCCURRENCE AND EXPOSURE TO CCL-RELATED, EMERGING AND REGULATED WATERBORNE HUMAN PROTOZOA

EPA Science Inventory

Pathogenic waterborne protozoa (Giardia, Cryptosporidium) have been identified as significant etiological agents in the transmission of waterborne disease. Microsporidians, which are on the Agency's Contaminant Candidate List, are obligate intracellular parasites of invertebrate...

Function of Macrophage and Parasite Phosphatases in Leishmaniasis

PubMed Central

Soulat, Didier; Bogdan, Christian

2017-01-01

The kinetoplastid protozoan parasites belonging to the genus Leishmania are the causative agents of different clinical forms of leishmaniasis, a vector-borne infectious disease with worldwide prevalence. The protective host immune response against Leishmania parasites relies on myeloid cells such as dendritic cells and macrophages in which upon stimulation by cytokines (e.g., interferon-γ) a complex network of signaling pathways is switched on leading to strong antimicrobial activities directed against the intracellular parasite stage. The regulation of these pathways classically depends on post-translational modifications of proteins, with phosphorylation events playing a cardinal role. Leishmania parasites deactivate their phagocytic host cells by inducing specific mammalian phosphatases that are capable to impede signaling. On the other hand, there is now also evidence that Leishmania spp. themselves express phosphatases that might target host cell molecules and thereby facilitate the intracellular survival of the parasite. This review will present an overview on the modulation of host phosphatases by Leishmania parasites as well as on the known families of Leishmania phosphatases and their possible function as virulence factors. A more detailed understanding of the role of phosphatases in Leishmania–host cell interactions might open new avenues for the treatment of non-healing, progressive forms of leishmaniasis. PMID:29312331

Success of cuckoo catfish brood parasitism reflects coevolutionary history and individual experience of their cichlid hosts

PubMed Central

Polačik, Matej; Smith, Carl; Honza, Marcel; Reichard, Martin

2018-01-01

Obligate brood parasites manipulate other species into raising their offspring. Avian and insect brood parasitic systems demonstrate how interacting species engage in reciprocal coevolutionary arms races through behavioral and morphological adaptations and counteradaptations. Mouthbrooding cichlid fishes are renowned for their remarkable evolutionary radiations and complex behaviors. In Lake Tanganyika, mouthbrooding cichlids are exploited by the only obligate nonavian vertebrate brood parasite, the cuckoo catfish Synodontis multipunctatus. We show that coevolutionary history and individual learning both have a major impact on the success of cuckoo catfish parasitism between coevolved sympatric and evolutionarily naïve allopatric cichlid species. The rate of cuckoo catfish parasitism in coevolved Tanganyikan hosts was 3 to 11 times lower than in evolutionarily naïve cichlids. Moreover, using experimental infections, we demonstrate that parasite egg rejection in sympatric hosts was much higher, leading to seven times greater parasite survival in evolutionarily naïve than sympatric hosts. However, a high rejection frequency of parasitic catfish eggs by coevolved sympatric hosts came at a cost of increased rejection of their own eggs. A significant cost of catfish parasitism was universal, except for coevolved sympatric cichlid species with previous experience of catfish parasitism, demonstrating that learning and individual experience both contribute to a successful host response. PMID:29732407

Discovery and Complete Genome Sequence of a Bacteriophage from an Obligate Intracellular Symbiont of a Cellulolytic Protist in the Termite Gut

PubMed Central

Pramono, Ajeng K.; Kuwahara, Hirokazu; Itoh, Takehiko; Toyoda, Atsushi; Yamada, Akinori; Hongoh, Yuichi

2017-01-01

Termites depend nutritionally on their gut microbes, and protistan, bacterial, and archaeal gut communities have been extensively studied. However, limited information is available on viruses in the termite gut. We herein report the complete genome sequence (99,517 bp) of a phage obtained during a genome analysis of “Candidatus Azobacteroides pseudotrichonymphae” phylotype ProJPt-1, which is an obligate intracellular symbiont of the cellulolytic protist Pseudotrichonympha sp. in the gut of the termite Prorhinotermes japonicus. The genome of the phage, designated ProJPt-Bp1, was circular or circularly permuted, and was not integrated into the two circular chromosomes or five circular plasmids composing the host ProJPt-1 genome. The phage was putatively affiliated with the order Caudovirales based on sequence similarities with several phage-related genes; however, most of the 52 protein-coding sequences had no significant homology to sequences in the databases. The phage genome contained a tRNA-Gln (CAG) gene, which showed the highest sequence similarity to the tRNA-Gln (CAA) gene of the host “Ca. A. pseudotrichonymphae” phylotype ProJPt-1. Since the host genome lacked a tRNA-Gln (CAG) gene, the phage tRNA gene may compensate for differences in codon usage bias between the phage and host genomes. The phage genome also contained a non-coding region with high nucleotide sequence similarity to a region in one of the host plasmids. No other phage-related sequences were found in the host ProJPt-1 genome. To the best of our knowledge, this is the first report of a phage from an obligate, mutualistic endosymbiont permanently associated with eukaryotic cells. PMID:28321010

Impairment of T Cell Function in Parasitic Infections

PubMed Central

Rodrigues, Vasco; Cordeiro-da-Silva, Anabela; Laforge, Mireille; Ouaissi, Ali; Akharid, Khadija; Silvestre, Ricardo; Estaquier, Jérôme

2014-01-01

In mammals subverted as hosts by protozoan parasites, the latter and/or the agonists they release are detected and processed by sensors displayed by many distinct immune cell lineages, in a tissue(s)-dependent context. Focusing on the T lymphocyte lineage, we review our present understanding on its transient or durable functional impairment over the course of the developmental program of the intracellular parasites Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Trypanosoma cruzi in their mammalian hosts. Strategies employed by protozoa to down-regulate T lymphocyte function may act at the initial moment of naïve T cell priming, rendering T cells anergic or unresponsive throughout infection, or later, exhausting T cells due to antigen persistence. Furthermore, by exploiting host feedback mechanisms aimed at maintaining immune homeostasis, parasites can enhance T cell apoptosis. We will discuss how infections with prominent intracellular protozoan parasites lead to a general down-regulation of T cell function through T cell anergy and exhaustion, accompanied by apoptosis, and ultimately allowing pathogen persistence. PMID:24551250

Competition promotes the evolution of host generalists in obligate parasites

PubMed Central

Johnson, Kevin P.; Malenke, Jael R.; Clayton, Dale H.

2009-01-01

Ecological theory traditionally predicts that interspecific competition selects for an increase in ecological specialization. Specialization, in turn, is often thought to be an evolutionary ‘dead end,’ with specialist lineages unlikely to evolve into generalist lineages. In host–parasite systems, this specialization can take the form of host specificity, with more specialized parasites using fewer hosts. We tested the hypothesis that specialists are evolutionarily more derived, and whether competition favours specialization, using the ectoparasitic feather lice of doves. Phylogenetic analyses revealed that complete host specificity is actually the ancestral condition, with generalists repeatedly evolving from specialist ancestors. These multiple origins of generalists are correlated with the presence of potentially competing species of the same genus. A competition experiment with captive doves and lice confirmed that congeneric species of lice do, in fact, have the potential to compete in ecological time. Taken together, these results suggest that interspecific competition can favour the evolution of host generalists, not specialists, over macroevolutionary time. PMID:19710056

Monoclonal Antibodies to Intracellular Stages of Cryptosporidium parvum Define Life Cycle Progression In Vitro.

PubMed

Wilke, Georgia; Ravindran, Soumya; Funkhouser-Jones, Lisa; Barks, Jennifer; Wang, Qiuling; VanDussen, Kelli L; Stappenbeck, Thaddeus S; Kuhlenschmidt, Theresa B; Kuhlenschmidt, Mark S; Sibley, L David

2018-06-27

Among the obstacles hindering Cryptosporidium research is the lack of an in vitro culture system that supports complete life development and propagation. This major barrier has led to a shortage of widely available anti- Cryptosporidium antibodies and a lack of markers for staging developmental progression. Previously developed antibodies against Cryptosporidium were raised against extracellular stages or recombinant proteins, leading to antibodies with limited reactivity across the parasite life cycle. Here we sought to create antibodies that recognize novel epitopes that could be used to define intracellular development. We identified a mouse epithelial cell line that supported C. parvum growth, enabling immunization of mice with infected cells to create a bank of monoclonal antibodies (MAbs) against intracellular parasite stages while avoiding the development of host-specific antibodies. From this bank, we identified 12 antibodies with a range of reactivities across the parasite life cycle. Importantly, we identified specific MAbs that can distinguish different life cycle stages, such as trophozoites, merozoites, type I versus II meronts, and macrogamonts. These MAbs provide valuable tools for the Cryptosporidium research community and will facilitate future investigation into parasite biology. IMPORTANCE Cryptosporidium is a protozoan parasite that causes gastrointestinal disease in humans and animals. Currently, there is a limited array of antibodies available against the parasite, which hinders imaging studies and makes it difficult to visualize the parasite life cycle in different culture systems. In order to alleviate this reagent gap, we created a library of novel antibodies against the intracellular life cycle stages of Cryptosporidium We identified antibodies that recognize specific life cycle stages in distinctive ways, enabling unambiguous description of the parasite life cycle. These MAbs will aid future investigation into Cryptosporidium biology and

Grand-scale theft: kleptoplasty in parasitic plants?

PubMed

Krause, Kirsten

2015-04-01

The angiosperm Rafflesia lives as an obligate holoparasite in intimate contact with its hosts, vines in the genus Tetrastigma. The hosts are forced to supply the parasite with all the necessary nutrients. Novel data tentatively suggest that the thievery may happen on a larger scale and include entire organellar genomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular characterization of Enterocytozoon bieneusi in wild carnivores in Spain

USDA-ARS?s Scientific Manuscript database

Microsporidia comprises a diverse group of obligate intracellular parasites that infect all major animal groups from invertebrates to fish to birds and mammals, including domesticated animals and humans. Among Microsporidia, Enterocytozoon bieneusi is the most frequently detected species in humans a...

Molecular characterization of Enterocytozoon bieneusi in wild carnivores in Spain

USDA-ARS?s Scientific Manuscript database

Microsporidia comprises a diverse group of obligate intracellular parasites that infect a broad range of invertebrates and vertebrates. Among Microsporidia, Enterocytozoon bieneusi is the most frequently detected species in humans and animals worldwide bringing into question the possible role of ani...

In-vitro Cell Culture and Real-time Reverse Transcriptase PCR-based Assays to Detect Infective Toxoplas gondii Oocysts

EPA Science Inventory

Toxoplasma gondii is an obligate intracellular, apicomplexan parasite that infects humans. It is ubiquitous in nature and seroprevalence in the United States and in Europe ranges from 25->70%. Although typically associated with causing foodborne outbreaks, recent studies in Canad...

Reduction of Toxoplasma gondii Development Due to Inhibition of Parasite Antioxidant Enzymes by a Dinuclear Iron(III) Compound

PubMed Central

Portes, J. A.; Souza, T. G.; dos Santos, T. A. T.; da Silva, L. L. R.; Ribeiro, T. P.; Pereira, M. D.; Horn, A.; Fernandes, C.; DaMatta, R. A.; de Souza, W.

2015-01-01

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan that can infect a wide range of vertebrate cells. Here, we describe the cytotoxic effects of the dinuclear iron compound [Fe(HPCINOL)(SO4)]2-μ-oxo, in which HPCINOL is the ligand 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, on T. gondii infecting LLC-MK2 host cells. This compound was not toxic to LLC-MK2 cells at concentrations of up to 200 μM but was very active against the parasite, with a 50% inhibitory concentration (IC50) of 3.6 μM after 48 h of treatment. Cyst formation was observed after treatment, as indicated by the appearance of a cyst wall, Dolichos biflorus lectin staining, and scanning and transmission electron microscopy characteristics. Ultrastructural changes were also seen in T. gondii, including membrane blebs and clefts in the cytoplasm, with inclusions similar to amylopectin granules, which are typically found in bradyzoites. An analysis of the cell death pathways in the parasite revealed that the compound caused a combination of apoptosis and autophagy. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction in superoxide dismutase and catalase activities in the treated parasites and the presence of reactive oxygen species within the parasitophorous vacuoles were observed, indicating an impaired protozoan response against these radicals. These findings suggest that this compound disturbs the redox equilibrium of T. gondii, inducing cystogenesis and parasite death. PMID:26392498

Anti-Plasmodial Activity of Aroylhydrazone and Thiosemicarbazone Iron Chelators: Effect on Erythrocyte Membrane Integrity, Parasite Development and the Intracellular Labile Iron Pool

PubMed Central

Walcourt, Asikiya; Kurantsin-Mills, Joseph; Kwagyan, John; Adenuga, Babafemi B.; Kalinowski, Danuta S.; Lovejoy, David B.; Lane, Darius J. R.; Richardson, Des R.

2013-01-01

Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50 = 4.45 ± 1.70, 10.30 ± 4.40, and 3.64 ± 2.00 μM, respectively) than DFO (IC50 = 23.43 ± 3.40 μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activity, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization. PMID:24028863

Eimeria-induced chicken cNK-2 is an anti-infective host defense peptide and an immunomodulator of host innate immunity

USDA-ARS?s Scientific Manuscript database

Avian coccidiosis is one of the most widespread infectious diseases of chickens. The etiologic agent of avian coccidiosis is Eimeria, a genus of eukaryotic obligate intracellular parasites belonging to the phylum Apicomplexa. Clinical manifestations of infection include damage to the intestinal epit...

Microsporidia

USDA-ARS?s Scientific Manuscript database

Microsporidia are unicellular obligate intracellular spore forming eukaryotes classified among the protists. As parasites, they have been reported from every major group of animals from other protists to mammals and man. They are economically and medically important and can be found environmentally ...

Serological Evidence of Toxoplasma gondii infection in five species of bats in China

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii is an obligate intracellular protozoan parasite which can infect almost all warm-blooded animals and humans with a worldwide distribution. Bats are reservoirs for an increasing number of emerging zoonotic viruses, such as henipaviruses and severe acute respiratory syndrome (SARS) c...

SNSAG5 IS AN ALTERNATIVE SURFACE ANTIGEN OF SARCOCYSTIS NEURONA STRAINS THAT IS MUTUALLY EXCLUSIVE TO SNSAG1

USDA-ARS?s Scientific Manuscript database

Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). Previous work has identified a gene family of paralogous surface antigens in S. neurona called SnSAGs. These surface proteins are immunogenic in their host animals, and are therefore can...

Host nutrition alters the variance in parasite transmission potential

PubMed Central

Vale, Pedro F.; Choisy, Marc; Little, Tom J.

2013-01-01

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts. PMID:23407498

Host nutrition alters the variance in parasite transmission potential.

PubMed

Vale, Pedro F; Choisy, Marc; Little, Tom J

2013-04-23

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts.

De novo assembly and characterization of the transcriptome of the parasitic weed dodder identifies genes associated with plant parasitism.

PubMed

Ranjan, Aashish; Ichihashi, Yasunori; Farhi, Moran; Zumstein, Kristina; Townsley, Brad; David-Schwartz, Rakefet; Sinha, Neelima R

2014-11-01

Parasitic flowering plants are one of the most destructive agricultural pests and have major impact on crop yields throughout the world. Being dependent on finding a host plant for growth, parasitic plants penetrate their host using specialized organs called haustoria. Haustoria establish vascular connections with the host, which enable the parasite to steal nutrients and water. The underlying molecular and developmental basis of parasitism by plants is largely unknown. In order to investigate the process of parasitism, RNAs from different stages (i.e. seed, seedling, vegetative strand, prehaustoria, haustoria, and flower) were used to de novo assemble and annotate the transcriptome of the obligate plant stem parasite dodder (Cuscuta pentagona). The assembled transcriptome was used to dissect transcriptional dynamics during dodder development and parasitism and identified key gene categories involved in the process of plant parasitism. Host plant infection is accompanied by increased expression of parasite genes underlying transport and transporter categories, response to stress and stimuli, as well as genes encoding enzymes involved in cell wall modifications. By contrast, expression of photosynthetic genes is decreased in the dodder infective stages compared with normal stem. In addition, genes relating to biosynthesis, transport, and response of phytohormones, such as auxin, gibberellins, and strigolactone, were differentially expressed in the dodder infective stages compared with stems and seedlings. This analysis sheds light on the transcriptional changes that accompany plant parasitism and will aid in identifying potential gene targets for use in controlling the infestation of crops by parasitic weeds. © 2014 American Society of Plant Biologists. All Rights Reserved.

Toxoplasma

EPA Science Inventory

T. gondii is an obligate intracellular protozoan parasite that can infect all warm blooded animals ranging from: humans, pets, livestock, to marine aquatic animals. The definitive host is the feline species (both domestic and wild cats), where the sexual stage of the life cycle o...

Elongation Factor-1a is a novel protein associated with host cell invasion and a potential protective antigen of Cryptosporidium parvum*

USDA-ARS?s Scientific Manuscript database

The phylum Apicomplexa comprises obligate intracellular parasites that infect vertebrates. All invasive forms of Apicomplexa possess a unique complex of organelles at the anterior end, referred to as the apical complex, which is involved in host cell invasion. Previously, we generated the chicken m...

Parasite assemblages of Australian species of Pseudomys (Rodentia: Muridae: Murinae).

PubMed

Weaver, H J; Smales, L R

2012-02-01

The parasite fauna of many Australian rodents is poorly known. The ectoparasite and helminth faunas of Pseudomys delicatulus, Pseudomys desertor, Pseudomys gracilicaudatus, and Pseudomys hermannsburgensis were determined and compared. In total, 12 species of arthropods, 2 cestodes, and 13 nematodes were found. Species richness of parasites was highest in P. hermannsburgensis and lowest in P. desertor. Despite the sampling effort, the number of parasite species discovered did not reach an asymptote for any of the host species, indicating that the full parasite fauna was not examined. Helminth species richness was highest in the insectivorous P. hermannsburgensis and lower in the obligate herbivores. The structure of parasite component communities was influenced by the social structure of the host species, not surprisingly, with the most highly social species having the highest richness of parasites. Habitat preferences also provided contrast between the helminth component communities, with heligmonellid nematodes occurring in damp woodlands and dominating the parasite fauna of P. gracilicaudatus. Oxyurid nematodes dominated the component communities of the 3 other species, all of which inhabit drier habitats.

Evolution of plant parasitism in the phylum Nematoda.

PubMed

Quist, Casper W; Smant, Geert; Helder, Johannes

2015-01-01

Within the species-rich and trophically diverse phylum Nematoda, at least four independent major lineages of plant parasites have evolved, and in at least one of these major lineages plant parasitism arose independently multiple times. Ribosomal DNA data, sequence information from nematode-produced, plant cell wall-modifying enzymes, and the morphology and origin of the style(t), a protrusible piercing device used to penetrate the plant cell wall, all suggest that facultative and obligate plant parasites originate from fungivorous ancestors. Data on the nature and diversification of plant cell wall-modifying enzymes point at multiple horizontal gene transfer events from soil bacteria to bacterivorous nematodes resulting in several distinct lineages of fungal or oomycete-feeding nematodes. Ribosomal DNA frameworks with sequence data from more than 2,700 nematode taxa combined with detailed morphological information allow for explicit hypotheses on the origin of agronomically important plant parasites, such as root-knot, cyst, and lesion nematodes.

Evolution of Parasitism in Insect-transmitted Plant Nematodes

PubMed Central

Giblin-Davis, R. M.; Davies, K. A.; Morris, K.; Thomas, W. K.

2003-01-01

Nematode-insect associations have evolved many times in the phylum Nematoda, but these lineages involve plant parasitism only in the Secernentean orders Aphelenchida and Tylenchida. In the Aphelenchida (Aphelenchoidoidea), Bursaphelenchus xylophilus (Pine wood nematode), B. cocophilus (Red ring or Coconut palm nematode) (Parasitaphelenchidae), and the many potential host-specific species of Schistonchus (fig nematodes) (Aphelenchoididae) nematode-insect interactions probably evolved independently from dauer-forming, mycophagous ancestors that were phoretically transmitted to breeding sites of their insect hosts in plants. Mycophagy probably gave rise to facultative or obligate plant-parasitism because of opportunities due to insect host switches or peculiarities in host behavior. In the Tylenchida, there is one significant radiation of insect-associated plant parasites involving Fergusobia nematodes (Fergusobiinae: Neotylenchidae) and Fergusonina (Fergusoninidae) flies as mutualists that gall myrtaceous plant buds or leaves. These dicyclic nematodes have different phases that are parasitic in either the insect or the plant hosts. The evolutionary origin of this association is unclear. PMID:19265987

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures

PubMed Central

Fernandes, Maria Cecilia; Dillon, Laura A. L.; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M.

2016-01-01

ABSTRACT Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. PMID:27165796

Molecular detection and characterization of theileria spp infecting cattle in Sennar State, Sudan

USDA-ARS?s Scientific Manuscript database

Theileriosis is a serious animal disease transmitted by tick vectors. The agents of theileriosis are obligate intracellular parasites that cause mild to severe disease in the mammalian host. Tropical theileriosis has been recognized as a burden to the development of the dairy industry in Sudan and c...

Biological macromolecules based targeted nanodrug delivery systems for the treatment of intracellular infections.

PubMed

Aparna, V; Shiva, M; Biswas, Raja; Jayakumar, R

2018-04-15

Intracellular infections are tricky to treat, the reason being the poor penetration of antibiotics/antimycotics into the microbial niche (host cell). Macrophages are primary targets of facultative and obligate intracellular bacteria/fungi to be abused as host cells. The need for drugs with better intracellular penetration led to the development of endocytosable drug carriers, which can cross the cell membrane of the host cells (macrophages) by imitating the entry path of the pathogens. Therefore, the drugs can be targeted to macrophages ensuring enhanced therapeutic effect. This review discusses the exploitation of various nanocarriers for targeted delivery of drugs to the macrophages in the last two decades. Copyright © 2018 Elsevier B.V. All rights reserved.

Enforcing host cell polarity: an apicomplexan parasite strategy towards dissemination.

PubMed

Baumgartner, Martin

2011-08-01

The propagation of apicomplexan parasites through transmitting vectors is dependent on effective dissemination of parasites inside the mammalian host. Intracellular Toxoplasma and Theileria parasites face the challenge that their spread inside the host depends in part on the motile capacities of their host cells. In response, these parasites influence the efficiency of dissemination by altering adhesive and/or motile properties of their host cells. Theileria parasites do so by targeting signalling pathways that control host cell actin dynamics. The resulting enforced polar host cell morphology facilitates motility and invasiveness, by establishing focal adhesion and invasion structures at the leading edge of the infected cell. This parasite strategy highlights mechanisms of motility regulation that are also likely relevant for immune or cancer cell motility. Copyright © 2011 Elsevier Ltd. All rights reserved.

Living off a fish: a trade-off between parasites and the immune system.

PubMed

Sitjà-Bobadilla, A

2008-10-01

Research in fish immune system and parasite invasion mechanisms has advanced the knowledge of the mechanisms whereby parasites evade or cope with fish immune response. The main mechanisms of immune evasion employed by fish parasites are reviewed and considered under ten headings. 1) Parasite isolation: parasites develop in immuno-privileged host tissues, such as brain, gonads, or eyes, where host barriers prevent or limit the immune response. 2) Host isolation: the host cellular immune response isolates and encapsulates the parasites in a dormant stage without killing them. 3) Intracellular disguise: typical of intracellular microsporidians, coccidians and some myxosporeans. 4) Parasite migration, behavioural and environmental strategies: parasites migrate to host sites the immune response has not yet reached or where it is not strong enough to kill them, or they accommodate their life cycles to the season or the age in which the host immune system is down-regulated. 5) Antigen-based strategies such as mimicry or masking, variation and sharing of parasite antigens. 6) Anti-immune mechanisms: these allow parasites to resist innate humoral factors, to neutralize host antibodies or to scavenge reactive oxygen species within macrophages. 7) Immunodepression: parasites either suppress the fish immune systems by reducing the proliferative capacity of lymphocytes or the phagocytic activity of macrophages, or they induce apoptosis of host leucocytes. 8) Immunomodulation: parasites secrete or excrete substances which modulate the secretion of host immune factors, such as cytokines, to their own benefit. 9) Fast development: parasites proliferate faster than the ability of the host to mount a defence response. 10) Exploitation of the host immune reaction. Knowledge of the evasion strategies adopted by parasites will help us to understand host-parasite interactions and may therefore help in the discovery of novel immunotherapeutic agents or targeted vaccines, and permit the

Genomics of apicomplexan parasites.

PubMed

Swapna, Lakshmipuram Seshadri; Parkinson, John

2017-06-01

The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively) represent a significant global healthcare burden. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To lay the foundation for programs of drug discovery and vaccine development, genome sequences for many of these organisms have been generated, together with large-scale expression and proteomic datasets. Comparative analyses of these datasets are beginning to identify the molecular innovations supporting both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage-specific adaptations associated with divergent life-cycle strategies. The challenge is how best to exploit these data to derive insights into parasite virulence and identify those genes representing the most amenable targets. In this review, we outline genomic datasets currently available for apicomplexans and discuss biological insights that have emerged as a consequence of their analysis. Of particular interest are systems-based resources, focusing on areas of metabolism and host invasion that are opening up opportunities for discovering new therapeutic targets.

Social Hackers: Integration in the Host Chemical Recognition System by a Paper Wasp Social Parasite

NASA Astrophysics Data System (ADS)

Turillazzi, S.; Sledge, M. F.; Dani, F. R.; Cervo, R.; Massolo, A.; Fondelli, L.

Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.

Social hackers: integration in the host chemical recognition system by a paper wasp social parasite.

PubMed

Turillazzi, S; Sledge, M F; Dani, F R; Cervo, R; Massolo, A; Fondelli, L

2000-04-01

Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.

Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence.

PubMed

Brown, Robert W B; Sharma, Aabha I; Engman, David M

2017-04-01

Eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. Protein S-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (PAT) and can be removed by lysosomal palmitoyl-protein thioesterase (PPT) or cytosolic acyl-protein thioesterase (APT). In addition to anchoring proteins to intracellular membranes, functions of dynamic palmitoylation include - targeting proteins to specific intracellular compartments via trafficking pathways, regulating the cycling of proteins between membranes, modulating protein function and regulating protein stability. Recent studies in the eukaryotic parasites - Plasmodium falciparum, Toxoplasma gondii, Trypanosoma brucei, Cryptococcus neoformans and Giardia lamblia - have identified large families of PATs and palmitoylated proteins. Many palmitoylated proteins are important for diverse aspects of pathogenesis, including differentiation into infective life cycle stages, biogenesis and tethering of secretory organelles, assembling the machinery powering motility and targeting virulence factors to the plasma membrane. This review aims to summarize our current knowledge of palmitoylation in eukaryotic parasites, highlighting five exemplary mechanisms of parasite virulence dependent on palmitoylation.

Obliging children.

PubMed

Lyons, Barry

2011-01-01

Children may sometimes undergo healthcare procedures that are not intended to improve their health status. Such interventions might include the use of young children as bone marrow donors or their enrolment in non-therapeutic research. One of the justifications used to legitimise these interventions is the premise that children have obligations to others; to their family in the case of related bone marrow transplantation, and to wider society in the case of non-therapeutic research. However, this 'obligation model' (the notion that children possess positive obligations to advance the health status of others) fails as a justificatory paradigm because it is based upon a confusion, identified by Hart, between two notions; that of 'being under an obligation to do something' and that of 'being obliged to do something'. Instead the 'obligation model' is a device employed to put a justificatory gloss upon a consequentialist decision-making process; removing the legitimising gloss allows for a more transparent look at the conflict between parental rights and an individual child's right to bodily integrity.

Fluorogenic Substrate Detection of Viable Intracellular and Extracellular Pathogenic Protozoa

NASA Astrophysics Data System (ADS)

Jackson, Peter R.; Pappas, Michael G.; Hansen, Brian D.

1985-01-01

Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells. This procedure is superior to other assays because it is faster and detects viable intracellular as well as extracellular Leishmania. Furthermore, destruction of intracellular pathogens by macrophages is more accurately determined with fluorescein diacetate than with other stains. The procedure may have applications in programs to develop drugs and vaccines against protozoa responsible for human and animal disease.

Mechanisms of CNS invasion and damage by parasites.

PubMed

Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

2013-01-01

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Membrane transport in the malaria parasite and its host erythrocyte.

PubMed

Kirk, Kiaran; Lehane, Adele M

2014-01-01

As it grows and replicates within the erythrocytes of its host the malaria parasite takes up nutrients from the extracellular medium, exports metabolites and maintains a tight control over its internal ionic composition. These functions are achieved via membrane transport proteins, integral membrane proteins that mediate the passage of solutes across the various membranes that separate the biochemical machinery of the parasite from the extracellular environment. Proteins of this type play a key role in antimalarial drug resistance, as well as being candidate drug targets in their own right. This review provides an overview of recent work on the membrane transport biology of the malaria parasite-infected erythrocyte, encompassing both the parasite-induced changes in the membrane transport properties of the host erythrocyte and the cell physiology of the intracellular parasite itself.

Nutrient sensing modulates malaria parasite virulence

PubMed Central

Mancio-Silva, Liliana; Slavic, Ksenija; Grilo Ruivo, Margarida T.; Grosso, Ana Rita; Modrzynska, Katarzyna K.; Vera, Iset Medina; Sales-Dias, Joana; Gomes, Ana Rita; MacPherson, Cameron Ross; Crozet, Pierre; Adamo, Mattia; Baena-Gonzalez, Elena; Tewari, Rita; Llinás, Manuel; Billker, Oliver; Mota, Maria M.

2017-01-01

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host(s), primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signaling networks that confer to cells the ability to sense and adapt to varying environmental conditions1,2. Canonical nutrient-sensing pathways are presumably absent in the causing agent of malaria Plasmodium3–5, thus raising the question of whether these parasites possess the capacity to sense and cope with host nutrient fluctuations. Here, we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through a rearrangement of their transcriptome accompanied by a significant adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology to SNF1/AMPKα and yeast complementation studies suggest functional conservation of an ancient cellular energy sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical to modulate parasite replication and virulence. PMID:28678779

Nutrient sensing modulates malaria parasite virulence.

PubMed

Mancio-Silva, Liliana; Slavic, Ksenija; Grilo Ruivo, Margarida T; Grosso, Ana Rita; Modrzynska, Katarzyna K; Vera, Iset Medina; Sales-Dias, Joana; Gomes, Ana Rita; MacPherson, Cameron Ross; Crozet, Pierre; Adamo, Mattia; Baena-Gonzalez, Elena; Tewari, Rita; Llinás, Manuel; Billker, Oliver; Mota, Maria M

2017-07-13

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence.

Dramatic transcriptional changes in an intracellular parasite enable host switching between plant and insect.

PubMed

Oshima, Kenro; Ishii, Yoshiko; Kakizawa, Shigeyuki; Sugawara, Kyoko; Neriya, Yutaro; Himeno, Misako; Minato, Nami; Miura, Chihiro; Shiraishi, Takuya; Yamaji, Yasuyuki; Namba, Shigetou

2011-01-01

Phytoplasmas are bacterial plant pathogens that have devastating effects on the yields of crops and plants worldwide. They are intracellular parasites of both plants and insects, and are spread among plants by insects. How phytoplasmas can adapt to two diverse environments is of considerable interest; however, the mechanisms enabling the "host switching" between plant and insect hosts are poorly understood. Here, we report that phytoplasmas dramatically alter their gene expression in response to "host switching" between plant and insect. We performed a detailed characterization of the dramatic change that occurs in the gene expression profile of Candidatus Phytoplasma asteris OY-M strain (approximately 33% of the genes change) upon host switching between plant and insect. The phytoplasma may use transporters, secreted proteins, and metabolic enzymes in a host-specific manner. As phytoplasmas reside within the host cell, the proteins secreted from phytoplasmas are thought to play crucial roles in the interplay between phytoplasmas and host cells. Our microarray analysis revealed that the expression of the gene encoding the secreted protein PAM486 was highly upregulated in the plant host, which is also observed by immunohistochemical analysis, suggesting that this protein functions mainly when the phytoplasma grows in the plant host. Additionally, phytoplasma growth in planta was partially suppressed by an inhibitor of the MscL osmotic channel that is highly expressed in the plant host, suggesting that the osmotic channel might play an important role in survival in the plant host. These results also suggest that the elucidation of "host switching" mechanism may contribute to the development of novel pest controls.

Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection

PubMed Central

Nishi, Manami; El-Hage, Sandy; Fox, Barbara A.; Bzik, David J.

2015-01-01

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4+ T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, namely, the MHC-II-associated invariant chain (Ii or CD74) and the peptide editor H2-DM, in professional antigen-presenting cells (pAPCs). Genetic deletion of CD74 restored the ability of infected dendritic cells to present a parasite antigen in the context of MHC-II in vitro. CD74 mRNA and protein levels were, surprisingly, elevated in infected cells, whereas MHC-II and H2-DM expression was inhibited. CD74 accumulated mainly in the endoplasmic reticulum (ER), and this phenotype required live parasites, but not active replication. Finally, we compared the impacts of genetic deletion of CD74 and H2-DM genes on parasite dissemination toward lymphoid organs in mice, as well as activation of CD4+ T cells and interferon gamma (IFN-γ) levels during acute infection. Cyst burdens and survival during the chronic phase of infection were also evaluated in wild-type and knockout mice. These results highlight the fact that the infection is influenced by multiple levels of parasite manipulation of the MHC-II antigen presentation pathway. PMID:26195549

De Novo Assembly and Characterization of the Transcriptome of the Parasitic Weed Dodder Identifies Genes Associated with Plant Parasitism1[C][W][OPEN

PubMed Central

Ranjan, Aashish; Ichihashi, Yasunori; Farhi, Moran; Zumstein, Kristina; Townsley, Brad; David-Schwartz, Rakefet; Sinha, Neelima R.

2014-01-01

Parasitic flowering plants are one of the most destructive agricultural pests and have major impact on crop yields throughout the world. Being dependent on finding a host plant for growth, parasitic plants penetrate their host using specialized organs called haustoria. Haustoria establish vascular connections with the host, which enable the parasite to steal nutrients and water. The underlying molecular and developmental basis of parasitism by plants is largely unknown. In order to investigate the process of parasitism, RNAs from different stages (i.e. seed, seedling, vegetative strand, prehaustoria, haustoria, and flower) were used to de novo assemble and annotate the transcriptome of the obligate plant stem parasite dodder (Cuscuta pentagona). The assembled transcriptome was used to dissect transcriptional dynamics during dodder development and parasitism and identified key gene categories involved in the process of plant parasitism. Host plant infection is accompanied by increased expression of parasite genes underlying transport and transporter categories, response to stress and stimuli, as well as genes encoding enzymes involved in cell wall modifications. By contrast, expression of photosynthetic genes is decreased in the dodder infective stages compared with normal stem. In addition, genes relating to biosynthesis, transport, and response of phytohormones, such as auxin, gibberellins, and strigolactone, were differentially expressed in the dodder infective stages compared with stems and seedlings. This analysis sheds light on the transcriptional changes that accompany plant parasitism and will aid in identifying potential gene targets for use in controlling the infestation of crops by parasitic weeds. PMID:24399359

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

PubMed

Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

2016-05-10

Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in

Genetic and immunological comparison of the cladoceran parasite Pasteuria ramosa with the nematode parasite Pasteuria penetrans.

PubMed

Schmidt, Liesbeth M; Mouton, Laurence; Nong, Guang; Ebert, Dieter; Preston, James F

2008-01-01

Pasteuria penetrans, an obligate endospore-forming parasite of Meloidogyne spp. (root knot nematodes), has been identified as a promising agent for biocontrol of these destructive agricultural crop pests. Pasteuria ramosa, an obligate parasite of water fleas (Daphnia spp.), has been shown to modulate cladoceran populations in natural ecosystems. Selected sporulation genes and an epitope associated with the spore envelope of these related species were compared. The sigE and spoIIAA/spoIIAB genes differentiate the two species to a greater extent than 16S rRNA and may serve as probes to differentiate the species. Single-nucleotide variations were observed in several conserved genes of five distinct populations of P. ramosa, and while most of these variations are silent single-nucleotide polymorphisms, a few result in conservative amino acid substitutions. A monoclonal antibody directed against an adhesin epitope present on P. penetrans P20 endospores, previously determined to be specific for Pasteuria spp. associated with several phytopathogenic nematodes, also detects an epitope associated with P. ramosa endospores. Immunoblotting provided patterns that differentiate P. ramosa from other Pasteuria spp. This monoclonal antibody thus provides a probe with which to detect and discriminate endospores of different Pasteuria spp. The presence of a shared adhesin epitope in two species with such ecologically distant hosts suggests that there is an ancient and ecologically significant recognition process in these endospore-forming bacilli that contributes to the virulence of both species in their respective hosts.

Genetic and Immunological Comparison of the Cladoceran Parasite Pasteuria ramosa with the Nematode Parasite Pasteuria penetrans▿

PubMed Central

Schmidt, Liesbeth M.; Mouton, Laurence; Nong, Guang; Ebert, Dieter; Preston, James F.

2008-01-01

Pasteuria penetrans, an obligate endospore-forming parasite of Meloidogyne spp. (root knot nematodes), has been identified as a promising agent for biocontrol of these destructive agricultural crop pests. Pasteuria ramosa, an obligate parasite of water fleas (Daphnia spp.), has been shown to modulate cladoceran populations in natural ecosystems. Selected sporulation genes and an epitope associated with the spore envelope of these related species were compared. The sigE and spoIIAA/spoIIAB genes differentiate the two species to a greater extent than 16S rRNA and may serve as probes to differentiate the species. Single-nucleotide variations were observed in several conserved genes of five distinct populations of P. ramosa, and while most of these variations are silent single-nucleotide polymorphisms, a few result in conservative amino acid substitutions. A monoclonal antibody directed against an adhesin epitope present on P. penetrans P20 endospores, previously determined to be specific for Pasteuria spp. associated with several phytopathogenic nematodes, also detects an epitope associated with P. ramosa endospores. Immunoblotting provided patterns that differentiate P. ramosa from other Pasteuria spp. This monoclonal antibody thus provides a probe with which to detect and discriminate endospores of different Pasteuria spp. The presence of a shared adhesin epitope in two species with such ecologically distant hosts suggests that there is an ancient and ecologically significant recognition process in these endospore-forming bacilli that contributes to the virulence of both species in their respective hosts. PMID:17933927

An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum.

PubMed

Henry, Roselani I; Cobbold, Simon A; Allen, Richard J W; Khan, Asif; Hayward, Rhys; Lehane, Adele M; Bray, Patrick G; Howitt, Susan M; Biagini, Giancarlo A; Saliba, Kevin J; Kirk, Kiaran

2010-06-11

The intraerythrocytic malaria parasite exerts tight control over its ionic composition. In this study, a combination of fluorescent ion indicators and (36)Cl(-) flux measurements was used to investigate the transport of Cl(-) and the Cl(-)-dependent transport of "H(+)-equivalents" in mature (trophozoite stage) parasites, isolated from their host erythrocytes. Removal of extracellular Cl(-), resulting in an outward [Cl(-)] gradient, gave rise to a cytosolic alkalinization (i.e. a net efflux of H(+)-equivalents). This was reversed on restoration of extracellular Cl(-). The flux of H(+)-equivalents was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and, when measured in ATP-depleted parasites, showed a pronounced dependence on the pH of the parasite cytosol; the flux was low at cytosolic pH values < 7.2 but increased steeply with cytosolic pH at values > 7.2. (36)Cl(-) influx measurements revealed the presence of a Cl(-) uptake mechanism with characteristics similar to those of the Cl(-)-dependent H(+)-equivalent flux. The intracellular concentration of Cl(-) in the parasite was estimated to be approximately 48 mm in situ. The data are consistent with the intraerythrocytic parasite having in its plasma membrane a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive transporter that, under physiological conditions, imports Cl(-) together with H(+)-equivalents, resulting in an intracellular Cl(-) concentration well above that which would occur if Cl(-) ions were distributed passively in accordance with the parasite's large, inwardly negative membrane potential.

The Dialogue of the Host-Parasite Relationship: Leishmania spp. and Trypanosoma cruzi Infection.

PubMed

de Morais, Carlos Gustavo Vieira; Castro Lima, Ana Karina; Terra, Rodrigo; dos Santos, Rosiane Freire; Da-Silva, Silvia Amaral Gonçalves; Dutra, Patrícia Maria Lourenço

2015-01-01

The intracellular protozoa Leishmania spp. and Trypanosoma cruzi and the causative agents of Leishmaniasis and Chagas disease, respectively, belong to the Trypanosomatidae family. Together, these two neglected tropical diseases affect approximately 25 million people worldwide. Whether the host can control the infection or develops disease depends on the complex interaction between parasite and host. Parasite surface and secreted molecules are involved in triggering specific signaling pathways essential for parasite entry and intracellular survival. The recognition of the parasite antigens by host immune cells generates a specific immune response. Leishmania spp. and T. cruzi have a multifaceted repertoire of strategies to evade or subvert the immune system by interfering with a range of signal transduction pathways in host cells, which causes the inhibition of the protective response and contributes to their persistence in the host. The current therapeutic strategies in leishmaniasis and trypanosomiasis are very limited. Efficacy is variable, toxicity is high, and the emergence of resistance is increasingly common. In this review, we discuss the molecular basis of the host-parasite interaction of Leishmania and Trypanosoma cruzi infection and their mechanisms of subverting the immune response and how this knowledge can be used as a tool for the development of new drugs.

The Dialogue of the Host-Parasite Relationship: Leishmania spp. and Trypanosoma cruzi Infection

PubMed Central

de Morais, Carlos Gustavo Vieira; Castro Lima, Ana Karina; dos Santos, Rosiane Freire; Da-Silva, Silvia Amaral Gonçalves; Dutra, Patrícia Maria Lourenço

2015-01-01

The intracellular protozoa Leishmania spp. and Trypanosoma cruzi and the causative agents of Leishmaniasis and Chagas disease, respectively, belong to the Trypanosomatidae family. Together, these two neglected tropical diseases affect approximately 25 million people worldwide. Whether the host can control the infection or develops disease depends on the complex interaction between parasite and host. Parasite surface and secreted molecules are involved in triggering specific signaling pathways essential for parasite entry and intracellular survival. The recognition of the parasite antigens by host immune cells generates a specific immune response. Leishmania spp. and T. cruzi have a multifaceted repertoire of strategies to evade or subvert the immune system by interfering with a range of signal transduction pathways in host cells, which causes the inhibition of the protective response and contributes to their persistence in the host. The current therapeutic strategies in leishmaniasis and trypanosomiasis are very limited. Efficacy is variable, toxicity is high, and the emergence of resistance is increasingly common. In this review, we discuss the molecular basis of the host-parasite interaction of Leishmania and Trypanosoma cruzi infection and their mechanisms of subverting the immune response and how this knowledge can be used as a tool for the development of new drugs. PMID:26090399

Leishmania hijacking of the macrophage intracellular compartments.

PubMed

Liévin-Le Moal, Vanessa; Loiseau, Philippe M

2016-02-01

Leishmania spp., transmitted to humans by the bite of the sandfly vector, are responsible for the three major forms of leishmaniasis, cutaneous, diffuse mucocutaneous and visceral. Leishmania spp. interact with membrane receptors of neutrophils and macrophages. In macrophages, the parasite is internalized within a parasitophorous vacuole and engages in a particular intracellular lifestyle in which the flagellated, motile Leishmania promastigote metacyclic form differentiates into non-motile, metacyclic amastigote form. This phenomenon is induced by Leishmania-triggered events leading to the fusion of the parasitophorous vacuole with vesicular members of the host cell endocytic pathway including recycling endosomes, late endosomes and the endoplasmic reticulum. Maturation of the parasitophorous vacuole leads to the intracellular proliferation of the Leishmania amastigote forms by acquisition of host cell nutrients while escaping host defense responses. © 2015 FEBS.

Co-extinction in a host-parasite network: identifying key hosts for network stability.

PubMed

Dallas, Tad; Cornelius, Emily

2015-08-17

Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability.

Host-parasite coevolution beyond the nestling stage? Mimicry of host fledglings by the specialist screaming cowbird.

PubMed

De Mársico, María C; Gantchoff, Mariela G; Reboreda, Juan C

2012-09-07

Egg mimicry by obligate avian brood parasites and host rejection of non-mimetic eggs are well-known textbook examples of host-parasite coevolution. By contrast, reciprocal adaptations and counteradaptations beyond the egg stage in brood parasites and their hosts have received less attention. The screaming cowbird (Molothrus rufoaxillaris) is a specialist obligate brood parasite whose fledglings look identical to those of its primary host, the baywing (Agelaioides badius). Such a resemblance has been proposed as an adaptation in response to host discrimination against odd-looking young, but evidence supporting this idea is scarce. Here, we examined this hypothesis by comparing the survival rates of young screaming cowbirds and non-mimetic shiny cowbirds (Molothrus bonariensis) cross-fostered to baywing nests and quantifying the similarity in plumage colour and begging calls between host and cowbird fledglings. Shiny cowbirds suffered higher post-fledging mortality rates (83%) than screaming cowbirds (0%) owing to host rejection. Visual modelling revealed that screaming cowbirds, but not shiny cowbirds, were indistinguishable from host young in plumage colour. Similarly, screaming cowbirds matched baywings' begging calls more closely than shiny cowbirds. Our results strongly support the occurrence of host fledgling mimicry in screaming cowbirds and suggest a role of visual and vocal cues in fledgling discrimination by baywings.

Host–parasite coevolution beyond the nestling stage? Mimicry of host fledglings by the specialist screaming cowbird

PubMed Central

De Mársico, María C.; Gantchoff, Mariela G.; Reboreda, Juan C.

2012-01-01

Egg mimicry by obligate avian brood parasites and host rejection of non-mimetic eggs are well-known textbook examples of host–parasite coevolution. By contrast, reciprocal adaptations and counteradaptations beyond the egg stage in brood parasites and their hosts have received less attention. The screaming cowbird (Molothrus rufoaxillaris) is a specialist obligate brood parasite whose fledglings look identical to those of its primary host, the baywing (Agelaioides badius). Such a resemblance has been proposed as an adaptation in response to host discrimination against odd-looking young, but evidence supporting this idea is scarce. Here, we examined this hypothesis by comparing the survival rates of young screaming cowbirds and non-mimetic shiny cowbirds (Molothrus bonariensis) cross-fostered to baywing nests and quantifying the similarity in plumage colour and begging calls between host and cowbird fledglings. Shiny cowbirds suffered higher post-fledging mortality rates (83%) than screaming cowbirds (0%) owing to host rejection. Visual modelling revealed that screaming cowbirds, but not shiny cowbirds, were indistinguishable from host young in plumage colour. Similarly, screaming cowbirds matched baywings' begging calls more closely than shiny cowbirds. Our results strongly support the occurrence of host fledgling mimicry in screaming cowbirds and suggest a role of visual and vocal cues in fledgling discrimination by baywings. PMID:22648157

Gene transfer from a parasitic flowering plant to a fern

PubMed Central

Davis, Charles C; Anderson, William R; Wurdack, Kenneth J

2005-01-01

The rattlesnake fern (Botrychium virginianum (L.) Sw.) is obligately mycotrophic and widely distributed across the northern hemisphere. Three mitochondrial gene regions place this species with other ferns in Ophioglossaceae, while two regions place it as a member of the largely parasitic angiosperm order Santalales (sandalwoods and mistletoes). These discordant phylogenetic placements suggest that part of the genome in B. virginianum was acquired by horizontal gene transfer (HGT), perhaps from root-parasitic Loranthaceae. These transgenes are restricted to B. virginianum and occur across the range of the species. Molecular and life-history traits indicate that the transfer preceded the global expansion of B. virginianum, and that the latter may have happened very rapidly. This is the first report of HGT from an angiosperm to a fern, through either direct parasitism or the mediation of interconnecting fungal symbionts. PMID:16191635

Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites.

PubMed

Mina, John G; Thye, Julie K; Alqaisi, Amjed Q I; Bird, Louise E; Dods, Robert H; Grøftehauge, Morten K; Mosely, Jackie A; Pratt, Steven; Shams-Eldin, Hosam; Schwarz, Ralph T; Pohl, Ehmke; Denny, Paul W

2017-07-21

Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation, and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis: the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Similar evolutionary potentials in an obligate ant parasite and its two host species

PubMed Central

Pennings, P S; Achenbach, A; Foitzik, S

2011-01-01

The spatial structure of host–parasite coevolution is shaped by population structure and genetic diversity of the interacting species. We analysed these population genetic parameters in three related ant species: the parasitic slavemaking ant Protomognathus americanus and its two host species Temnothorax longispinosus and T. curvispinosus. We sampled throughout their range, genotyped ants on six to eight microsatellite loci and an MtDNA sequence and found high levels of genetic variation and strong population structure in all three species. Interestingly, the most abundant species and primary host, T. longispinosus, is characterized by less structure, but lower local genetic diversity. Generally, differences between the species were small, and we conclude that they have similar evolutionary potentials. The coevolutionary interaction between this social parasite and its hosts may therefore be less influenced by divergent evolutionary potentials, but rather by varying selection pressures. We employed different methods to quantify and compare genetic diversity and structure between species and genetic markers. We found that Jost D is well suited for these comparisons, as long as mutation rates between markers and species are similar. If this is not the case, for example, when using MtDNA and microsatellites to study sex-specific dispersal, model-based inference should be used instead of descriptive statistics (such as D or GST). Using coalescent-based methods, we indeed found that males disperse much more than females, but this sex bias in dispersal differed between species. The findings of the different approaches with regard to genetic diversity and structure were in good accordance with each other. PMID:21324025

Dramatic Transcriptional Changes in an Intracellular Parasite Enable Host Switching between Plant and Insect

PubMed Central

Oshima, Kenro; Ishii, Yoshiko; Kakizawa, Shigeyuki; Sugawara, Kyoko; Neriya, Yutaro; Himeno, Misako; Minato, Nami; Miura, Chihiro; Shiraishi, Takuya; Yamaji, Yasuyuki; Namba, Shigetou

2011-01-01

Phytoplasmas are bacterial plant pathogens that have devastating effects on the yields of crops and plants worldwide. They are intracellular parasites of both plants and insects, and are spread among plants by insects. How phytoplasmas can adapt to two diverse environments is of considerable interest; however, the mechanisms enabling the “host switching” between plant and insect hosts are poorly understood. Here, we report that phytoplasmas dramatically alter their gene expression in response to “host switching” between plant and insect. We performed a detailed characterization of the dramatic change that occurs in the gene expression profile of Candidatus Phytoplasma asteris OY-M strain (approximately 33% of the genes change) upon host switching between plant and insect. The phytoplasma may use transporters, secreted proteins, and metabolic enzymes in a host-specific manner. As phytoplasmas reside within the host cell, the proteins secreted from phytoplasmas are thought to play crucial roles in the interplay between phytoplasmas and host cells. Our microarray analysis revealed that the expression of the gene encoding the secreted protein PAM486 was highly upregulated in the plant host, which is also observed by immunohistochemical analysis, suggesting that this protein functions mainly when the phytoplasma grows in the plant host. Additionally, phytoplasma growth in planta was partially suppressed by an inhibitor of the MscL osmotic channel that is highly expressed in the plant host, suggesting that the osmotic channel might play an important role in survival in the plant host. These results also suggest that the elucidation of “host switching” mechanism may contribute to the development of novel pest controls. PMID:21858041

Imaging host cell-Leishmania interaction dynamics implicates parasite motility, lysosome recruitment, and host cell wounding in the infection process.

PubMed

Forestier, Claire-Lise; Machu, Christophe; Loussert, Celine; Pescher, Pascale; Späth, Gerald F

2011-04-21

Leishmania donovani causes human visceral leishmaniasis. The parasite infectious cycle comprises extracellular flagellated promastigotes that proliferate inside the insect vector, and intracellular nonmotile amastigotes that multiply within infected host cells. Using primary macrophages infected with virulent metacyclic promastigotes and high spatiotemporal resolution microscopy, we dissect the dynamics of the early infection process. We find that motile promastigotes enter macrophages in a polarized manner through their flagellar tip and are engulfed into host lysosomal compartments. Persistent intracellular flagellar activity leads to reorientation of the parasite flagellum toward the host cell periphery and results in oscillatory parasite movement. The latter is associated with local lysosomal exocytosis and host cell plasma membrane wounding. These findings implicate lysosome recruitment followed by lysosome exocytosis, consistent with parasite-driven host cell injury, as key cellular events in Leishmania host cell infection. This work highlights the role of promastigote polarity and motility during parasite entry. Copyright © 2011 Elsevier Inc. All rights reserved.

Host–parasite genotypic interactions in the honey bee: the dynamics of diversity

PubMed Central

Evison, Sophie E F; Fazio, Geraldine; Chappell, Paula; Foley, Kirsten; Jensen, Annette B; Hughes, William O H

2013-01-01

Parasites are thought to be a major driving force shaping genetic variation in their host, and are suggested to be a significant reason for the maintenance of sexual reproduction. A leading hypothesis for the occurrence of multiple mating (polyandry) in social insects is that the genetic diversity generated within-colonies through this behavior promotes disease resistance. This benefit is likely to be particularly significant when colonies are exposed to multiple species and strains of parasites, but host–parasite genotypic interactions in social insects are little known. We investigated this using honey bees, which are naturally polyandrous and consequently produce genetically diverse colonies containing multiple genotypes (patrilines), and which are also known to host multiple strains of various parasite species. We found that host genotypes differed significantly in their resistance to different strains of the obligate fungal parasite that causes chalkbrood disease, while genotypic variation in resistance to the facultative fungal parasite that causes stonebrood disease was less pronounced. Our results show that genetic variation in disease resistance depends in part on the parasite genotype, as well as species, with the latter most likely relating to differences in parasite life history and host–parasite coevolution. Our results suggest that the selection pressure from genetically diverse parasites might be an important driving force in the evolution of polyandry, a mechanism that generates significant genetic diversity in social insects. PMID:23919163

Host-parasite genotypic interactions in the honey bee: the dynamics of diversity.

PubMed

Evison, Sophie E F; Fazio, Geraldine; Chappell, Paula; Foley, Kirsten; Jensen, Annette B; Hughes, William O H

2013-07-01

Parasites are thought to be a major driving force shaping genetic variation in their host, and are suggested to be a significant reason for the maintenance of sexual reproduction. A leading hypothesis for the occurrence of multiple mating (polyandry) in social insects is that the genetic diversity generated within-colonies through this behavior promotes disease resistance. This benefit is likely to be particularly significant when colonies are exposed to multiple species and strains of parasites, but host-parasite genotypic interactions in social insects are little known. We investigated this using honey bees, which are naturally polyandrous and consequently produce genetically diverse colonies containing multiple genotypes (patrilines), and which are also known to host multiple strains of various parasite species. We found that host genotypes differed significantly in their resistance to different strains of the obligate fungal parasite that causes chalkbrood disease, while genotypic variation in resistance to the facultative fungal parasite that causes stonebrood disease was less pronounced. Our results show that genetic variation in disease resistance depends in part on the parasite genotype, as well as species, with the latter most likely relating to differences in parasite life history and host-parasite coevolution. Our results suggest that the selection pressure from genetically diverse parasites might be an important driving force in the evolution of polyandry, a mechanism that generates significant genetic diversity in social insects.

Host responses to interspecific brood parasitism: a by-product of adaptations to conspecific parasitism?

PubMed Central

2014-01-01

Background Why have birds evolved the ability to reject eggs? Typically, foreign egg discrimination is interpreted as evidence that interspecific brood parasitism (IP) has selected for the host’s ability to recognize and eliminate foreign eggs. Fewer studies explore the alternative hypothesis that rejection of interspecific eggs is a by-product of host defenses, evolved against conspecific parasitism (CP). We performed a large scale study with replication across taxa (two congeneric Turdus thrushes), space (populations), time (breeding seasons), and treatments (three types of experimental eggs), using a consistent design of egg rejection experiments (n = 1057 nests; including controls), in areas with potential IP either present (Europe; native populations) or absent (New Zealand; introduced populations). These comparisons benefited from the known length of allopatry (one and a half centuries), with no gene flow between native and introduced populations, which is rarely available in host-parasite systems. Results Hosts rejected CP at unusually high rates for passerines (up to 60%). CP rejection rates were higher in populations with higher conspecific breeding densities and no risks of IP, supporting the CP hypothesis. IP rejection rates did not covary geographically with IP risk, contradicting the IP hypothesis. High egg rejection rates were maintained in the relatively long-term isolation from IP despite non-trivial rejection costs and errors. Conclusions These egg rejection patterns, combined with recent findings that these thrushes are currently unsuitable hosts of the obligate parasitic common cuckoo (Cuculus canorus), are in agreement with the hypothesis that the rejection of IP is a by-product of fine-tuned egg discrimination evolved due to CP. Our study highlights the importance of considering both IP and CP simultaneously as potential drivers in the evolution of egg discrimination, and illustrates how populations introduced to novel ecological contexts

Host responses to interspecific brood parasitism: a by-product of adaptations to conspecific parasitism?

PubMed

Samas, Peter; Hauber, Mark E; Cassey, Phillip; Grim, Tomas

2014-01-01

Why have birds evolved the ability to reject eggs? Typically, foreign egg discrimination is interpreted as evidence that interspecific brood parasitism (IP) has selected for the host's ability to recognize and eliminate foreign eggs. Fewer studies explore the alternative hypothesis that rejection of interspecific eggs is a by-product of host defenses, evolved against conspecific parasitism (CP). We performed a large scale study with replication across taxa (two congeneric Turdus thrushes), space (populations), time (breeding seasons), and treatments (three types of experimental eggs), using a consistent design of egg rejection experiments (n = 1057 nests; including controls), in areas with potential IP either present (Europe; native populations) or absent (New Zealand; introduced populations). These comparisons benefited from the known length of allopatry (one and a half centuries), with no gene flow between native and introduced populations, which is rarely available in host-parasite systems. Hosts rejected CP at unusually high rates for passerines (up to 60%). CP rejection rates were higher in populations with higher conspecific breeding densities and no risks of IP, supporting the CP hypothesis. IP rejection rates did not covary geographically with IP risk, contradicting the IP hypothesis. High egg rejection rates were maintained in the relatively long-term isolation from IP despite non-trivial rejection costs and errors. These egg rejection patterns, combined with recent findings that these thrushes are currently unsuitable hosts of the obligate parasitic common cuckoo (Cuculus canorus), are in agreement with the hypothesis that the rejection of IP is a by-product of fine-tuned egg discrimination evolved due to CP. Our study highlights the importance of considering both IP and CP simultaneously as potential drivers in the evolution of egg discrimination, and illustrates how populations introduced to novel ecological contexts can provide critical insights

Impact of micro-environmental changes on respiratory tract infections with intracellular bacteria.

PubMed

Shima, Kensuke; Coopmeiners, Jonas; Graspeuntner, Simon; Dalhoff, Klaus; Rupp, Jan

2016-11-01

Community-acquired pneumonia is caused by intra- and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon-γ levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body. © 2016 Federation of European Biochemical Societies.

The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery.

PubMed

Lamotte, Suzanne; Späth, Gerald F; Rachidi, Najma; Prina, Eric

2017-06-01

The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host-parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.

Nest destruction elicits indiscriminate con- versus heterospecific brood parasitism in a captive bird.

PubMed

Shaw, Rachael C; Feeney, William E; Hauber, Mark E

2014-12-01

Following nest destruction, the laying of physiologically committed eggs (eggs that are ovulated, yolked, and making their way through the oviduct) in the nests of other birds is considered a viable pathway for the evolution of obligate interspecific brood parasitism. While intraspecific brood parasitism in response to nest predation has been experimentally demonstrated, this pathway has yet to be evaluated in an interspecific context. We studied patterns of egg laying following experimental nest destruction in captive zebra finches, Taeniopygia guttata, a frequent intraspecific brood parasite. We found that zebra finches laid physiologically committed eggs indiscriminately between nests containing conspecific eggs and nests containing heterospecific eggs (of Bengalese finches, Lonchura striata vars. domestica), despite the con- and heterospecific eggs differing in both size and coloration. This is the first experimental evidence that nest destruction may provide a pathway for the evolution of interspecific brood parasitism in birds.

Mi Casa es Su Casa: how an intracellular symbiont manipulates host biology.

PubMed

Bhattacharya, Tamanash; Newton, Irene L G

2017-10-27

Wolbachia pipientis, the most common intracellular infection on the planet, infects 40% of insects as well as nematodes, isopods and arachnids. Wolbachia are obligately intracellular and challenging to study; there are no genetic tools for manipulating Wolbachia nor can they be cultured outside of host cells. Despite these roadblocks, the research community has defined a set of Wolbachia loci involved in host interaction: Wolbachia effectors. Through the use of Drosophila genetics, surrogate systems and biochemistry, the field has begun to define the toolkit Wolbachia use for host manipulation. Below we review recent findings identifying these Wolbachia effectors and point to potential, as yet uncharacterized, links between known phenotypes induced by Wolbachia infection and predicted effectors. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Settling Down: The Genome of Serratia symbiotica from the Aphid Cinara tujafilina Zooms in on the Process of Accommodation to a Cooperative Intracellular Life

PubMed Central

Manzano-Marín, Alejandro; Latorre, Amparo

2014-01-01

Particularly interesting cases of mutualistic endosymbioses come from the establishment of co-obligate associations of more than one species of endosymbiotic bacteria. Throughout symbiotic accommodation from a free-living bacterium, passing through a facultative stage and ending as an obligate intracellular one, the symbiont experiences massive genomic losses and phenotypic adjustments. Here, we scrutinized the changes in the coevolution of Serratia symbiotica and Buchnera aphidicola endosymbionts in aphids, paying particular attention to the transformations undergone by S. symbiotica to become an obligate endosymbiont. Although it is already known that S. symbiotica is facultative in Acyrthosiphon pisum, in Cinara cedri it has established a co-obligate endosymbiotic consortium along with B. aphidicola to fulfill the aphid’s nutritional requirements. The state of this association in C. tujafilina, an aphid belonging to the same subfamily (Lachninae) that C. cedri, remained unknown. Here, we report the genome of S. symbiotica strain SCt-VLC from the aphid C. tujafilina. While being phylogenetically and genomically very closely related to the facultative endosymbiont S. symbiotica from the aphid A. pisum, it shows a variety of metabolic, genetic, and architectural features, which point toward this endosymbiont being one step closer to an obligate intracellular one. We also describe in depth the process of genome rearrangements suffered by S. symbiotica and the role mobile elements play in gene inactivations. Finally, we postulate the supply to the host of the essential riboflavin (vitamin B2) as key to the establishment of S. symbiotica as a co-obligate endosymbiont in the aphids belonging to the subfamily Lachninane. PMID:24951564

Diptera vectors of avian Haemosporidian parasites: untangling parasite life cycles and their taxonomy.

PubMed

Santiago-Alarcon, Diego; Palinauskas, Vaidas; Schaefer, Hinrich Martin

2012-11-01

Haemosporida is a large group of vector-borne intracellular parasites that infect amphibians, reptiles, birds, and mammals. This group includes the different malaria parasites (Plasmodium spp.) that infect humans around the world. Our knowledge on the full life cycle of these parasites is most complete for those parasites that infect humans and, to some extent, birds. However, our current knowledge on haemosporidian life cycles is characterized by a paucity of information concerning the vector species responsible for their transmission among vertebrates. Moreover, our taxonomic and systematic knowledge of haemosporidians is far from complete, in particular because of insufficient sampling in wild vertebrates and in tropical regions. Detailed experimental studies to identify avian haemosporidian vectors are uncommon, with only a few published during the last 25 years. As such, little knowledge has accumulated on haemosporidian life cycles during the last three decades, hindering progress in ecology, evolution, and systematic studies of these avian parasites. Nonetheless, recently developed molecular tools have facilitated advances in haemosporidian research. DNA can now be extracted from vectors' blood meals and the vertebrate host identified; if the blood meal is infected by haemosporidians, the parasite's genetic lineage can also be identified. While this molecular tool should help to identify putative vector species, detailed experimental studies on vector competence are still needed. Furthermore, molecular tools have helped to refine our knowledge on Haemosporida taxonomy and systematics. Herein we review studies conducted on Diptera vectors transmitting avian haemosporidians from the late 1800s to the present. We also review work on Haemosporida taxonomy and systematics since the first application of molecular techniques and provide recommendations and suggest future research directions. Because human encroachment on natural environments brings human

Impact of regulated secretion on anti-parasitic CD8 T cell responses

PubMed Central

Grover, Harshita Satija; Chu, H. Hamlet; Kelly, Felice D.; Yang, Soo Jung; Reese, Michael L.; Blanchard, Nicolas; Gonzalez, Federico; Chan, Shiao Wei; Boothroyd, John C.; Shastri, Nilabh; Robey, Ellen A.

2014-01-01

Summary CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen ROP5 that elicits a modest CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense granule antigen, GRA6, is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion impacts the efficacy of parasite-specific CD8 T cell responses. PMID:24857659

Extracellular functions of glycolytic enzymes of parasites: unpredicted use of ancient proteins.

PubMed

Gómez-Arreaza, Amaranta; Acosta, Hector; Quiñones, Wilfredo; Concepción, Juan Luis; Michels, Paul A M; Avilán, Luisana

2014-02-01

In addition of their usual intracellular localization where they are involved in catalyzing reactions of carbohydrate and energy metabolism by glycolysis, multiple studies have shown that glycolytic enzymes of many organisms, but notably pathogens, can also be present extracellularly. In the case of parasitic protists and helminths, they can be found either secreted or attached to the surface of the parasites. At these extracellular localizations, these enzymes have been shown to perform additional, very different so-called "moonlighting" functions, such as acting as ligands for a variety of components of the host. Due to this recognition, different extracellular glycolytic enzymes participate in various important parasite-host interactions such as adherence and invasion of parasites, modulation of the host's immune and haemostatic systems, promotion of angiogenesis, and acquisition of specific nutrients by the parasites. Accordingly, extracellular glycolytic enzymes are important for the invasion of the parasites and their establishment in the host, and in determining their virulence. Copyright © 2014 Elsevier B.V. All rights reserved.

Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum.

PubMed

Niemand, J; Louw, A I; Birkholtz, L; Kirk, K

2012-09-01

Polyamines and the enzymes involved in their biosynthesis are present at high levels in rapidly proliferating cells, including cancer cells and protozoan parasites. Inhibition of polyamine biosynthesis in asexual blood-stage malaria parasites causes cytostatic arrest of parasite development under in vitro conditions, but does not cure infections in vivo. This may be due to replenishment of the parasite's intracellular polyamine pool via salvage of exogenous polyamines from the host. However, the mechanism(s) of polyamine uptake by the intraerythrocytic parasite are not well understood. In this study, the uptake of the polyamines, putrescine and spermidine, into Plasmodium falciparum parasites functionally isolated from their host erythrocyte was investigated using radioisotope flux techniques. Both putrescine and spermidine were taken up into isolated parasites via a temperature-dependent process that showed cross-competition between different polyamines. There was also some inhibition of polyamine uptake by basic amino acids. Inhibition of polyamine biosynthesis led to an increase in the total amount of putrescine and spermidine taken up from the extracellular medium. The uptake of putrescine and spermidine by isolated parasites was independent of extracellular Na(+) but increased with increasing external pH. Uptake also showed a marked dependence on the parasite's membrane potential, decreasing with membrane depolarization and increasing with membrane hyperpolarization. The data are consistent with polyamines being taken up into the parasite via an electrogenic uptake process, energised by the parasite's inwardly negative membrane potential. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

The interactions of intracellular Protista and their host cells, with special reference to heterotrophic organisms.

PubMed

Bannister, L H

1979-04-11

Intracellular genera are found in all the major groups of Protista, but are particularly common among the dinoflagellates, trypanosomatid zooflagellates and suctorian ciliates; the Sporozoa are nearly all intracellular at some stage of their life, and the Microspora entirely so. Intracellular forms can dwell in the nucleus, within phagosomal or other vacuoles or may lie free in the hyaloplasm of their host cells. Organisms tend to select their hosts from a restricted taxonomic range although there are some notable exceptions. There is also great variation in the types of host cell inhabited. There are various reasons for both host and cell selectivity including recognition phenomena at the cell surfaces. Invasion of host cells is usually preceded by surface interactions with the invader. Some organisms depend upon phagocytosis for entry, but others induce host cells to engulf them by non-phagocytic means or invade by microinjection through the host plasma membrane. Protista avoid lysosomal destruction by their resistance to enzyme attack, by surrounding themselves with lysosome-inhibiting vacuoles, by escaping from the phagosomal system into the hyaloplasm and by choosing host cells which lack lysosomes. Nutrition of intracellular heterotrophic organisms involves some degree of competition with the host cell's metabolism as well as erosion of host cell cytoplasm. In Plasmodium infections, red cells are made more permeable to required nutrients by the action of the parasite on the host cell membrane. The parasite is often dependent upon the host cell for complex nutrients which it cannot synthesize for itself. Intracellular forms often profoundly modify the structure and metabolism of the host cell or interfere with its growth and multiplication. This may result in the final lysis of the host cell at the end of the intracellular phase or before the infection of other cells. Certain types of intracellular organisms may have arisen initially as forms attached to the

PLANT EVOLUTION. Convergent evolution of strigolactone perception enabled host detection in parasitic plants.

PubMed

Conn, Caitlin E; Bythell-Douglas, Rohan; Neumann, Drexel; Yoshida, Satoko; Whittington, Bryan; Westwood, James H; Shirasu, Ken; Bond, Charles S; Dyer, Kelly A; Nelson, David C

2015-07-31

Obligate parasitic plants in the Orobanchaceae germinate after sensing plant hormones, strigolactones, exuded from host roots. In Arabidopsis thaliana, the α/β-hydrolase D14 acts as a strigolactone receptor that controls shoot branching, whereas its ancestral paralog, KAI2, mediates karrikin-specific germination responses. We observed that KAI2, but not D14, is present at higher copy numbers in parasitic species than in nonparasitic relatives. KAI2 paralogs in parasites are distributed into three phylogenetic clades. The fastest-evolving clade, KAI2d, contains the majority of KAI2 paralogs. Homology models predict that the ligand-binding pockets of KAI2d resemble D14. KAI2d transgenes confer strigolactone-specific germination responses to Arabidopsis thaliana. Thus, the KAI2 paralogs D14 and KAI2d underwent convergent evolution of strigolactone recognition, respectively enabling developmental responses to strigolactones in angiosperms and host detection in parasites. Copyright © 2015, American Association for the Advancement of Science.

Killing of Leishmania parasites in activated murine macrophages is based on an L-arginine-dependent process that produces nitrogen derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maul, J.R.; Ransijn, A.; Buchmueller-Rouiller, Y.

1991-01-01

The experiments described in this report were aimed at determining whether L-arginine (L-arg)-derived nitrogen oxidation products (nitric oxide, nitrous acid, nitrites) are involved in the intracellular killing of Leishmania parasites by activated murine macrophages in vitro. Peritoneal or bone marrow-derived macrophages were infected with L. enriettii or L. major, then activated by exposure to recombinant murine interferon-gamma or to macrophage activating factor (MAF)-rich media in the presence of lipopolysaccharide. Activation of macrophages in regular (i.e., arginine-containing) culture medium led to complete destruction of the microorganisms within 24 h (L. enriettii) or 48 h (L. major), concomitant with accumulation of nitritesmore » (NO2-) in the culture fluids. When macrophage activation was carried out in L-arg-free medium, however, neither parasite killing nor NO2- production was obtained. A similar inhibition of macrophage leishmanicidal activity and of NO2- release was observed using media treated with arginase (which converts L-arg to urea and ornithine), or supplemented with NG-monomethyl-L-arg or guanidine (which inhibit the conversion of L-arg to nitrogen oxidation products). In all these situations, an excellent correlation between the levels of NO2- production by macrophages and intracellular killing of Leishmania was observed, whereas no strict correlation was detectable between leishmanicidal activity and superoxide production. Intracellular parasite killing by activated macrophages could be prevented by addition of iron salts to the incubation fluids. Incubation of free parasites with NaNO2 at acid pH led to immobilisation, multiplication arrest, and morphological degeneration of the microorganisms. Similarly, exposure of infected cells to NaNO2 led to killing of the intracellular parasite without affecting macrophage viability.« less

Deception and Manipulation: The Arms of Leishmania, a Successful Parasite

PubMed Central

Cecílio, Pedro; Pérez-Cabezas, Begoña; Santarém, Nuno; Maciel, Joana; Rodrigues, Vasco; Cordeiro da Silva, Anabela

2014-01-01

Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interactions between the parasite and the host immune system. Consequently, leishmaniasis can be manifested as a self-healing cutaneous affliction or a visceral pathology, being the last one fatal in 85–90% of untreated cases. As a result of a long host–parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection. Only through deception and manipulation of the immune system, Leishmania spp. can complete its life cycle and survive. The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches. Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system. PMID:25368612

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

PubMed Central

Bastidas, Robert J.

2016-01-01

SUMMARY Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. PMID:27030552

Detecting the elusive cost of parasites on fig seed production

NASA Astrophysics Data System (ADS)

Segar, Simon T.; Mardiastuti, Ani; Wheeler, Philip M.; Cook, James M.

2018-07-01

Mutualisms provide essential ecosystem functions such as pollination and contribute considerably to global biodiversity. However, they are also exploited by parasites that remove resources and thus impose costs on one or both of the mutualistic partners. The fig/pollinator interaction is a classic obligate mutualism; it is pantropical and involves >750 Ficus species and their host-specific pollinating wasps (family Agaonidae). Figs also host parasites of the mutualism that should consume pollinators or seeds, depending on their larval ecology. We collected data from a large crop of figs on Ficus glandifera var. brachysyce in a Sulawesi rainforest with an unusually high number of Eukoebelea sp. parasites. We found that these parasites have a significant negative correlation with fig seed production as well as with pollinator offspring production. Eukoebelea wasps form the basal genus in subfamily Sycophaginae (Chalcidoidea) and their larval biology is considered unknown. Our analysis suggests that they feed as flower gallers and impose direct costs on the fig tree, but a strategy including the consumption of pollinator larvae cannot be ruled out. We also present baseline data on the composition of the fig wasp community associated with F. glandifera var brachysyce and light trap catch data.

Methionine transport in the malaria parasite Plasmodium falciparum.

PubMed

Cobbold, Simon A; Martin, Rowena E; Kirk, Kiaran

2011-01-01

The intraerythrocytic malaria parasite, Plasmodium falciparum, derives amino acids from the digestion of host cell haemoglobin. However, it also takes up amino acids from the extracellular medium. Isoleucine is absent from adult human haemoglobin and an exogenous source of isoleucine is essential for parasite growth. An extracellular source of methionine is also important for the normal growth of at least some parasite strains. In this study we have characterised the uptake of methionine by P. falciparum-infected human erythrocytes, and by parasites functionally isolated from their host cells by saponin-permeabilization of the erythrocyte membrane. Infected erythrocytes take up methionine much faster than uninfected erythrocytes, with the increase attributable to the flux of this amino acid via the New Permeability Pathways induced by the parasite in the erythrocyte membrane. Having entered the infected cell, methionine is taken up by the intracellular parasite via a saturable, temperature-dependent process that is independent of ATP, Na(+) and H(+). Substrate competition studies, and comparison of the transport of methionine with that of isoleucine and leucine, yielded results consistent with the hypothesis that the parasite has at its surface one or more transporters which mediate the flux into and out of the parasite of a broad range of neutral amino acids. These transporters function most efficiently when exchanging one neutral amino acid for another, thus providing a mechanism whereby the parasite is able to import important exogenous amino acids in exchange for surplus neutral amino acids liberated from the digestion of host cell haemoglobin. Copyright © 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Susceptibility of promastigotes and intracellular amastigotes from distinct Leishmania species to the calpain inhibitor MDL28170.

PubMed

de Sousa Araújo, Pedro Soares; de Oliveira, Simone Santiago Carvalho; d'Avila-Levy, Claudia Masini; Dos Santos, André Luis Souza; Branquinha, Marta Helena

2018-05-04

Despite the available drug options, leishmaniasis treatment remains unsatisfactory. The repurposing of calpain inhibitors originally developed for human diseases became an interesting alternative, since Leishmania cells express calpain-related proteins. The susceptibility of six Leishmania species (L. amazonensis, L. braziliensis, L. major, L. mexicana, L. chagasi, and L. donovani) to the calpain inhibitor MDL28170 was determined. Promastigote and intracellular amastigote viability in the presence of MDL28170 was evaluated. MDL28170 was able to reduce promastigote proliferation in a dose-dependent manner for all the parasites. A significant reduction on the general parasite metabolism was detected, as judged by resazurin assay, as well as induced important morphological alterations, including rounding promastigotes and loss of the flagellum. MDL28170 was also able to reduce the number of intracellular amastigotes in RAW macrophages. The susceptibility of both parasite stages (promastigotes and amastigotes) to MDL28170 was similar for all Leishmania species tested. MDL28170 showed a much higher toxicity to Leishmania amastigotes when compared with mammalian macrophages, displaying selectivity index values varying from 13.1 to 39.8. These results suggest that the development of calpain inhibitors may represent an interesting alternative in the treatment of leishmaniasis.

Passive transfer of leishmania lipopolysaccharide confers parasite survival in macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Handman, E.; Schnur, L.F.; Spithill, T.W.

1986-12-01

Infection of macrophages by the intracellular protozoan parasite Leishmania involves specific attachment to the host membrane, followed by phagocytosis and intracellular survival and growth. Two parasite molecules have been implicated in the attachment event: Leishmania lipopolysaccharide (L-LPS) and a glycoprotein (gp63). This study was designed to clarify the role of L-LPS in infection and the stage in the process of infection at which it operates. The authors have recently identified a Leishmania major strain (LRC-L119) which lacks the L-LPS molecule and is not infective for hamsters or mice. This parasite was isolated from a gerbil in Kenya and was identifiedmore » phenotypically as L. major by isoenzyme and fatty acid analysis. In this study they have confirmed at the genotype level that LRC-L119 is L. major by analyzing and comparing the organization of cloned DNA sequences in the genome of different strains of L. major. Here they show that LRC-L119 promastigotes are phagocytosed rapidly by macrophages in vitro, but in contrast to virulent strains of L. major, they are then killed over a period of 18 hr. In addition, they show that transfer of purified L-LPS from a virulent clone of L. major (V121) into LRC-L119 promastigotes confers on them the ability to survive in macrophages in vitro.« less

Shared neural substrates for song discrimination in parental and parasitic songbirds.

PubMed

Louder, Matthew I M; Voss, Henning U; Manna, Thomas J; Carryl, Sophia S; London, Sarah E; Balakrishnan, Christopher N; Hauber, Mark E

2016-05-27

In many social animals, early exposure to conspecific stimuli is critical for the development of accurate species recognition. Obligate brood parasitic songbirds, however, forego parental care and young are raised by heterospecific hosts in the absence of conspecific stimuli. Having evolved from non-parasitic, parental ancestors, how brood parasites recognize their own species remains unclear. In parental songbirds (e.g. zebra finch Taeniopygia guttata), the primary and secondary auditory forebrain areas are known to be critical in the differential processing of conspecific vs. heterospecific songs. Here we demonstrate that the same auditory brain regions underlie song discrimination in adult brood parasitic pin-tailed whydahs (Vidua macroura), a close relative of the zebra finch lineage. Similar to zebra finches, whydahs showed stronger behavioral responses during conspecific vs. heterospecific song and tone pips as well as increased neural responses within the auditory forebrain, as measured by both functional magnetic resonance imaging (fMRI) and immediate early gene (IEG) expression. Given parallel behavioral and neuroanatomical patterns of song discrimination, our results suggest that the evolutionary transition to brood parasitism from parental songbirds likely involved an "evolutionary tinkering" of existing proximate mechanisms, rather than the wholesale reworking of the neural substrates of species recognition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Survey and analysis of major human parasitic diseases in Chongqing City].

PubMed

Shan-Shan, Li; Fei, Luo; Jun, Xie; Yi, Yuan

2018-03-02

To investigate the epidemic of major human parasitic diseases in Chongqing City, so as to provide a reference for developing prevention and control strategies. According to the unified methods formulated by the national investigation scheme and stratified cluster random sampling, 36 rural pilots and 50 urban pilots were selected in Chongqing City. The number of the objects investigated in individual pilot was defined over 250. Totally 22 263 residents were detected. The overall infection rate of intestinal parasites was 5.41%. The infection rates of Ascaris lumbricoides , hookworm, Trichuris trichiura , and Enterobius vermicularis were 1.20%, 4.23%, 0.13% and 0.47% respectively. Only 0.22% of the infections were co-infections. The infection rate of overall intestinal parasites was statistically higher in the females than that in the males ( χ 2 = 15.19, P < 0.05), and the infection rates were significantly different among various age groups, occupations, education levels, and regions ( χ 2 = 15.19, 396.72, 421.07, 347.79, all P < 0.05). The infection rates of major human parasites in Chongqing show an obviously decreasing tendency compared with the rates of the past twice of national surveys. In the future, the controlling practices are obliged to focus on reducing the infection rates of soil-borne parasites.

A Sense of Obligation: Cultural Differences in the Experience of Obligation.

PubMed

Buchtel, Emma E; Ng, Leo C Y; Norenzayan, Ara; Heine, Steven J; Biesanz, Jeremy C; Chen, Sylvia Xiaohua; Bond, Michael Harris; Peng, Qin; Su, Yanjie

2018-05-01

In this investigation of cultural differences in the experience of obligation, we distinguish between Confucian Role Ethics versus Relative Autonomy lay theories of motivation and illustrate them with data showing relevant cultural differences in both social judgments and intrapersonal experience. First, when judging others, Western European heritage culture (WEHC) participants (relative to Confucian heritage culture [CHC] participants) judged obligation-motivated actors more negatively than those motivated by agency (Study 1, N = 529). Second, in daily diary and situation sampling studies, CHC participants (relative to WEHC participants) perceived more congruency between their own agentic and obligated motivations, and more positive emotional associations with obligated motivations (Study 2, N = 200 and Study 3, N = 244). Agentic motivation, however, was universally associated with positive emotions. More research on a Role Ethics rather than Relative Autonomy conception of agency may improve our understanding of human motivation, especially across cultures.

Identification, biochemical characterization, and in-vivo expression of the intracellular invertase BfrA from the pathogenic parasite Leishmania major.

PubMed

Belaz, Sorya; Rattier, Thibault; Lafite, Pierre; Moreau, Philippe; Routier, Françoise H; Robert-Gangneux, Florence; Gangneux, Jean-Pierre; Daniellou, Richard

2015-10-13

The parasitic life cycle of Leishmania includes an extracellular promastigote stage that occurs in the gut of the insect vector. During that period, the sucrose metabolism and more specifically the first glycosidase of this pathway are essential for growth and survival of the parasite. We investigated the expression of the invertase BfrA in the promastigote and amastigote stages of three parasite species representative of the three various clinical forms and of various geographical areas, namely Leishmania major, L. donovani and L. braziliensis. Thereafter, we cloned, overexpressed and biochemically characterized this invertase BfrA from L. major, heterologously expressed in both Escherichia coli and L. tarentolae. For all species, expression levels of BfrA mRNA were correlated to the time of the culture and the parasitic stage (promastigotes > amastigotes). BfrA exhibited no activity when expressed as a glycoprotein in L. tarentolae but proved to be an invertase when not glycosylated, yet owing low sequence homology with other invertases from the same family. Our data suggest that BfrA is an original invertase that is located inside the parasite. It is expressed in both parasitic stages, though to a higher extent in promastigotes. This work provides new insight into the parasite sucrose metabolism. Copyright © 2015 Elsevier Ltd. All rights reserved.

"Obligated aliens": recognizing sperm donors' ethical obligation to disclose genetic information.

PubMed

Tamir, Sivan

2013-03-01

Sperm donors' obligations are typically constrained to the immediate circumstances surrounding the donation and to its time frame. This paper makes the case for recognizing an ongoing ethical obligation that binds sperm donors to disclose, in a timely manner, meaningful genetic information to recipients and donor-conceived children. The paper delineates and conceptualizes the suggested (potentially reciprocal) duty and argues that it is not the genetic link between the donor and the donor-conceived child that binds donors by said duty, but rather social responsibility. Accordingly, an original perception of the donor as an obligated alien is suggested and developed. The main thesis of the paper is supported inter alia by a comparison between transmitting infectious diseases and passing faulty genes on to donor-conceived children. The paper also provides an in-depth analysis of the conflicting interests of the parties generated by such an obligation and proposes a model for embedding this ethical duty in a (legal) contractual framework.

Involvement of Apoptosis in Host-Parasite Interactions in the Zebra Mussel

PubMed Central

Minguez, Laëtitia; Brulé, Nelly; Sohm, Bénédicte; Devin, Simon; Giambérini, Laure

2013-01-01

The question of whether cell death by apoptosis plays a biological function during infection is key to understanding host-parasite interactions. We investigated the involvement of apoptosis in several host-parasite systems, using zebra mussels Dreissena polymorpha as test organisms and their micro- and macroparasites. As a stress response associated with parasitism, heat shock proteins (Hsp) can be induced. In this protein family, Hsp70 are known to be apoptosis inhibitors. Mussels were diagnosed for their respective infections by standard histological methods; apoptosis was detected using the TUNEL methods on paraffin sections and Hsp70 by immunohistochemistry on cryosections. Circulating hemocytes were the main cells observed in apoptosis whereas infected tissues displayed no or few apoptotic cells. Parasitism by intracellular bacteria Rickettsiales-like and the trematode Bucephalus polymorphus were associated with the inhibition of apoptosis whereas ciliates Ophryoglena spp. or the trematode Phyllodistomum folium did not involve significant differences in apoptosis. Even if some parasites were able to modulate apoptosis in zebra mussels, we did not see evidence of any involvement of Hsp70 on this mechanism. PMID:23785455

Toxoplasma gondii F-actin forms an extensive filamentous network required for material exchange and parasite maturation

PubMed Central

Periz, Javier; Whitelaw, Jamie; Harding, Clare; Gras, Simon; Del Rosario Minina, Mario Igor; Latorre-Barragan, Fernanda; Lemgruber, Leandro; Reimer, Madita Alice; Insall, Robert; Heaslip, Aoife; Meissner, Markus

2017-01-01

Apicomplexan actin is important during the parasite's life cycle. Its polymerization kinetics are unusual, permitting only short, unstable F-actin filaments. It has not been possible to study actin in vivo and so its physiological roles have remained obscure, leading to models distinct from conventional actin behaviour. Here a modified version of the commercially available actin-chromobody was tested as a novel tool for visualising F-actin dynamics in Toxoplasma gondii. Cb labels filamentous actin structures within the parasite cytosol and labels an extensive F-actin network that connects parasites within the parasitophorous vacuole and allows vesicles to be exchanged between parasites. In the absence of actin, parasites lack a residual body and inter-parasite connections and grow in an asynchronous and disorganized manner. Collectively, these data identify new roles for actin in the intracellular phase of the parasites lytic cycle and provide a robust new tool for imaging parasitic F-actin dynamics. DOI: http://dx.doi.org/10.7554/eLife.24119.001 PMID:28322189

Toxoplasma gondii F-actin forms an extensive filamentous network required for material exchange and parasite maturation.

PubMed

Periz, Javier; Whitelaw, Jamie; Harding, Clare; Gras, Simon; Del Rosario Minina, Mario Igor; Latorre-Barragan, Fernanda; Lemgruber, Leandro; Reimer, Madita Alice; Insall, Robert; Heaslip, Aoife; Meissner, Markus

2017-03-21

Apicomplexan actin is important during the parasite's life cycle. Its polymerization kinetics are unusual, permitting only short, unstable F-actin filaments. It has not been possible to study actin in vivo and so its physiological roles have remained obscure, leading to models distinct from conventional actin behaviour. Here a modified version of the commercially available actin-chromobody was tested as a novel tool for visualising F-actin dynamics in Toxoplasma gondii. Cb labels filamentous actin structures within the parasite cytosol and labels an extensive F-actin network that connects parasites within the parasitophorous vacuole and allows vesicles to be exchanged between parasites. In the absence of actin, parasites lack a residual body and inter-parasite connections and grow in an asynchronous and disorganized manner. Collectively, these data identify new roles for actin in the intracellular phase of the parasites lytic cycle and provide a robust new tool for imaging parasitic F-actin dynamics.

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen.

PubMed

Bastidas, Robert J; Valdivia, Raphael H

2016-06-01

Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Chick loss from mixed broods reflects severe nestmate competition between an evictor brood parasite and its hosts.

PubMed

Moskát, Csaba; Hauber, Márk E

2010-03-01

Hatchlings of the obligate brood parasite common cuckoo Cuculus canorus typically evict eggs and nestmates but, rarely, host and parasite nestlings may grow up together. As part of previous experiments, we manipulated host clutches by inducing two great reed warbler Acrocephalus arundinaceus and one parasite young to share a nest from 4 days posthatch, when the cuckoo's eviction behaviour is thought to cease. We documented that in mixed broods typically at least one nestling eventually fell out of nest during the period of 5-10 days posthatch. In 83% of nests one or two host chicks disappeared, and in 17% of nests parasite chicks were lost. All nestlings remained in control broods of three hosts or one parasite. These results imply strong physical competition for space in mixed broods. We suggest that continued foster care for parasitized broods may occasionally be beneficial because host nestlings have some chance to escape the costs of parasitism, even when their parents fail to reject the parasite's egg and the parasite hatchling fails to evict nestmates. Conversely, evictor parasite chicks benefit not only through improved growth, as reported before, but also through the elimination of nestmate competition for space and the risk of displacement from mixed broods. Copyright (c) 2010 Elsevier B.V. All rights reserved.

The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery

PubMed Central

Späth, Gerald F.; Rachidi, Najma; Prina, Eric

2017-01-01

The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival. PMID:28594938

MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs.

PubMed

Shahid, Saima; Kim, Gunjune; Johnson, Nathan R; Wafula, Eric; Wang, Feng; Coruh, Ceyda; Bernal-Galeano, Vivian; Phifer, Tamia; dePamphilis, Claude W; Westwood, James H; Axtell, Michael J

2018-01-03

Dodders (Cuscuta spp.) are obligate parasitic plants that obtain water and nutrients from the stems of host plants via specialized feeding structures called haustoria. Dodder haustoria facilitate bidirectional movement of viruses, proteins and mRNAs between host and parasite, but the functional effects of these movements are not known. Here we show that Cuscuta campestris haustoria accumulate high levels of many novel microRNAs (miRNAs) while parasitizing Arabidopsis thaliana. Many of these miRNAs are 22 nucleotides in length. Plant miRNAs of this length are uncommon, and are associated with amplification of target silencing through secondary short interfering RNA (siRNA) production. Several A. thaliana mRNAs are targeted by 22-nucleotide C. campestris miRNAs during parasitism, resulting in mRNA cleavage, secondary siRNA production, and decreased mRNA accumulation. Hosts with mutations in two of the loci that encode target mRNAs supported significantly higher growth of C. campestris. The same miRNAs that are expressed and active when C. campestris parasitizes A. thaliana are also expressed and active when it infects Nicotiana benthamiana. Homologues of target mRNAs from many other plant species also contain the predicted target sites for the induced C. campestris miRNAs. These data show that C. campestris miRNAs act as trans-species regulators of host-gene expression, and suggest that they may act as virulence factors during parasitism.

Endangered light-footed clapper rail affects parasite community structure in coastal wetlands

USGS Publications Warehouse

Whitney, Kathleen L.; Hechinger, Ryan F.; Kuris, Armand M.; Lafferty, Kevin D.

2007-01-01

An extinction necessarily affects community members that have obligate relationships with the extinct species. Indirect or cascading effects can lead to even broader changes at the community or ecosystem level. However, it is not clear whether generalist parasites should be affected by the extinction of one of their hosts. We tested the prediction that loss of a host species could affect the structure of a generalist parasite community by investigating the role of endangered Light-footed Clapper Rails (Rallus longirostris levipes) in structuring trematode communities in four tidal wetlands in southern California, USA (Carpinteria Salt Marsh, Mugu Lagoon) and Mexico (Estero de Punta Banda, Bahia Falsa–San Quintín). We used larval trematode parasites in first intermediate host snails (Cerithidea californica) as windows into the adult trematodes that parasitize Clapper Rails. Within and among wetlands, we found positive associations between Clapper Rails and four trematode species, particularly in the vegetated marsh habitat where Clapper Rails typically occur. This suggests that further loss of Clapper Rails is likely to affect the abundance of several competitively dominant trematode species in wetlands with California horn snails, with possible indirect effects on the trematode community and changes in the impacts of these parasites on fishes and invertebrates.

[Book review] Cowbirds and Other Brood Parasites by Catherine Ortega. Tucson, Arizona: University of Arizona Press (1998). The Avian Brood Parasites: Deception at the Nest by Paul A. Johnsgard. New York: Oxford University Press (1997) Parasitic Birds and their Hosts: Studies in Coevolution edited by S.I. Rothstein & S.K. Robinson. New York: Oxford University Press (1998)

USGS Publications Warehouse

Hahn, D.C.

1999-01-01

We are in a golden age for the study of brood parasitism, judging from both the quantity and quality of recent scientific publications on cuckoos, cowbirds and parasitic finches by investigators working in Europe, the Americas, Africa and Asia. As Johnsgard (1997) remarks in his preface, the evolutionary, ecological, and behavioural questions posed by obligate brood parasites are among the most intriguing contemporary ornithological topics. Rothstein & Robinson (1998) explain that brood parasites make ideal subjects for testing the generality of models for the evolution of social and mating behaviour, foraging behaviour, spatial distribution, and vocal development, because the strategy of providing no parental care removes constraints imposed on other birds. Since Aristotle, people have been fascinated by brood parasites, but only in the past two decades has the number of investigators working on this topic reached a critical mass and created momentum that promises many breakthroughs. New studies are being completed so rapidly that a general book is inevitably out of date on some topics by the time it is published. A complete library on brood parasitism should add two recent volumes (Morrison et al. 1999; Smith et al., in press).to the three reviewed here.

Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites

PubMed Central

Gordon, Jennifer L; Sibley, L David

2005-01-01

Background The phylum Apicomplexa is an early-branching eukaryotic lineage that contains a number of important human and animal pathogens. Their complex life cycles and unique cytoskeletal features distinguish them from other model eukaryotes. Apicomplexans rely on actin-based motility for cell invasion, yet the regulation of this system remains largely unknown. Consequently, we focused our efforts on identifying actin-related proteins in the recently completed genomes of Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., and Theileria spp. Results Comparative genomic and phylogenetic studies of apicomplexan genomes reveals that most contain only a single conventional actin and yet they each have 8–10 additional actin-related proteins. Among these are a highly conserved Arp1 protein (likely part of a conserved dynactin complex), and Arp4 and Arp6 homologues (subunits of the chromatin-remodeling machinery). In contrast, apicomplexans lack canonical Arp2 or Arp3 proteins, suggesting they lost the Arp2/3 actin polymerization complex on their evolutionary path towards intracellular parasitism. Seven of these actin-like proteins (ALPs) are novel to apicomplexans. They show no phylogenetic associations to the known Arp groups and likely serve functions specific to this important group of intracellular parasites. Conclusion The large diversity of actin-like proteins in apicomplexans suggests that the actin protein family has diverged to fulfill various roles in the unique biology of intracellular parasites. Conserved Arps likely participate in vesicular transport and gene expression, while apicomplexan-specific ALPs may control unique biological traits such as actin-based gliding motility. PMID:16343347

Conventional oil and natural gas infrastructure increases brown-headed cowbird (Molothrus ater) relative abundance and parasitism in mixed-grass prairie.

PubMed

Bernath-Plaisted, Jacy; Nenninger, Heather; Koper, Nicola

2017-07-01

The rapid expansion of oil and natural gas development across the Northern Great Plains has contributed to habitat fragmentation, which may facilitate brood parasitism of ground-nesting grassland songbird nests by brown-headed cowbirds ( Molothrus ater ), an obligate brood parasite, through the introduction of perches and anthropogenic edges. We tested this hypothesis by measuring brown-headed cowbird relative abundance and brood parasitism rates of Savannah sparrow ( Passerculus sandwichensis ) nests in relation to the presence of infrastructure features and proximity to potential perches and edge habitat. The presence of oil and natural gas infrastructure increased brown-headed cowbird relative abundance by a magnitude of four times, which resulted in four times greater brood parasitism rates at infrastructure sites. While the presence of infrastructure and the proximity to roads were influential in predicting brood parasitism rates, the proximity of perch sites was not. This suggests that brood parasitism associated with oil and natural gas infrastructure may result in additional pressures that reduce productivity of this declining grassland songbird.

Parasites and phytoplankton, with special emphasis on dinoflagellate infections.

PubMed

Park, Myung Gil; Yih, Wonho; Coats, D Wayne

2004-01-01

Planktonic members of most algal groups are known to harbor intracellular symbionts, including viruses, bacteria, fungi, and protozoa. Among the dinoflagellates, viral and bacterial associations were recognized a quarter century ago, yet their impact on host populations remains largely unresolved. By contrast, fungal and protozoan infections of dinoflagellates are well documented and generally viewed as playing major roles in host population dynamics. Our understanding of fungal parasites is largely based on studies for freshwater diatoms and dinoflagellates, although fungal infections are known for some marine phytoplankton. In freshwater systems, fungal chytrids have been linked to mass mortalities of host organisms, suppression or retardation of phytoplankton blooms, and selective effects on species composition leading to successional changes in plankton communities. Parasitic dinoflagellates of the genus Amoebophrya and the newly described Perkinsozoa, Parvilucifera infectans, are widely distributed in coastal waters of the world where they commonly infect photosynthetic and heterotrophic dinoflagellates. Recent work indicates that these parasites can have significant impacts on host physiology, behavior, and bloom dynamics. Thus, parasitism needs to be carefully considered in developing concepts about plankton dynamics and the flow of material in marine food webs.

Unique physiology of host-parasite interactions in microsporidia infections.

PubMed

Williams, Bryony A P

2009-11-01

Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.

Msp40 effector of root-knot nematode manipulates plant immunity to facilitate parasitism.

PubMed

Niu, Junhai; Liu, Pei; Liu, Qian; Chen, Changlong; Guo, Quanxin; Yin, Junmei; Yang, Guangsui; Jian, Heng

2016-01-22

Root-knot nematodes (RKNs) are obligate biotrophic parasites that invade plant roots and engage in prolonged and intimate relationships with their hosts. Nematode secretions, some of which have immunosuppressing activity, play essential roles in successful parasitism; however, their mechanisms of action remain largely unknown. Here, we show that the RKN-specific gene MiMsp40, cloned from Meloidogyne incognita, is expressed exclusively in subventral oesophageal gland cells and is strongly upregulated during early parasitic stages. Arabidopsis plants overexpressing MiMsp40 were more susceptible to nematode infection than were wild type plants. Conversely, the host-derived MiMsp40 RNAi suppressed nematode parasitism and/or reproduction. Moreover, overexpression of MiMsp40 in plants suppressed the deposition of callose and the expression of marker genes for bacterial elicitor elf18-triggered immunity. Transient expression of MiMsp40 prevented Bax-triggered defence-related programmed cell death. Co-agroinfiltration assays indicated that MiMsp40 also suppressed macroscopic cell death triggered by MAPK cascades or by the ETI cognate elicitors R3a/Avr3a. Together, these results demonstrate that MiMsp40 is a novel Meloidogyne-specific effector that is injected into plant cells by early parasitic stages of the nematode and that plays a role in suppressing PTI and/or ETI signals to facilitate RKN parasitism.

Msp40 effector of root-knot nematode manipulates plant immunity to facilitate parasitism

PubMed Central

Niu, Junhai; Liu, Pei; Liu, Qian; Chen, Changlong; Guo, Quanxin; Yin, Junmei; Yang, Guangsui; Jian, Heng

2016-01-01

Root-knot nematodes (RKNs) are obligate biotrophic parasites that invade plant roots and engage in prolonged and intimate relationships with their hosts. Nematode secretions, some of which have immunosuppressing activity, play essential roles in successful parasitism; however, their mechanisms of action remain largely unknown. Here, we show that the RKN-specific gene MiMsp40, cloned from Meloidogyne incognita, is expressed exclusively in subventral oesophageal gland cells and is strongly upregulated during early parasitic stages. Arabidopsis plants overexpressing MiMsp40 were more susceptible to nematode infection than were wild type plants. Conversely, the host-derived MiMsp40 RNAi suppressed nematode parasitism and/or reproduction. Moreover, overexpression of MiMsp40 in plants suppressed the deposition of callose and the expression of marker genes for bacterial elicitor elf18-triggered immunity. Transient expression of MiMsp40 prevented Bax-triggered defence-related programmed cell death. Co-agroinfiltration assays indicated that MiMsp40 also suppressed macroscopic cell death triggered by MAPK cascades or by the ETI cognate elicitors R3a/Avr3a. Together, these results demonstrate that MiMsp40 is a novel Meloidogyne-specific effector that is injected into plant cells by early parasitic stages of the nematode and that plays a role in suppressing PTI and/or ETI signals to facilitate RKN parasitism. PMID:26797310

In vitro activity of the beta-carboline alkaloids harmane, harmine, and harmaline toward parasites of the species Leishmania infantum.

PubMed

Di Giorgio, C; Delmas, F; Ollivier, E; Elias, R; Balansard, G; Timon-David, P

2004-01-01

Harmane, harmine, and harmaline were investigated for their in vitro antileishmanial activity toward parasites of the species Leishmania infantum. Harmane and Harmine displayed a moderate antiproliferative activity toward human monocytes and exerted a weak antileishmanial activity toward both the promastigote and the amastigote forms of the parasite. Their mechanism of action on the promastigote form of the parasite involved interactions with DNA metabolism leading to an accumulation of parasites in the S-G(2)M phases of the cell-cycle. Harmaline, at the contrary, was deprived from toxicity toward human cells and Leishmania promastigotes, however it exerted a strong antileishmanial activity toward the intracellular amastigote form of the parasite. This property was shown to partly result from the capacity of the molecule to prevent parasite internalization within macrophages by inhibiting Leishmania PKC activity.

The consequences of the intracellular retention of pathogen-derived T-cell-independent antigens on protein presentation to T cells.

PubMed

Leyva-Cobián, F; Outschoorn, I M; Carrasco-Marín, E; Alvarez-Domínguez, C

1997-10-01

Intracellular pathogens can be considered as particulate antigens chemically composed of a complex mixture of T-cell-dependent antigens (TD) (peptides and proteins) and T-cell-independent antigens (TI) (glycolipids and complex polysaccharides). A large range of saccharides (from oligosaccharides to complex polysaccharides) derived from pathogenic microorganisms are being isolated and characterized. They are currently implicated in signaling systems and concomitant host-parasite relationships. However, there are not many structure-function relationships described for these pathogens. This is particularly true of polysaccharides. In this report we have reviewed the role of defined TI antigens in the processing and presentation of defined TD antigens to specific T cells by antigen-presenting cells (APC). We also considered the importance of some of the chemical characteristics shared by different carbohydrates implicated in the inhibition of antigen presentation. These findings are discussed in relation to the clear immunopathological consequences of long retention periods of complex carbohydrate molecules derived from intracellular parasites inside certain APC and the absence of antigen presentation impairment in physiological situations such as the removal of senescent or damaged red blood cells by splenic macrophages or intracellular accumulation of carbohydrates in colostrum and milk macrophages during lactation.

Valosin-containing protein VCP/p97 is essential for the intracellular development of Leishmania and its survival under heat stress.

PubMed

Guedes Aguiar, Bruno; Padmanabhan, Prasad K; Dumas, Carole; Papadopoulou, Barbara

2018-06-12

Valosin-containing protein (VCP)/p97/Cdc48 is one of the best-characterised type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homologue (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, Leishmania infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive (ts) LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity. Interestingly, these VCP mutants are also unable to survive heat stress, and a ts VCP mutant is defective in amastigote growth. Consistent with LiVCP's essential function in amastigotes, LiVCP messenger ribonucleic acid undergoes 3'Untranslated Region (UTR)-mediated developmental regulation, resulting in higher VCP expression in amastigotes. Furthermore, we show that parasite mutant lines expressing lower VCP levels or dominant negative VCP forms exhibit high accumulation of polyubiquitinated proteins and increased sensitivity to proteotoxic stress, supporting the ubiquitin-selective chaperone function of LiVCP. Together, these results emphasise the crucial role LiVCP plays under heat stress and during the parasite intracellular development. © 2018 John Wiley & Sons Ltd.

Lay obligations in professional relations.

PubMed

Benjamin, M

1985-02-01

Little has been written recently about the obligations of lay people in professional relationships. Yet the Code of Medical Ethics adopted by the American Medical Association in 1847 included an extensive statement on "Obligations of patients to their physicians'. After critically examining the philosophical foundations of this statement, I provide an alternative account of lay obligations in professional relationships. Based on a hypothetical social contract and included in a full specification of professional as well as lay obligations, this account requires lay people to honor commitments and disclose relevant information. Ethically, the account assumes that all parties in lay-professional relationships should be given equal consideration and respect in determining rights and obligations. Factually, it assumes that the treatment of many illnesses and injuries required collaboration and cooperation among lay persons and health professionals, that medical resources and personnel are limited, and that medicine, nursing, and related health professions, are, in MacIntyre's sense, practices.

Developing an Apicomplexan DNA Barcoding System to Detect Blood Parasites of Small Coral Reef Fishes.

PubMed

Renoux, Lance P; Dolan, Maureen C; Cook, Courtney A; Smit, Nico J; Sikkel, Paul C

2017-08-01

Apicomplexan parasites are obligate parasites of many species of vertebrates. To date, there is very limited understanding of these parasites in the most-diverse group of vertebrates, actinopterygian fishes. While DNA barcoding targeting the eukaryotic 18S small subunit rRNA gene sequence has been useful in identifying apicomplexans in tetrapods, identification of apicomplexans infecting fishes has relied solely on morphological identification by microscopy. In this study, a DNA barcoding method was developed that targets the 18S rRNA gene primers for identifying apicomplexans parasitizing certain actinopterygian fishes. A lead primer set was selected showing no cross-reactivity to the overwhelming abundant host DNA and successfully confirmed 37 of the 41 (90.2%) microscopically verified parasitized fish blood samples analyzed in this study. Furthermore, this DNA barcoding method identified 4 additional samples that screened negative for parasitemia, suggesting this molecular method may provide improved sensitivity over morphological characterization by microscopy. In addition, this PCR screening method for fish apicomplexans, using Whatman FTA preserved DNA, was tested in efforts leading to a more simplified field collection, transport, and sample storage method as well as a streamlining sample processing important for DNA barcoding of large sample sets.

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMARON2 pair

USDA-ARS?s Scientific Manuscript database

Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the...

Context-specific parasitism in Tubifex tubifex in geothermally influenced stream reaches in Yellowstone National Park

USGS Publications Warehouse

Alexander, Julie D.; Kerans, Billie L.; Koel, Todd M.; Rasmussen, Charlotte

2011-01-01

Parasites can regulate host abundance and influence the composition and structure of communities. However, host-parasite interactions might be context-specific if environmental conditions can alter the outcome of parasitism and disease. An understanding of how host-parasite interactions might change in different contexts will be useful for predicting and managing disease against a background of anthropogenic environmental change. We examined the ecology of Myxobolus cerebralis, the parasite that causes whirling disease in salmonids, and its obligate host, Tubifex tubifex, in geothermally variable stream reaches in Yellowstone National Park. We identified reaches in 4 categories of geothermal influence, which were characterized by variable substrates, temperatures, specific conductivities, and pH. In each reach, we measured aspects of host ecology (abundance, relative abundance, size, and genotype of T. tubifex), parasite ecology (infection prevalence in T. tubifex and abundance of M. cerebralis-infected T. tubifex), and risk to fish of contracting whirling disease. Tubifex tubifex abundance was high all in reaches characterized by geothermal influence, whereas abundance of M. cerebralis-infected T. tubifex was high only in reaches characterized by intermediate geothermal influence. We suggest that habitat had a contextual effect on parasitism in the oligochaete host. Abundance of infected hosts appeared to depend on host abundance in all reach types except those with high geothermal influence, where abundance of infected hosts depended on environmental factors.

Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS.

PubMed

Dohmen, Luuk C T; Navas, Adriana; Vargas, Deninson Alejandro; Gregory, David J; Kip, Anke; Dorlo, Thomas P C; Gomez, Maria Adelaida

2016-04-29

Within its mammalian host, Leishmania resides and replicates as an intracellular parasite. The direct activity of antileishmanials must therefore depend on intracellular drug transport, metabolism, and accumulation within the host cell. In this study, we explored the role of human macrophage transporters in the intracellular accumulation and antileishmanial activity of miltefosine (MLF), the only oral drug available for the treatment of visceral and cutaneous leishmaniasis (CL). Membrane transporter gene expression in primary human macrophages infected in vitro with Leishmania Viannia panamensis and exposed to MLF showed modulation of ABC and solute liquid carrier transporters gene transcripts. Among these, ABCA3, a lipid transporter, was significantly induced after exposure to MLF, and this induction was confirmed in primary macrophages from CL patients. Functional validation of MLF as a substrate for ABCA3 was performed by shRNA gene knockdown (KD) in THP-1 monocytes. Intracellular accumulation of radiolabeled MLF was significantly higher in ABCA3(KD) macrophages. ABCA3(KD) resulted in increased cytotoxicity induced by MLF exposure. ABCA3 gene expression inversely correlated with intracellular MLF content in primary macrophages from CL patients. ABCA3(KD) reduced parasite survival during macrophage infection with an L. V. panamensis strain exhibiting low in vitro susceptibility to MLF. Confocal microscopy showed ABCA3 to be located in the cell membrane of resting macrophages and in intracellular compartments in L. V. panamensis-infected cells. These results provide evidence of ABCA3 as an MLF efflux transporter in human macrophages and support its role in the direct antileishmanial effect of this alkylphosphocholine drug. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Epidemiology of and Diagnostic Strategies for Toxoplasmosis

PubMed Central

Dardé, Marie-Laure

2012-01-01

Summary: The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last 40 years. This obligate intracellular parasite was identified early as a pathogen responsible for congenital infection, but its clinical expression and the importance of reactivations of infections in immunocompromised patients were recognized later, in the era of organ transplantation and HIV infection. Recent knowledge of host cell-parasite interactions and of parasite virulence has brought new insights into the comprehension of the pathophysiology of infection. In this review, we focus on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes. In particular, we provide critical information on diagnostic methods according to the patient's background and discuss the implementation of screening tools for congenital toxoplasmosis according to health policies. PMID:22491772

47 CFR 7.5 - General Obligations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

47 CFR 7.5 - General Obligations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

47 CFR 7.5 - General Obligations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

47 CFR 7.5 - General Obligations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

47 CFR 7.5 - General Obligations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false General Obligations. 7.5 Section 7.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Obligations-What Must Covered Entities Do? § 7.5 General Obligations...

Aminopeptidase N1 (EtAPN1), an M1 Metalloprotease of the Apicomplexan Parasite Eimeria tenella, Participates in Parasite Development

PubMed Central

Gras, Simon; Byzia, Anna; Gilbert, Florence B.; McGowan, Sheena; Drag, Marcin; Niepceron, Alisson; Lecaille, Fabien; Lalmanach, Gilles; Brossier, Fabien

2014-01-01

Aminopeptidases N are metalloproteases of the M1 family that have been reported in numerous apicomplexan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, and Eimeria. While investigating the potency of aminopeptidases as therapeutic targets against coccidiosis, one of the most important avian diseases caused by the genus Eimeria, we identified and characterized Eimeria tenella aminopeptidase N1 (EtAPN1). Its inhibition by bestatin and amastatin, as well as its reactivation by divalent ions, is typical of zinc-dependent metalloproteases. EtAPN1 shared a similar sequence, three-dimensional structure, and substrate specificity and similar kinetic parameters with A-M1 from Plasmodium falciparum (PfA-M1), a validated target in the treatment of malaria. EtAPN1 is synthesized as a 120-kDa precursor and cleaved into 96-, 68-, and 38-kDa forms during sporulation. Further, immunolocalization assays revealed that, similar to PfA-M1, EtAPN1 is present during the intracellular life cycle stages in both the parasite cytoplasm and the parasite nucleus. The present results support the hypothesis of a conserved role between the two aminopeptidases, and we suggest that EtAPN1 might be a valuable target for anticoccidiosis drugs. PMID:24839124

10 CFR 600.20 - Maximum DOE obligation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2011-01-01 2011-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

10 CFR 600.20 - Maximum DOE obligation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2013-01-01 2013-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

10 CFR 600.20 - Maximum DOE obligation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2012-01-01 2012-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

10 CFR 600.20 - Maximum DOE obligation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the amount shown in the award as the amount of DOE funds obligated, and (2) Any designated property. (b) DOE... 10 Energy 4 2014-01-01 2014-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy...

Adult somatic stem cells in the human parasite Schistosoma mansoni.

PubMed

Collins, James J; Wang, Bo; Lambrus, Bramwell G; Tharp, Marla E; Iyer, Harini; Newmark, Phillip A

2013-02-28

Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.

Conventional oil and natural gas infrastructure increases brown-headed cowbird (Molothrus ater) relative abundance and parasitism in mixed-grass prairie

PubMed Central

Nenninger, Heather; Koper, Nicola

2017-01-01

The rapid expansion of oil and natural gas development across the Northern Great Plains has contributed to habitat fragmentation, which may facilitate brood parasitism of ground-nesting grassland songbird nests by brown-headed cowbirds (Molothrus ater), an obligate brood parasite, through the introduction of perches and anthropogenic edges. We tested this hypothesis by measuring brown-headed cowbird relative abundance and brood parasitism rates of Savannah sparrow (Passerculus sandwichensis) nests in relation to the presence of infrastructure features and proximity to potential perches and edge habitat. The presence of oil and natural gas infrastructure increased brown-headed cowbird relative abundance by a magnitude of four times, which resulted in four times greater brood parasitism rates at infrastructure sites. While the presence of infrastructure and the proximity to roads were influential in predicting brood parasitism rates, the proximity of perch sites was not. This suggests that brood parasitism associated with oil and natural gas infrastructure may result in additional pressures that reduce productivity of this declining grassland songbird. PMID:28791134

34 CFR 108.5 - Compliance obligations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Compliance obligations. 108.5 Section 108.5 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION... § 108.5 Compliance obligations. (a) The obligation of covered entities to comply with the Act and this...

The role of egg-nest contrast in the rejection of brood parasitic eggs.

PubMed

Aidala, Zachary; Croston, Rebecca; Schwartz, Jessica; Tong, Lainga; Hauber, Mark E

2015-04-15

Hosts of avian brood parasites can avoid the reproductive costs of raising genetically unrelated offspring by rejecting parasitic eggs. The perceptual cues and controls mediating parasitic egg discrimination and ejection are well studied: hosts are thought to use differences in egg color, brightness, maculation, size and shape to discriminate between their own and foreign eggs. Most theories of brood parasitism implicitly assume that the primary criteria to which hosts attend when discriminating eggs are differences between the eggs themselves. However, this assumption is confounded by the degree to which chromatic and achromatic characteristics of the nest lining co-vary with egg coloration, so that egg-nest contrast per se might be the recognition cue driving parasitic egg detection. Here, we systematically tested whether and how egg-nest contrast itself contributes to foreign egg discrimination. In an artificial parasitism experiment, we independently manipulated egg color and nest lining color of the egg-ejector American robin (Turdus migratorius), a host of the obligate brood parasitic brown-headed cowbird (Molothrus ater). We hypothesized that the degree of contrast between foreign eggs and the nest background would affect host egg rejection behavior. We predicted that experimentally decreasing egg-nest chromatic and achromatic contrast (i.e. rendering parasitic eggs more cryptic against the nest lining) would decrease rejection rates, while increasing egg-nest contrast would increase rejection rates. In contrast to our predictions, egg-nest contrast was not a significant predictor of egg ejection patterns. Instead, egg color significantly predicted responses to parasitism. We conclude that egg-egg differences are the primary drivers of egg rejection in this system. Future studies should test for the effects of egg-nest contrast per se in predicting parasitic egg recognition in other host-parasite systems, including those hosts building enclosed nests and

Fitness Impact of Obligate Intranuclear Bacterial Symbionts Depends on Host Growth Phase

PubMed Central

Bella, Chiara; Koehler, Lars; Grosser, Katrin; Berendonk, Thomas U.; Petroni, Giulio; Schrallhammer, Martina

2016-01-01

According to text book definition, parasites reduce the fitness of their hosts whereas mutualists provide benefits. But biotic and abiotic factors influence symbiotic interactions, thus under certain circumstances parasites can provide benefits and mutualists can harm their host. Here we addressed the question which intrinsic biotic factors shape a symbiosis and are crucial for the outcome of the interaction between the obligate intranuclear bacterium Holospora caryophila (Alphaproteobacteria; Rickettsiales) and its unicellular eukaryotic host Paramecium biaurelia (Alveolata; Ciliophora). The virulence of H. caryophila, i.e., the negative fitness effect on host division and cell number, was determined by growth assays of several P. biaurelia strains. The performances of genetically identical lines either infected with H. caryophila or symbiont-free were compared. Following factors were considered as potentially influencing the outcome of the interaction: (1) host strain, (2) parasite strain, and (3) growth phases of the host. All three factors revealed a strong effect on the symbiosis. In presence of H. caryophila, the Paramecium density in the stationary growth phase decreased. Conversely, a positive effect of the bacteria during the exponential phase was observed for several host × parasite combinations resulting in an increased growth rate of infected P. biaurelia. Furthermore, the fitness impact of the tested endosymbionts on different P. biaurelia lines was not only dependent on one of the two involved strains but distinct for the specific combination. Depending on the current host growth phase, the presence of H. caryophila can be harmful or advantageous for P. biaurelia. Thus, under the tested experimental conditions, the symbionts can switch from the provision of benefits to the exploitation of host resources within the same host population and a time-span of less than 6 days. PMID:28066397

Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection

PubMed Central

Veras, Patrícia Sampaio Tavares; Bezerra de Menezes, Juliana Perrone

2016-01-01

Leishmania is a protozoan parasite that causes a wide range of different clinical manifestations in mammalian hosts. It is a major public health risk on different continents and represents one of the most important neglected diseases. Due to the high toxicity of the drugs currently used, and in the light of increasing drug resistance, there is a critical need to develop new drugs and vaccines to control Leishmania infection. Over the past few years, proteomics has become an important tool to understand the underlying biology of Leishmania parasites and host interaction. The large-scale study of proteins, both in parasites and within the host in response to infection, can accelerate the discovery of new therapeutic targets. By studying the proteomes of host cells and tissues infected with Leishmania, as well as changes in protein profiles among promastigotes and amastigotes, scientists hope to better understand the biology involved in the parasite survival and the host-parasite interaction. This review demonstrates the feasibility of proteomics as an approach to identify new proteins involved in Leishmania differentiation and intracellular survival. PMID:27548150

Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection.

PubMed

Veras, Patrícia Sampaio Tavares; Bezerra de Menezes, Juliana Perrone

2016-08-19

Leishmania is a protozoan parasite that causes a wide range of different clinical manifestations in mammalian hosts. It is a major public health risk on different continents and represents one of the most important neglected diseases. Due to the high toxicity of the drugs currently used, and in the light of increasing drug resistance, there is a critical need to develop new drugs and vaccines to control Leishmania infection. Over the past few years, proteomics has become an important tool to understand the underlying biology of Leishmania parasites and host interaction. The large-scale study of proteins, both in parasites and within the host in response to infection, can accelerate the discovery of new therapeutic targets. By studying the proteomes of host cells and tissues infected with Leishmania, as well as changes in protein profiles among promastigotes and amastigotes, scientists hope to better understand the biology involved in the parasite survival and the host-parasite interaction. This review demonstrates the feasibility of proteomics as an approach to identify new proteins involved in Leishmania differentiation and intracellular survival.

Opposing Biological Functions of Tryptophan Catabolizing Enzymes During Intracellular Infection

PubMed Central

Divanovic, Senad; Sawtell, Nancy M.; Trompette, Aurelien; Warning, Jamie I.; Dias, Alexandra; Cooper, Andrea M.; Yap, George S.; Arditi, Moshe; Shimada, Kenichi; DuHadaway, James B.; Prendergast, George C.; Basaraba, Randall J.; Mellor, Andrew L.; Munn, David H.; Aliberti, Julio

2012-01-01

Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role—antimicrobial or immunoregulatory—is pathogen-specific. PMID:21990421

Global diversity of fish parasitic isopod crustaceans of the family Cymothoidae

PubMed Central

Smit, Nico J.; Bruce, Niel L.; Hadfield, Kerry A.

2014-01-01

Of the 95 known families of Isopoda only a few are parasitic namely, Bopyridae, Cryptoniscidae, Cymothoidae, Dajidae, Entoniscidae, Gnathiidae and Tridentellidae. Representatives from the family Cymothoidae are obligate parasites of both marine and freshwater fishes and there are currently 40 recognised cymothoid genera worldwide. These isopods are large (>6 mm) parasites, thus easy to observe and collect, yet many aspects of their biodiversity and biology are still unknown. They are widely distributed around the world and occur in many different habitats, but mostly in shallow waters in tropical or subtropical areas. A number of adaptations to an obligatory parasitic existence have been observed, such as the body shape, which is influenced by the attachment site on the host. Cymothoids generally have a long, slender body tapering towards the ends and the efficient contour of the body offers minimum resistance to the water flow and can withstand the forces of this particular habitat. Other adaptations to this lifestyle include small sensory antennae and eyes; a very heavily thickened and calcified cuticle for protection; and sharply curved hooks on the ends of the pereopods which allows these parasites to attach to the host. Most cymothoids are highly site and host specific. Some of these parasitic cymothoids have been reported to parasitise the same host fish species for over 100 years, showing this species specificity. The site of attachment on the host (gills, mouth, external surfaces or inside the host flesh) can also be genus or species specific. This paper aims to provide a summary of our current knowledge of cymothoid biodiversity and will highlight their history of discovery, morphology, relationships and classification, taxonomic diversity and ecology. PMID:25180163

Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes.

PubMed

Mauel, J; Buchmüller, Y; Behin, R

1978-08-01

When cultures of normal mouse peritoneal macrophages were infected with the intracellular protozoan parasite Leishmania enrietti, the micro-organism was found to survive intracellularly for several days, apparently without multiplication. However, exposure of infected macrophages to certain stimuli led to rapid parasite killing and digestion, providing a sensitive assay with which the mechanisms of macrophage activation can be studied. Microbicidal activity was induced by incubation of macrophages with syngeneic spleen lymphocytes, which were stimulated either by allogeneic cells in mixed lymphocyte culture (MLC) or by the plant lectin concanavalin A (Con A). Cocultivation with MLCs led to parasite killing within 48-72 h, whereas exposure of infected cells to Con A-stimulated lymphocytes resulted in substantial destruction of the micro-organism within less than 24 h, an effect which was dependent on the presence of thymus-derived lymphocytes and was inhibited by alpha methyl-mannoside. Incubation with Con A-stimulated lymphocytes also led to lysis of part of the macrophage monolayer. However, parasite killing did not result from decreased macrophage survival, as destruction of the micro-organism was highest under culture conditions which were the least detrimental to the phagocytes. Conversely, excess numbers of Con A-stimulated lymphocytes were less efficient at inducing macrophage activation and displayed marked toxicity to the macrophage monolayer. When spleen cells were stimulated by Con A at concentrations above 10 mug/ml, a decrease was noted in the capacity of macrophages to destroy the parasite, probably reflecting a toxicity of the lectin for lymphocytes resulting in impaired activating capacity.

Forward genetic screening identifies a small molecule that blocks Toxoplasma gondii growth by inhibiting both host- and parasite-encoded kinases.

PubMed

Brown, Kevin M; Suvorova, Elena; Farrell, Andrew; McLain, Aaron; Dittmar, Ashley; Wiley, Graham B; Marth, Gabor; Gaffney, Patrick M; Gubbels, Marc Jan; White, Michael; Blader, Ira J

2014-06-01

The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment of intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a host cell transcription factor that is activated by and required for the growth of the intracellular protozoan parasite Toxoplasma gondii at physiological oxygen levels. Parasite activation of HIF-1 is blocked by inhibiting the family of closely related Activin-Like Kinase (ALK) host cell receptors ALK4, ALK5, and ALK7, which was determined in part by use of an ALK4,5,7 inhibitor named SB505124. Besides inhibiting HIF-1 activation, SB505124 also potently blocks parasite replication under normoxic conditions. To determine whether SB505124 inhibition of parasite growth was exclusively due to inhibition of ALK4,5,7 or because the drug inhibited a second kinase, SB505124-resistant parasites were isolated by chemical mutagenesis. Whole-genome sequencing of these mutants revealed mutations in the Toxoplasma MAP kinase, TgMAPK1. Allelic replacement of mutant TgMAPK1 alleles into wild-type parasites was sufficient to confer SB505124 resistance. SB505124 independently impacts TgMAPK1 and ALK4,5,7 signaling since drug resistant parasites could not activate HIF-1 in the presence of SB505124 or grow in HIF-1 deficient cells. In addition, TgMAPK1 kinase activity is inhibited by SB505124. Finally, mice treated with SB505124 had significantly lower tissue burdens following Toxoplasma infection. These data therefore identify SB505124 as a novel small molecule inhibitor that acts by inhibiting two distinct targets, host HIF-1 and TgMAPK1.

Quantitative non-invasive intracellular imaging of Plasmodium falciparum infected human erythrocytes

NASA Astrophysics Data System (ADS)

Edward, Kert; Farahi, Faramarz

2014-05-01

Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition.

Host mitochondrial association evolved in the human parasite Toxoplasma gondii via neofunctionalization of a gene duplicate

USDA-ARS?s Scientific Manuscript database

In Toxoplasma gondii, an intracellular parasite of humans and other warm-blooded animals, the ability to associate with host mitochondria (HMA) is driven by a locally expanded gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. The importance of copy number in the e...

Enrichment of IFN-γ producing cells in different murine adipose tissue depots upon infection with an apicomplexan parasite

PubMed Central

Teixeira, Luzia; Marques, Raquel M.; Ferreirinha, Pedro; Bezerra, Filipa; Melo, Joana; Moreira, João; Pinto, Ana; Correia, Alexandra; Ferreira, Paula G.; Vilanova, Manuel

2016-01-01

Here we report that lean mice infected with the intracellular parasite Neospora caninum show a fast but sustained increase in the frequency of IFN-γ-producing cells noticeable in distinct adipose tissue depots. Moreover, IFN-γ-mediated immune memory could be evoked in vitro in parasite antigen-stimulated adipose tissue stromal vascular fraction cells collected from mice infected one year before. Innate or innate-like cells such as NK, NK T and TCRγδ+ cells, but also CD4+ and CD8+ TCRβ+ lymphocytes contributed to the IFN-γ production observed since day one of infection. This early cytokine production was largely abrogated in IL-12/IL23 p40-deficient mice. Moreover, production of IFN-γ by stromal vascular fraction cells isolated from these mice was markedly lower than that of wild-type counterparts upon stimulation with parasite antigen. In wild-type mice the increased IFN-γ production was concomitant with up-regulated expression of genes encoding interferon-inducible GTPases and nitric oxide synthase, which are important effector molecules in controlling intracellular parasite growth. This increased gene expression was markedly impaired in the p40-deficient mice. Overall, these results show that NK cells but also diverse T cell populations mediate a prompt and widespread production of IFN-γ in the adipose tissue of N. caninum infected mice. PMID:27001522

Memantine, an Antagonist of the NMDA Glutamate Receptor, Affects Cell Proliferation, Differentiation and the Intracellular Cycle and Induces Apoptosis in Trypanosoma cruzi

PubMed Central

Damasceno, Flávia Silva; Barisón, María Julia; Pral, Elisabeth Mieko Furusho; Paes, Lisvane Silva; Silber, Ariel Mariano

2014-01-01

Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and affects approximately 10 million people in endemic areas of Mexico and Central and South America. Currently available chemotherapies are limited to two compounds: Nifurtimox and Benznidazole. Both drugs reduce the symptoms of the disease and mortality among infected individuals when used during the acute phase, but their efficacy during the chronic phase (during which the majority of cases are diagnosed) remains controversial. Moreover, these drugs have several side effects. The aim of this study was to evaluate the effect of Memantine, an antagonist of the glutamate receptor in the CNS of mammals, on the life cycle of T. cruzi. Memantine exhibited a trypanocidal effect, inhibiting the proliferation of epimastigotes (IC50 172.6 µM). Furthermore, this compound interfered with metacyclogenesis (approximately 30% reduction) and affected the energy metabolism of the parasite. In addition, Memantine triggered mechanisms that led to the apoptosis-like cell death of epimastigotes, with extracellular exposure of phosphatidylserine, increased production of reactive oxygen species, decreased ATP levels, increased intracellular Ca2+ and morphological changes. Moreover, Memantine interfered with the intracellular cycle of the parasite, specifically the amastigote stage (IC50 31 µM). Interestingly, the stages of the parasite life cycle that require more energy (epimastigote and amastigote) were more affected as were the processes of differentiation and cell invasion. PMID:24587468

Antibiotic susceptibility and intracellular localization of Diplorickettsia massiliensis.

PubMed

Subramanian, Geetha; Barry, Abdoulaye O; Ghigo, Eric; Raoult, Didier; Mediannikov, Oleg

2012-02-01

Diplorickettsia massiliensis is an obligate intracellular bacterium from the Coxiellaceae family recently isolated from Ixodes ricinus ticks. The inhibitory effects of antimicrobial agents were assessed by two different methods, immunofluorescence and Gimenez staining assay. Different markers (EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99) were used to reveal the nature of the vacuole containing the bacterium. Ciprofloxacin, levofloxacin, and rifampin had MIC values of 2 lg mL(-1). We found that 4 lg mL(-1) of Doxycycline inhibited the growth of D. massiliensis strain. Surprisingly, D. massiliensis was resistant to chloramphenicol up to the concentration of 64 lg mL(-1). We found that penicillin G, ammonium chloride, gentamycin, omeprazole, bafilomycin A1, and chloroquine were not active against D. massiliensis. Studies performed with markers EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99 showed that D. massiliensis is localized within an acidic compartment that is not an early phagosome, but a late phagosome or a phagolysosome. Gimenez staining stays a good method that will work with a very low number of bacteria and can be used to determine the MICs of new therapeutic antibiotics precisely. The resistance profile of D. massiliensis was found to be quite unusual for intracellular Gram-negative bacterium with marked resistance to chloramphenicol. Despite of localization in acidic compartment, pH-neutralizing agents do not significantly inhibit intracellular growth of bacterium. The results of these studies prove that antibiotic resistance does not depend on pH of vacuole. This pH-related mechanism seems not to play a contributing role in the overall resistance of D. massiliensis.

Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa.

PubMed

Mendes, Antonio M; Schlegelmilch, Timm; Cohuet, Anna; Awono-Ambene, Parfait; De Iorio, Maria; Fontenille, Didier; Morlais, Isabelle; Christophides, George K; Kafatos, Fotis C; Vlachou, Dina

2008-05-16

In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists.

29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 1 2012-07-01 2012-07-01 false How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 1 2014-07-01 2013-07-01 true How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 1 2011-07-01 2011-07-01 false How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

29 CFR 37.21 - How long will the recipient's obligation under the assurance last, and how broad is the obligation?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 1 2013-07-01 2013-07-01 false How long will the recipient's obligation under the assurance last, and how broad is the obligation? 37.21 Section 37.21 Labor Office of the Secretary of Labor...'s obligation under the assurance last, and how broad is the obligation? (a) Where the WIA Title I...

Seed germination in parasitic plants: what insights can we expect from strigolactone research?

PubMed

Brun, Guillaume; Braem, Lukas; Thoiron, Séverine; Gevaert, Kris; Goormachtig, Sofie; Delavault, Philippe

2018-04-23

Obligate root-parasitic plants belonging to the Orobanchaceae family are deadly pests for major crops all over the world. Because these heterotrophic plants severely damage their hosts even before emerging from the soil, there is an unequivocal need to design early and efficient methods for their control. The germination process of these species has probably undergone numerous selective pressure events in the course of evolution, in that the perception of host-derived molecules is a necessary condition for seeds to germinate. Although most of these molecules belong to the strigolactones, structurally different molecules have been identified. Since strigolactones are also classified as novel plant hormones that regulate several physiological processes other than germination, the use of autotrophic model plant species has allowed the identification of many actors involved in the strigolactone biosynthesis, perception, and signal transduction pathways. Nevertheless, many questions remain to be answered regarding the germination process of parasitic plants. For instance, how did parasitic plants evolve to germinate in response to a wide variety of molecules, while autotrophic plants do not? What particular features are associated with their lack of spontaneous germination? In this review, we attempt to illustrate to what extent conclusions from research into strigolactones could be applied to better understand the biology of parasitic plants.

Possible Synergistic Effects of Thymol and Nicotine Against Crithidia bombi Parasitism in Bumble Bees.

PubMed

Biller, Olivia Masi; Adler, Lynn S; Irwin, Rebecca E; McAllister, Caitlin; Palmer-Young, Evan C

2015-01-01

Floral nectar contains secondary compounds with antimicrobial properties that can affect not only plant-pollinator interactions, but also interactions between pollinators and their parasites. Although recent work has shown that consumption of plant secondary compounds can reduce pollinator parasite loads, little is known about the effects of dosage or compound combinations. We used the generalist pollinator Bombus impatiens and its obligate gut parasite Crithidia bombi to study the effects of nectar chemistry on host-parasite interactions. In two experiments we tested (1) whether the secondary compounds thymol and nicotine act synergistically to reduce parasitism, and (2) whether dietary thymol concentration affects parasite resistance. In both experiments, uninfected Bombus impatiens were inoculated with Crithidia and then fed particular diet treatments for 7 days, after which infection levels were assessed. In the synergism experiment, thymol and nicotine alone and in combination did not significantly affect parasite load or host mortality. However, the thymol-nicotine combination treatment reduced log-transformed parasite counts by 30% relative to the control group (P = 0.08). For the experiment in which we manipulated thymol concentration, we found no significant effect of any thymol concentration on Crithidia load, but moderate (2 ppm) thymol concentrations incurred a near-significant increase in mortality (P = 0.054). Our results tentatively suggest the value of a mixed diet for host immunity, yet contrast with research on the antimicrobial activity of dietary thymol and nicotine in vertebrate and other invertebrate systems. We suggest that future research evaluate genetic variation in Crithidia virulence, multi-strain competition, and Crithidia interactions with the gut microbe community that may mediate antimicrobial activities of secondary compounds.

Possible Synergistic Effects of Thymol and Nicotine against Crithidia bombi Parasitism in Bumble Bees

PubMed Central

Adler, Lynn S.; Irwin, Rebecca E.; McAllister, Caitlin

2015-01-01

Floral nectar contains secondary compounds with antimicrobial properties that can affect not only plant-pollinator interactions, but also interactions between pollinators and their parasites. Although recent work has shown that consumption of plant secondary compounds can reduce pollinator parasite loads, little is known about the effects of dosage or compound combinations. We used the generalist pollinator Bombus impatiens and its obligate gut parasite Crithidia bombi to study the effects of nectar chemistry on host-parasite interactions. In two experiments we tested (1) whether the secondary compounds thymol and nicotine act synergistically to reduce parasitism, and (2) whether dietary thymol concentration affects parasite resistance. In both experiments, uninfected Bombus impatiens were inoculated with Crithidia and then fed particular diet treatments for 7 days, after which infection levels were assessed. In the synergism experiment, thymol and nicotine alone and in combination did not significantly affect parasite load or host mortality. However, the thymol-nicotine combination treatment reduced log-transformed parasite counts by 30% relative to the control group (P = 0.08). For the experiment in which we manipulated thymol concentration, we found no significant effect of any thymol concentration on Crithidia load, but moderate (2 ppm) thymol concentrations incurred a near-significant increase in mortality (P = 0.054). Our results tentatively suggest the value of a mixed diet for host immunity, yet contrast with research on the antimicrobial activity of dietary thymol and nicotine in vertebrate and other invertebrate systems. We suggest that future research evaluate genetic variation in Crithidia virulence, multi-strain competition, and Crithidia interactions with the gut microbe community that may mediate antimicrobial activities of secondary compounds. PMID:26657643

Massive mitochondrial gene transfer in a parasitic flowering plant clade.

PubMed

Xi, Zhenxiang; Wang, Yuguo; Bradley, Robert K; Sugumaran, M; Marx, Christopher J; Rest, Joshua S; Davis, Charles C

2013-01-01

Recent studies have suggested that plant genomes have undergone potentially rampant horizontal gene transfer (HGT), especially in the mitochondrial genome. Parasitic plants have provided the strongest evidence of HGT, which appears to be facilitated by the intimate physical association between the parasites and their hosts. A recent phylogenomic study demonstrated that in the holoparasite Rafflesia cantleyi (Rafflesiaceae), whose close relatives possess the world's largest flowers, about 2.1% of nuclear gene transcripts were likely acquired from its obligate host. Here, we used next-generation sequencing to obtain the 38 protein-coding and ribosomal RNA genes common to the mitochondrial genomes of angiosperms from R. cantleyi and five additional species, including two of its closest relatives and two host species. Strikingly, our phylogenetic analyses conservatively indicate that 24%-41% of these gene sequences show evidence of HGT in Rafflesiaceae, depending on the species. Most of these transgenic sequences possess intact reading frames and are actively transcribed, indicating that they are potentially functional. Additionally, some of these transgenes maintain synteny with their donor and recipient lineages, suggesting that native genes have likely been displaced via homologous recombination. Our study is the first to comprehensively assess the magnitude of HGT in plants involving a genome (i.e., mitochondria) and a species interaction (i.e., parasitism) where it has been hypothesized to be potentially rampant. Our results establish for the first time that, although the magnitude of HGT involving nuclear genes is appreciable in these parasitic plants, HGT involving mitochondrial genes is substantially higher. This may represent a more general pattern for other parasitic plant clades and perhaps more broadly for angiosperms.

Interactions between environmental stressors: the influence of salinity on host-parasite interactions between Daphnia magna and Pasteuria ramosa.

PubMed

Hall, Matthew D; Vettiger, Andrea; Ebert, Dieter

2013-04-01

Interactions between environmental stressors play an important role in shaping the health of an organism. This is particularly true in terms of the prevalence and severity of infectious disease, as stressors in combination will not always act to simply decrease the immune function of a host, but may instead interact to compound or even oppose the influence of parasitism on the health of an organism. Here, we explore the impact of environmental stress on host-parasite interactions using the water flea Daphnia magna and it is obligate parasite Pasteuria ramosa. Utilising an ecologically relevant stressor, we focus on the combined effect of salinity and P. ramosa on the fecundity and survival of the host, as well as on patterns of infectivity and the proliferation of the parasite. We show that in the absence of the parasite, host fecundity and survival was highest in the low salinity treatments. Once a parasite was introduced into the environment, however, salinity and parasitism acted antagonistically to influence both host survival and fecundity, and these patterns of disease were unrelated to infection rates or parasite spore loads. By summarising the form of interactions found in the broader Daphnia literature, we highlight how the combined effect of stress and parasitism will vary with the type of stressor, the trait used to describe the health of Daphnia and the host-parasite combination under observation. Our results highlight how the context-dependent nature of interactions between stress and parasitism inevitably complicates the link between environmental factors and the prevalence and severity of disease.

H2O2 dynamics in the malaria parasite Plasmodium falciparum

PubMed Central

Rahbari, Mahsa; Bogeski, Ivan

2017-01-01

Hydrogen peroxide is an important antimicrobial agent but is also crucially involved in redox signaling and pathogen-host cell interactions. As a basis for systematically investigating intracellular H2O2 dynamics and regulation in living malaria parasites, we established the genetically encoded fluorescent H2O2 sensors roGFP2-Orp1 and HyPer-3 in Plasmodium falciparum. Both ratiometric redox probes as well as the pH control SypHer were expressed in the cytosol of blood-stage parasites. Both redox sensors showed reproducible sensitivity towards H2O2 in the lower micromolar range in vitro and in the parasites. Due to the pH sensitivity of HyPer-3, we used parasites expressing roGFP2-Orp1 for evaluation of short-, medium-, and long-term effects of antimalarial drugs on H2O2 levels and detoxification in Plasmodium. None of the quinolines or artemisinins tested had detectable direct effects on the H2O2 homeostasis at pharmacologically relevant concentrations. However, pre-treatment of the cells with antimalarial drugs or heat shock led to a higher tolerance towards exogenous H2O2. The systematic evaluation and comparison of the two genetically encoded cytosolic H2O2 probes in malaria parasites provides a basis for studying parasite-host cell interactions or drug effects with spatio-temporal resolution while preserving cell integrity. PMID:28369083

Evaluation of a Novel Magneto-Optical Method for the Detection of Malaria Parasites

PubMed Central

Orbán, Ágnes; Butykai, Ádám; Molnár, András; Pröhle, Zsófia; Fülöp, Gergö; Zelles, Tivadar; Forsyth, Wasan; Hill, Danika; Müller, Ivo; Schofield, Louis; Rebelo, Maria; Hänscheid, Thomas; Karl, Stephan; Kézsmárki, István

2014-01-01

Improving the efficiency of malaria diagnosis is one of the main goals of current malaria research. We have recently developed a magneto-optical (MO) method which allows high-sensitivity detection of malaria pigment (hemozoin crystals) in blood via the magnetically induced rotational motion of the hemozoin crystals. Here, we evaluate this MO technique for the detection of Plasmodium falciparum in infected erythrocytes using in-vitro parasite cultures covering the entire intraerythrocytic life cycle. Our novel method detected parasite densities as low as ∼40 parasites per microliter of blood (0.0008% parasitemia) at the ring stage and less than 10 parasites/µL (0.0002% parasitemia) in the case of the later stages. These limits of detection, corresponding to approximately 20 pg/µL of hemozoin produced by the parasites, exceed that of rapid diagnostic tests and compete with the threshold achievable by light microscopic observation of blood smears. The MO diagnosis requires no special training of the operator or specific reagents for parasite detection, except for an inexpensive lysis solution to release intracellular hemozoin. The devices can be designed to a portable format for clinical and in-field tests. Besides testing its diagnostic performance, we also applied the MO technique to investigate the change in hemozoin concentration during parasite maturation. Our preliminary data indicate that this method may offer an efficient tool to determine the amount of hemozoin produced by the different parasite stages in synchronized cultures. Hence, it could eventually be used for testing the susceptibility of parasites to antimalarial drugs. PMID:24824542

Grandparents' entitlements and obligations.

PubMed

Draper, Heather

2013-07-01

In this article, it is argued that grandparents' obligations originate from parental obligations (i.e from the relationship they have with their children, the parents of their grandchildren) and not from the role of grandparent per se, and any entitlements flow from the extent to which these obligations are met. The position defended is, therefore, that grandparents qua grandparents are not entitled to form or continue relationships with their grandchildren. A continuation of grandparent-grandchildren relationships may be in the interests of children, but the grandparental nature of the relationship is not decisive. What counts is the extent to which relationships children have with any adults who are not their parents are is significant to them. Sometimes, however, grandparents become parents or co-parents of their grandchildren. They then gain parental rights, and as such are as entitled, ceteris parius, as any parent to expect their relationship with the child to continue. The issue of grandparents' entitlements can come to the fore when parents separate, and grandparents are unhappy with the access they have to their grandchildren. Grandparents' obligations may become a particular issue when parents die, struggle, or fail to care for their children. This article focuses particularly on these kinds of circumstances. © 2013 John Wiley & Sons Ltd.

GRANDPARENTS' ENTITLEMENTS AND OBLIGATIONS

PubMed Central

Draper, Heather

2013-01-01

In this article, it is argued that grandparents' obligations originate from parental obligations (i.e from the relationship they have with their children, the parents of their grandchildren) and not from the role of grandparent per se, and any entitlements flow from the extent to which these obligations are met. The position defended is, therefore, that grandparents qua grandparents are not entitled to form or continue relationships with their grandchildren. A continuation of grandparent-grandchildren relationships may be in the interests of children, but the grandparental nature of the relationship is not decisive. What counts is the extent to which relationships children have with any adults who are not their parents are is significant to them. Sometimes, however, grandparents become parents or co-parents of their grandchildren. They then gain parental rights, and as such are as entitled, ceteris parius, as any parent to expect their relationship with the child to continue. The issue of grandparents' entitlements can come to the fore when parents separate, and grandparents are unhappy with the access they have to their grandchildren. Grandparents' obligations may become a particular issue when parents die, struggle, or fail to care for their children. This article focuses particularly on these kinds of circumstances. PMID:23718643

Molecular genetic transfection of the coccidian parasite Sarcocystis neurona.

PubMed

Gaji, Rajshekhar Y; Zhang, Deqing; Breathnach, Cormac C; Vaishnava, Shipra; Striepen, Boris; Howe, Daniel K

2006-11-01

Sarcocystis neurona is an apicomplexan parasite that is the major cause of equine protozoal myeloencephalitis (EPM). The biology of this pathogen remains poorly understood in part due to unavailability of molecular genetic tools. Hence, with an objective to develop DNA transfection capabilities for S. neurona, the 5' flanking region of the SnSAG1 gene was isolated from a genomic library and used to construct expression plasmids. In transient assays, the reporter molecules beta-galactosidase (beta-gal) and yellow fluorescent protein (YFP) could be detected in electroporated S. neurona, thereby confirming the feasibility of transgene expression in this organism. Stable transformation of S. neurona was achieved using a mutant dihydrofolate reductase thymidylate synthase (DHFR-TS) gene of Toxoplasma gondii that confers resistance to pyrimethamine. This selection system was used to create transgenic S. neurona that stably express beta-gal and YFP. As shown in this study, these transgenic clones can be useful for analyzing growth rate of parasites in vitro and for assessing drug sensitivities. More importantly, the DNA transfection methods described herein should greatly facilitate studies examining intracellular parasitism by this important coccidian pathogen.

31 CFR 149.3 - Maximum obligation limitation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Maximum obligation limitation. 149.3 Section 149.3 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES, DEPARTMENT OF THE TREASURY CALCULATION OF MAXIMUM OBLIGATION LIMITATION § 149.3 Maximum obligation limitation...

10 CFR 600.20 - Maximum DOE obligation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Maximum DOE obligation. 600.20 Section 600.20 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS FINANCIAL ASSISTANCE RULES General § 600.20 Maximum DOE obligation. (a) The maximum DOE obligation to the recipient is— (1) For monetary awards, the...

Modeling effective transmission pathways and control of the world's most successful parasite.

PubMed

Turner, Matthew; Lenhart, Suzanne; Rosenthal, Benjamin; Zhao, Xiaopeng

2013-06-01

Toxoplasma gondii(T. gondii) is a single-celled, intracellular protozoan responsible for the disease toxoplasmosis. The parasite is prevalent worldwide, and it infects all warm-blooded vertebrates. Consumption of meats in which this parasite has encysted confers risk of infection to people and other animals, as does ingestion of water or foods contaminated with environmentally resistant oocysts excreted by cats. Vertical transmission (from mother to offspring) is also possible, leading to disease risk and contributing additional means of ensuring perpetuation of transmission. In this work, we adopt a differential equation model to investigate the effective transmission pathways of T. gondii, as well as potential control mechanisms. Detailed analyses are carried out to examine the significance of transmission routes, virulence, vertical transmission, parasite-induced changes in host behavior, and controls based on vaccination and harvesting. Modeling and analysis efforts may shed insights into understanding the complex life cycle of T. gondii. Copyright © 2013 Elsevier Inc. All rights reserved.

46 CFR 287.20 - Obligation of deposits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Obligation of deposits. 287.20 Section 287.20 Shipping... OPERATORS ESTABLISHMENT OF CONSTRUCTION RESERVE FUNDS § 287.20 Obligation of deposits. (a) Time for obligation. Within three years from the date of any deposit in a construction reserve fund, unless extension...

Phylogenetic relationship of Hepatozoon blood parasites found in snakes from Africa, America and Asia.

PubMed

Haklová, B; Majláthová, V; Majláth, I; Harris, D J; Petrilla, V; Litschka-Koen, T; Oros, M; Peťko, B

2014-03-01

The blood parasites from the genus Hepatozoon Miller, 1908 (Apicomplexa: Adeleida: Hepatozoidae) represent the most common intracellular protozoan parasites found in snakes. In the present study, we examined 209 individuals of snakes, from different zoogeographical regions (Africa, America, Asia and Europe), for the occurrence of blood parasites using both molecular and microscopic examination methods, and assess phylogenetic relationships of all Hepatozoon parasites from snakes for the first time. In total, 178 blood smears obtained from 209 individuals, representing 40 species, were examined, from which Hepatozoon unicellular parasites were found in 26 samples (14·6% prevalence). Out of 180 samples tested by molecular method polymerase chain reaction (PCR), the presence of parasites was observed in 21 individuals (prevalence 11·6%): 14 snakes from Africa belonging to six genera (Dendroaspis, Dispholidus, Mehelya, Naja, Philothamnus and Python), five snakes from Asia from the genus Morelia and two snakes from America, from two genera (Coluber and Corallus). The intensity of infection varied from one to 1433 infected cells per 10 000 erythrocytes. Results of phylogenetic analyses (Bayesian and Maximum Likelihood) revealed the existence of five haplotypes divided into four main lineages. The present data also indicate neither geographical pattern of studied Hepatozoon sp., nor congruency in the host association.

Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells

PubMed Central

Romero-Brey, Inés; Bartenschlager, Ralf

2015-01-01

As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications. PMID:26633469

Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells.

PubMed

Romero-Brey, Inés; Bartenschlager, Ralf

2015-12-03

As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications.

Microsporidia infection impacts the host cell's cycle and reduces host cell apoptosis.

PubMed

Martín-Hernández, Raquel; Higes, Mariano; Sagastume, Soledad; Juarranz, Ángeles; Dias-Almeida, Joyce; Budge, Giles E; Meana, Aránzazu; Boonham, Neil

2017-01-01

Intracellular parasites can alter the cellular machinery of host cells to create a safe haven for their survival. In this regard, microsporidia are obligate intracellular fungal parasites with extremely reduced genomes and hence, they are strongly dependent on their host for energy and resources. To date, there are few studies into host cell manipulation by microsporidia, most of which have focused on morphological aspects. The microsporidia Nosema apis and Nosema ceranae are worldwide parasites of honey bees, infecting their ventricular epithelial cells. In this work, quantitative gene expression and histology were studied to investigate how these two parasites manipulate their host's cells at the molecular level. Both these microsporidia provoke infection-induced regulation of genes involved in apoptosis and the cell cycle. The up-regulation of buffy (which encodes a pro-survival protein) and BIRC5 (belonging to the Inhibitor Apoptosis protein family) was observed after infection, shedding light on the pathways that these pathogens use to inhibit host cell apoptosis. Curiously, different routes related to cell cycle were modified after infection by each microsporidia. In the case of N. apis, cyclin B1, dacapo and E2F2 were up-regulated, whereas only cyclin E was up-regulated by N. ceranae, in both cases promoting the G1/S phase transition. This is the first report describing molecular pathways related to parasite-host interactions that are probably intended to ensure the parasite's survival within the cell.

Phylogeography of the ant Myrmica rubra and its inquiline social parasite

PubMed Central

Leppänen, Jenni; Vepsäläinen, Kari; Savolainen, Riitta

2011-01-01

Widely distributed Palearctic insects are ideal to study phylogeographic patterns owing to their high potential to survive in many Pleistocene refugia and—after the glaciation—to recolonize vast, continuous areas. Nevertheless, such species have received little phylogeographic attention. Here, we investigated the Pleistocene refugia and subsequent postglacial colonization of the common, abundant, and widely distributed ant Myrmica rubra over most of its Palearctic area, using mitochondrial DNA (mtDNA). The western and eastern populations of M. rubra belonged predominantly to separate haplogroups, which formed a broad secondary contact zone in Central Europe. The distribution of genetic diversity and haplogroups implied that M. rubra survived the last glaciation in multiple refugia located over an extensive area from Iberia in the west to Siberia in the east, and colonized its present areas of distribution along several routes. The matrilineal genetic structure of M. rubra was probably formed during the last glaciation and subsequent postglacial expansion. Additionally, because M. rubra has two queen morphs, the obligately socially parasitic microgyne and its macrogyne host, we tested the suggested speciation of the parasite. Locally, the parasite and host usually belonged to the same haplogroup but differed in haplotype frequencies. This indicates that genetic differentiation between the morphs is a universal pattern and thus incipient, sympatric speciation of the parasite from its host is possible. If speciation is taking place, however, it is not yet visible as lineage sorting of the mtDNA between the morphs. PMID:22393482

The Ditylenchus destructor genome provides new insights into the evolution of plant parasitic nematodes

PubMed Central

Zheng, Jinshui; Peng, Donghai; Chen, Ling; Liu, Hualin; Chen, Feng; Xu, Mengci; Ju, Shouyong; Ruan, Lifang

2016-01-01

Plant-parasitic nematodes were found in 4 of the 12 clades of phylum Nematoda. These nematodes in different clades may have originated independently from their free-living fungivorous ancestors. However, the exact evolutionary process of these parasites is unclear. Here, we sequenced the genome sequence of a migratory plant nematode, Ditylenchus destructor. We performed comparative genomics among the free-living nematode, Caenorhabditis elegans and all the plant nematodes with genome sequences available. We found that, compared with C. elegans, the core developmental control processes underwent heavy reduction, though most signal transduction pathways were conserved. We also found D. destructor contained more homologies of the key genes in the above processes than the other plant nematodes. We suggest that Ditylenchus spp. may be an intermediate evolutionary history stage from free-living nematodes that feed on fungi to obligate plant-parasitic nematodes. Based on the facts that D. destructor can feed on fungi and has a relatively short life cycle, and that it has similar features to both C. elegans and sedentary plant-parasitic nematodes from clade 12, we propose it as a new model to study the biology, biocontrol of plant nematodes and the interaction between nematodes and plants. PMID:27466450

The Ditylenchus destructor genome provides new insights into the evolution of plant parasitic nematodes.

PubMed

Zheng, Jinshui; Peng, Donghai; Chen, Ling; Liu, Hualin; Chen, Feng; Xu, Mengci; Ju, Shouyong; Ruan, Lifang; Sun, Ming

2016-07-27

Plant-parasitic nematodes were found in 4 of the 12 clades of phylum Nematoda. These nematodes in different clades may have originated independently from their free-living fungivorous ancestors. However, the exact evolutionary process of these parasites is unclear. Here, we sequenced the genome sequence of a migratory plant nematode, Ditylenchus destructor We performed comparative genomics among the free-living nematode, Caenorhabditis elegans and all the plant nematodes with genome sequences available. We found that, compared with C. elegans, the core developmental control processes underwent heavy reduction, though most signal transduction pathways were conserved. We also found D. destructor contained more homologies of the key genes in the above processes than the other plant nematodes. We suggest that Ditylenchus spp. may be an intermediate evolutionary history stage from free-living nematodes that feed on fungi to obligate plant-parasitic nematodes. Based on the facts that D. destructor can feed on fungi and has a relatively short life cycle, and that it has similar features to both C. elegans and sedentary plant-parasitic nematodes from clade 12, we propose it as a new model to study the biology, biocontrol of plant nematodes and the interaction between nematodes and plants. © 2016 The Author(s).

microRNAs in parasites and parasite infection

PubMed Central

Zheng, Yadong; Cai, Xuepeng; Bradley, Janette E.

2013-01-01

miRNAs, a subclass of small regulatory RNAs, are present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. The miRNA-silencing mechanism appears, however, to be absent in a number of protozoan parasites. Protozoan miRNAs and components of their silencing machinery possess features different from other eukaryotes, providing some clues on the evolution of the RNA-induced silencing machinery. miRNA functions possibly associate with neoblast biology, development, physiology, infection and immunity of parasites. Parasite infection can alter host miRNA expression that can favor both parasite clearance and infection. miRNA pathways are, thus, a potential target for the therapeutic control of parasitic diseases. PMID:23392243

United States Department of Agriculture-Agricultural Research Service research programs on microbes for management of plant-parasitic nematodes.

PubMed

Meyer, Susan L F

2003-01-01

Restrictions on the use of conventional nematicides have increased the need for new methods of managing plant-parasitic nematodes. Consequently, nematode-antagonistic microbes, and active compounds produced by such organisms, are being explored as potential additions to management practices. Programs in this area at the USDA Agricultural Research Service investigate applied biocontrol agents, naturally occurring beneficial soil microbes and natural compounds. Specific research topics include use of plant growth-promoting rhizobacteria and cultural practices for management of root-knot and ring nematodes, determination of management strategies that enhance activity of naturally occurring Pasteuria species (bacterial obligate parasites of nematodes), studies on interactions between biocontrol bacteria and bacterial-feeding nematodes, and screening of microbes for compounds active against plant-parasitic nematodes. Some studies involve biocontrol agents that are active against nematodes and soil-borne plant-pathogenic fungi, or combinations of beneficial bacteria and fungi, to manage a spectrum of plant diseases or to increase efficacy over a broader range of environmental conditions. Effective methods or agents identified in the research programs are investigated as additions to existing management systems for plant-parasitic nematodes.

Sexual imprinting misguides species recognition in a facultative interspecific brood parasite

PubMed Central

Sorenson, Michael D.; Hauber, Mark E.; Derrickson, Scott R.

2010-01-01

Sexual reproduction relies on the recognition of conspecifics for breeding. Most experiments in birds have implicated a critical role for early social learning in directing subsequent courtship behaviours and mating decisions. This classical view of avian sexual imprinting is challenged, however, by studies of megapodes and obligate brood parasites, species in which reliable recognition is achieved despite the lack of early experience with conspecifics. By rearing males with either conspecific or heterospecific brood mates, we experimentally tested the effect of early social experience on the association preferences and courtship behaviours of two sympatrically breeding ducks. We predicted that redheads (Aythya americana), which are facultative interspecific brood parasites, would show a diminished effect of early social environment on subsequent courtship preferences when compared with their host and congener, the canvasback (Aythya valisineria). Contrary to expectations, cross-fostered males of both species courted heterospecific females and preferred them in spatial association tests, whereas control males courted and associated with conspecific females. These results imply that ontogenetic constraints on species recognition may be a general impediment to the initial evolution of interspecific brood parasitism in birds. Under more natural conditions, a variety of mechanisms may mitigate or counteract the effects of early imprinting for redheads reared in canvasback broods. PMID:20484239

Sexual imprinting misguides species recognition in a facultative interspecific brood parasite.

PubMed

Sorenson, Michael D; Hauber, Mark E; Derrickson, Scott R

2010-10-22

Sexual reproduction relies on the recognition of conspecifics for breeding. Most experiments in birds have implicated a critical role for early social learning in directing subsequent courtship behaviours and mating decisions. This classical view of avian sexual imprinting is challenged, however, by studies of megapodes and obligate brood parasites, species in which reliable recognition is achieved despite the lack of early experience with conspecifics. By rearing males with either conspecific or heterospecific brood mates, we experimentally tested the effect of early social experience on the association preferences and courtship behaviours of two sympatrically breeding ducks. We predicted that redheads (Aythya americana), which are facultative interspecific brood parasites, would show a diminished effect of early social environment on subsequent courtship preferences when compared with their host and congener, the canvasback (Aythya valisineria). Contrary to expectations, cross-fostered males of both species courted heterospecific females and preferred them in spatial association tests, whereas control males courted and associated with conspecific females. These results imply that ontogenetic constraints on species recognition may be a general impediment to the initial evolution of interspecific brood parasitism in birds. Under more natural conditions, a variety of mechanisms may mitigate or counteract the effects of early imprinting for redheads reared in canvasback broods.

Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of Plasmodium falciparum.

PubMed

Suárez-Cortés, Pablo; Gambara, Guido; Favia, Annarita; Palombi, Fioretta; Alano, Pietro; Filippini, Antonio

2017-09-12

Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca 2+ signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs. This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca 2+ release (Ned-19) on P. falciparum, revealing the inhibitory effect of this compound on the blood stage development of this parasite. Ned-19 inhibits both the transition of the parasite from the early to the late trophozoite stage and the ability of the late trophozoite to develop to the multinucleated schizont stage. In addition, Ned-19 affects spontaneous intracellular Ca 2+ oscillations in ring and trophozoite stage parasites, suggesting that the observed inhibitory effects may be associated to regulation of intracellular Ca 2+ levels. This study highlights the inhibitory effect of Ned-19 on progression of the asexual life cycle of P. falciparum. The observation that Ned-19 inhibits spontaneous Ca 2+ oscillations suggests a potential role of NAADP in regulating Ca 2+ signalling of P. falciparum.

Cancer Moonshot Funding Obligations FY 2017

Cancer.gov

NCI reports Cancer Moonshot obligations by funding mechanism. See obligations for Moonshot grants, intramural research, and contracts, including the number of grant awards, funding amounts, and percentages by mechanism of the total Cancer Moonshot budget.

Host lignin composition affects haustorium induction in the parasitic plants Phtheirospermum japonicum and Striga hermonthica.

PubMed

Cui, Songkui; Wada, Syogo; Tobimatsu, Yuki; Takeda, Yuri; Saucet, Simon B; Takano, Toshiyuki; Umezawa, Toshiaki; Shirasu, Ken; Yoshida, Satoko

2018-04-01

Parasitic plants in the family Orobanchaceae are destructive weeds of agriculture worldwide. The haustorium, an essential parasitic organ used by these plants to penetrate host tissues, is induced by host-derived phenolic compounds called haustorium-inducing factors (HIFs). The origin of HIFs remains unknown, although the structures of lignin monomers resemble that of HIFs. Lignin is a natural phenylpropanoid polymer, commonly found in secondary cell walls of vascular plants. We therefore investigated the possibility that HIFs are derived from host lignin. Various lignin-related phenolics, quinones and lignin polymers, together with nonhost and host plants that have different lignin compositions, were tested for their haustorium-inducing activity in two Orobanchaceae species, a facultative parasite, Phtheirospermum japonicum, and an obligate parasite, Striga hermonthica. Lignin-related compounds induced haustoria in P. japonicum and S. hermonthica with different specificities. High concentrations of lignin polymers induced haustorium formation. Treatment with laccase, a lignin degradation enzyme, promoted haustorium formation at low concentrations. The distinct lignin compositions of the host and nonhost plants affected haustorium induction, correlating with the response of the different parasitic plants to specific types of lignin-related compounds. Our study provides valuable insights into the important roles of lignin biosynthesis and degradation in the production of HIFs. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Wholly Rickettsia! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells

PubMed Central

Driscoll, Timothy P.; Verhoeve, Victoria I.; Guillotte, Mark L.; Lehman, Stephanie S.; Rennoll, Sherri A.; Beier-Sexton, Magda; Rahman, M. Sayeedur; Azad, Abdu F.

2017-01-01

ABSTRACT Reductive genome evolution has purged many metabolic pathways from obligate intracellular Rickettsia (Alphaproteobacteria; Rickettsiaceae). While some aspects of host-dependent rickettsial metabolism have been characterized, the array of host-acquired metabolites and their cognate transporters remains unknown. This dearth of information has thwarted efforts to obtain an axenic Rickettsia culture, a major impediment to conventional genetic approaches. Using phylogenomics and computational pathway analysis, we reconstructed the Rickettsia metabolic and transport network, identifying 51 host-acquired metabolites (only 21 previously characterized) needed to compensate for degraded biosynthesis pathways. In the absence of glycolysis and the pentose phosphate pathway, cell envelope glycoconjugates are synthesized from three imported host sugars, with a range of additional host-acquired metabolites fueling the tricarboxylic acid cycle. Fatty acid and glycerophospholipid pathways also initiate from host precursors, and import of both isoprenes and terpenoids is required for the synthesis of ubiquinone and the lipid carrier of lipid I and O-antigen. Unlike metabolite-provisioning bacterial symbionts of arthropods, rickettsiae cannot synthesize B vitamins or most other cofactors, accentuating their parasitic nature. Six biosynthesis pathways contain holes (missing enzymes); similar patterns in taxonomically diverse bacteria suggest alternative enzymes that await discovery. A paucity of characterized and predicted transporters emphasizes the knowledge gap concerning how rickettsiae import host metabolites, some of which are large and not known to be transported by bacteria. Collectively, our reconstructed metabolic network offers clues to how rickettsiae hijack host metabolic pathways. This blueprint for growth determinants is an important step toward the design of axenic media to rescue rickettsiae from the eukaryotic cell. PMID:28951473

Increased Ca++ uptake by erythrocytes infected with malaria parasites: Evidence for exported proteins and novel inhibitors.

PubMed

Kushwaha, Ambuj K; Apolis, Liana; Ito, Daisuke; Desai, Sanjay A

2018-05-03

Malaria parasites export many proteins into their host erythrocytes and increase membrane permeability to diverse solutes. Although most solutes use a broad-selectivity channel known as the plasmodial surface anion channel, increased Ca ++ uptake is mediated by a distinct, poorly characterised mechanism that appears to be essential for the intracellular parasite. Here, we examined infected cell Ca ++ uptake with a kinetic fluorescence assay and the virulent human pathogen, Plasmodium falciparum. Cell surface labelling with N-hydroxysulfosuccinimide esters revealed differing effects on transport into infected and uninfected cells, indicating that Ca ++ uptake at the infected cell surface is mediated by new or altered proteins at the host membrane. Conditional knockdown of PTEX, a translocon for export of parasite proteins into the host cell, significantly reduced infected cell Ca ++ permeability, suggesting involvement of parasite-encoded proteins trafficked to the host membrane. A high-throughput chemical screen identified the first Ca ++ transport inhibitors active against Plasmodium-infected cells. These novel chemical scaffolds inhibit both uptake and parasite growth; improved in vitro potency at reduced free [Ca ++ ] is consistent with parasite killing specifically via action on one or more Ca ++ transporters. These inhibitors should provide mechanistic insights into malaria parasite Ca ++ transport and may be starting points for new antimalarial drugs. © 2018 John Wiley & Sons Ltd.

Gimme shelter--the relative sensitivity of parasitic nematodes with direct and indirect life cycles to climate change.

PubMed

Molnár, Péter K; Dobson, Andrew P; Kutz, Susan J

2013-11-01

Climate change is expected to alter the dynamics of host-parasite systems globally. One key element in developing predictive models for these impacts is the life cycle of the parasite. It is, for example, commonly assumed that parasites with an indirect life cycle would be more sensitive to changing environmental conditions than parasites with a direct life cycle due to the greater chance that at least one of their obligate host species will go extinct. Here, we challenge this notion by contrasting parasitic nematodes with a direct life cycle against those with an indirect life cycle. Specifically, we suggest that behavioral thermoregulation by the intermediate host may buffer the larvae of indirectly transmitted parasites against temperature extremes, and hence climate warming. We term this the 'shelter effect'. Formalizing each life cycle in a comprehensive model reveals a fitness advantage for the direct life cycle over the indirect life cycle at low temperatures, but the shelter effect reverses this advantage at high temperatures. When examined for seasonal environments, the models suggest that climate warming may in some regions create a temporal niche in mid-summer that excludes parasites with a direct life cycle, but allows parasites with an indirect life cycle to persist. These patterns are amplified if parasite larvae are able to manipulate their intermediate host to increase ingestion probability by definite hosts. Furthermore, our results suggest that exploiting the benefits of host sheltering may have aided the evolution of indirect life cycles. Our modeling framework utilizes the Metabolic Theory of Ecology to synthesize the complexities of host behavioral thermoregulation and its impacts on various temperature-dependent parasite life history components in a single measure of fitness, R0 . It allows quantitative predictions of climate change impacts, and is easily generalized to many host-parasite systems. © 2013 John Wiley & Sons Ltd.

Understanding the interaction between an obligate hyperparasitic bacterium, Pasteuria penetrans and its obligate plant-parasitic nematode host, Meloidogyne spp.

PubMed

Davies, Keith G

2009-01-01

Pasteuria penetrans is an endospore-forming bacterium, which is a hyperparasite of root-knot nematodes Meloidogyne spp. that are economically important pests of a wide range of crops. The life cycle of the bacterium and nematode are described with emphasis on the bacterium's potential as a biocontrol agent. Two aspects that currently prohibit the commercial development of the bacterium as a biocontrol agent are the inability to culture it outside its host and its host specificity. Vegetative growth of the bacterium is possible in vitro; however, getting the vegetative stages of the bacterium to enter sporogenesis has been problematic. Insights from genomic survey sequences regarding the role of cation concentration and the phosphorylation of Spo0F have proved useful in inducing vegetative bacteria to sporulate. Similarly, genomic data have also proved useful in understanding the attachment of endospores to the cuticle of infective nematode juveniles, and a Velcro-like model of spore attachment is proposed that involves collagen-like fibres on the surface of the endospore interacting with mucins on the nematode cuticle. Ecological studies of the interactions between Daphnia and Pasteuria ramosa are examined and similarities are drawn between the co-evolution of virulence in the Daphnia system and that of plant-parasitic nematodes.

46 CFR 298.30 - Nature and content of Obligations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

46 CFR 298.30 - Nature and content of Obligations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

46 CFR 298.30 - Nature and content of Obligations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 8 2012-10-01 2012-10-01 false Nature and content of Obligations. 298.30 Section 298.30 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION VESSEL FINANCING ASSISTANCE OBLIGATION GUARANTEES Documentation § 298.30 Nature and content of Obligations. (a) Single page. An Obligation, in the...

46 CFR 298.30 - Nature and content of Obligations.

Code of Federal Regulations, 2014 CFR

2014-10-01

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46 CFR 298.30 - Nature and content of Obligations.

Code of Federal Regulations, 2013 CFR

2013-10-01

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7 CFR 400.167 - Limitations on Corporation's obligations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 6 2013-01-01 2013-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

7 CFR 400.167 - Limitations on Corporation's obligations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 6 2011-01-01 2011-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

7 CFR 400.167 - Limitations on Corporation's obligations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 6 2012-01-01 2012-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

7 CFR 400.167 - Limitations on Corporation's obligations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 6 2014-01-01 2014-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

7 CFR 400.167 - Limitations on Corporation's obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Limitations on Corporation's obligations. 400.167... INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement... Corporation's obligations. The Agreement will include the following among the limitations on the obligations...

Plant actin cytoskeleton re-modeling by plant parasitic nematodes.

PubMed

Engler, Janice de Almeida; Rodiuc, Natalia; Smertenko, Andrei; Abad, Pierre

2010-03-01

The cytoskeleton is an important component of the plant's defense mechanism against the attack of pathogenic organisms. Plants however, are defenseless against parasitic root-knot and cyst nematodes and respond to the invasion by the development of a special feeding site that supplies the parasite with nutrients required for the completion of its life cycle. Recent studies of nematode invasion under treatment with cytoskeletal drugs and in mutant plants where normal functions of the cytoskeleton have been affected, demonstrate the importance of the cytoskeleton in the establishment of a feeding site and successful nematode reproduction. It appears that in the case of microfilaments, nematodes hijack the intracellular machinery that regulates actin dynamics and modulate the organization and properties of the actin filament network. Intervening with this process reduces the nematode infection efficiency and inhibits its life cycle. This discovery uncovers a new pathway that can be exploited for the protection of plants against nematodes.

NCI & Division Obligations

Cancer.gov

Displays obligations for grants, contracts, training fellowships, intramural research, and management and support, including the number of grant awards, funding amounts, and percent of the total NCI budget.

31 CFR 1024.311 - Filing obligations.

Code of Federal Regulations, 2011 CFR

2011-07-01

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Changes to cholesterol trafficking in macrophages by Leishmania parasites infection.

PubMed

Semini, Geo; Paape, Daniel; Paterou, Athina; Schroeder, Juliane; Barrios-Llerena, Martin; Aebischer, Toni

2017-08-01

Leishmania spp. are protozoan parasites that are transmitted by sandfly vectors during blood sucking to vertebrate hosts and cause a spectrum of diseases called leishmaniases. It has been demonstrated that host cholesterol plays an important role during Leishmania infection. Nevertheless, little is known about the intracellular distribution of this lipid early after internalization of the parasite. Here, pulse-chase experiments with radiolabeled cholesteryl esterified to fatty acids bound to low-density lipoproteins indicated that retention of this source of cholesterol is increased in parasite-containing subcellular fractions, while uptake is unaffected. This is correlated with a reduction or absence of detectable NPC1 (Niemann-Pick disease, type C1), a protein responsible for cholesterol efflux from endocytic compartments, in the Leishmania mexicana habitat and infected cells. Filipin staining revealed a halo around parasites within parasitophorous vacuoles (PV) likely representing free cholesterol accumulation. Labeling of host cell membranous cholesterol by fluorescent cholesterol species before infection revealed that this pool is also trafficked to the PV but becomes incorporated into the parasites' membranes and seems not to contribute to the halo detected by filipin. This cholesterol sequestration happened early after infection and was functionally significant as it correlated with the upregulation of mRNA-encoding proteins required for cholesterol biosynthesis. Thus, sequestration of cholesterol by Leishmania amastigotes early after infection provides a basis to understand perturbation of cholesterol-dependent processes in macrophages that were shown previously by others to be necessary for their proper function in innate and adaptive immune responses. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Evaluation of two novel methods for assessing intracellular oxygen

NASA Astrophysics Data System (ADS)

Williams, Catrin F.; Kombrabail, M.; Vijayalakshmi, K.; White, Nick; Krishnamoorthy, G.; Lloyd, David

2012-08-01

The ability to resolve the spatio-temporal complexity of intracellular O2 distribution is the ‘Holy Grail’ of cellular physiology. In an effort to obtain a non-invasive approach of mapping intracellular O2 tensions, two methods of phosphorescent lifetime imaging microscopy were examined in the current study. These were picosecond time-resolved epiphosphorescence microscopy (single 0.5 µm focused spot) and two-photon confocal laser scanning microscopy with pinhole shifting. Both methods utilized nanoparticle-embedded Ru complex (45 nm diameter) as the phosphorescent probe, excited using pulsed outputs of Ti-sapphire Tsunami lasers (710-1050 nm). The former method used a 1 ps pulse width excitation beam with vertical polarization via a dichroic mirror (610 nm, XF43) and a 20× objective (NA 0.55, Nikon). Transmitted luminescence (1-2 × 104 counts s-1) was collected and time-correlated single photon counted decay times measured. Alternatively, an unmodified Zeiss LSM510 Confocal NLO microscope with 40× objective (NA 1.3) used successively shifted pinhole positions to collect image data from the lagging trail of the raster scan. Images obtained from two-photon excitation of a yeast (Schizosaccharomyces pombe) and a flagellate fish parasite (Spironucleus vortens), electroporated with Ru complex, indicated the intracellular location and magnitude of O2 gradients, thus confirming the feasibility of optical mapping under different external O2 concentrations. Both methods gave similar lifetimes for Ru complex phosphorescence under aerobic and anaerobic gas phases. Estimation of O2 tensions within individual fibroblasts (human dermal fibroblast (HDF)) and mammary adenocarcinoma (MCF-7) cells was possible using epiphosphorescence microscopy. MCF-7 cells showed lower intracellular O2 concentrations than HDF cells, possibly due to higher metabolic rates in the former. Future work should involve construction of higher resolution 3D maps of Ru coordinate complex lifetime

Parasitic egg rejection decisions of chalk-browed mockingbirds Mimus saturninus are independent of clutch composition.

PubMed

de la Colina, M A; Pompilio, L; Hauber, M E; Reboreda, J C; Mahler, B

2018-03-01

Obligate avian brood parasites lay their eggs in nests of other host species, which assume all the costs of parental care for the foreign eggs and chicks. The most common defensive response to parasitism is the rejection of foreign eggs by hosts. Different cognitive mechanisms and decision-making rules may guide both egg recognition and rejection behaviors. Classical optimization models generally assume that decisions are based on the absolute properties of the options (i.e., absolute valuation). Increasing evidence shows instead that hosts' rejection decisions also depend on the context in which options are presented (i.e., context-dependent valuation). Here we study whether the chalk-browed mockingbird's (Mimus saturninus) rejection of parasitic shiny cowbird (Molothrus bonariensis) eggs is a fixed behavior or varies with the context of the clutch. We tested three possible context-dependent mechanisms: (1) range effect, (2) habituation to variation, and (3) sensitization to variation. We found that mockingbird rejection of parasitic eggs does not change according to the characteristics of the other eggs in the nest. Thus, rejection decisions may exclusively depend on the objective characteristics of the eggs, meaning that the threshold of acceptance or rejection of a foreign egg is context-independent in this system.

43 CFR 10005.8 - Mitigation obligations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

43 CFR 10005.8 - Mitigation obligations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

43 CFR 10005.8 - Mitigation obligations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

43 CFR 10005.8 - Mitigation obligations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Mitigation obligations. 10005.8 Section... MITIGATION AND CONSERVATION COMMISSION POLICIES AND PROCEDURES FOR DEVELOPING AND IMPLEMENTING THE COMMISSION'S MITIGATION AND CONSERVATION PLAN § 10005.8 Mitigation obligations. While the Act authorizes the...

Comparative study of protective activities of Neospora caninum bradyzoite antigens, NcBAG1, NcBSR4, NcMAG1, and NcSAG4, in a mouse model of acute parasitic infection.

PubMed

Uchida, Masaki; Nagashima, Kotomi; Akatsuka, Yui; Murakami, Takashi; Ito, Akira; Imai, Soichi; Ike, Kazunori

2013-02-01

Neospora caninum is an obligate intracellular protozoan parasite that causes severe neuromuscular diseases, repeated abortion, stillbirth, and congenital infection in livestock and companion animals. The development of an effective vaccine against neosporosis in cattle is an important issue due to the significant worldwide economic impact of this disease. We evaluated the immunogenicity of four bradyzoite antigens, NcBAG1 (first described in this study), NcBSR4, NcMAG1, and NcSAG4, using an acute infection mouse model to determine synergistic effects with the tachyzoite antigen as a candidate for vaccine production. Mice were inoculated with the recombinant vaccines (r-)NcBAG1, rNcBSR4, rNcMAG1, rNcSAG4, or phosphate-buffered saline (PBS) (adjuvant control group) in an oil-in-water emulsion with bitter gourd extract, a Th1 immune stimulator, or PBS alone as the infection control group. Mice inoculated with each vaccine developed antigen-specific IgG1 and IgG2a antibodies and isolated splenocytes from mice produced high levels of interferon-γ when infected with the N. caninum tachyzoite. The mice inoculated with rNcBAG1, rNcMAG1, or rNcSAG4 developed slight to moderate clinical symptoms but did not succumb to infection. In contrast, rNcBSR4 and both control groups developed severe disease and some mice required euthanasia. The parasitic burden in the brain tissues of vaccinated mice was assessed by N. caninum-specific real-time PCR at 5 weeks after infection. The parasite load in rNcBAG1-, rNcMAG1-, and rNcSAG4-inoculated mice was significantly lower than that in adjuvant and infection control mice. Therefore, these antigens may be useful for the production of a N. caninum-specific vaccination protocol.

Obligate pollination mutualism in Breynia (Phyllanthaceae): further documentation of pollination mutualism involving Epicephala moths (Gracillariidae).

PubMed

Kawakita, Atsushi; Kato, Makoto

2004-09-01

This paper reports obligate seed-parasitic pollination mutualisms in Breynia vitis-idea and B. fruticosa (Phyllanthaceae). The genus Breynia is closely related to Glochidion and Gomphidium (a subgenus of Phyllanthus), in which pollination by species-specific, seed-parasitic Epicephala moths (Gracillariidae) have been previously reported. At night, female Epicephala moths carrying numerous pollen grains on their proboscises visited female flowers of B. vitis-idea, actively pollinated flowers, and each subsequently laid an egg. Examination of field-collected flowers indicated that pollinated flowers of B. vitis-idea and B. fruticosa almost invariably had Epicephala eggs, suggesting that these moths are the primary pollinators of the two species. Single Epicephala larvae consumed a fraction of seeds within developing fruit in B. vitis-idea and all seeds in B. fruticosa. However, some of the fruits were left untouched, and many of these had indication of moth oviposition, suggesting that egg/larval mortality of Epicephala moths is an important factor assuring seed set in these plants. The overall similarity of the specialized floral structure among Breynia species may indicate that this pollination system is fairly widespread within the genus.

Multiple Avirulence Paralogues in Cereal Powdery Mildew Fungi May Contribute to Parasite Fitness and Defeat of Plant Resistance

PubMed Central

Ridout, Christopher J.; Skamnioti, Pari; Porritt, Oliver; Sacristan, Soledad; Jones, Jonathan D.G.; Brown, James K.M.

2006-01-01

Powdery mildews, obligate biotrophic fungal parasites on a wide range of important crops, can be controlled by plant resistance (R) genes, but these are rapidly overcome by parasite mutants evading recognition. It is unknown how this rapid evolution occurs without apparent loss of parasite fitness. R proteins recognize avirulence (AVR) molecules from parasites in a gene-for-gene manner and trigger defense responses. We identify AVRa10 and AVRk1 of barley powdery mildew fungus, Blumeria graminis f sp hordei (Bgh), and show that they induce both cell death and inaccessibility when transiently expressed in Mla10 and Mlk1 barley (Hordeum vulgare) varieties, respectively. In contrast with other reported fungal AVR genes, AVRa10 and AVRk1 encode proteins that lack secretion signal peptides and enhance infection success on susceptible host plant cells. AVRa10 and AVRk1 belong to a large family with >30 paralogues in the genome of Bgh, and homologous sequences are present in other formae speciales of the fungus infecting other grasses. Our findings imply that the mildew fungus has a repertoire of AVR genes, which may function as effectors and contribute to parasite virulence. Multiple copies of related but distinct AVR effector paralogues might enable populations of Bgh to rapidly overcome host R genes while maintaining virulence. PMID:16905653

24 CFR 891.755 - Obligations of the family.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Obligations of the family. 891.755... the Elderly and Persons with Disabilities Section 202 Projects for the Nonelderly Handicapped Families and Individuals-Section 162 Assistance § 891.755 Obligations of the family. The obligations of the...

24 CFR 891.755 - Obligations of the family.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Obligations of the family. 891.755... the Elderly and Persons with Disabilities Section 202 Projects for the Nonelderly Handicapped Families and Individuals-Section 162 Assistance § 891.755 Obligations of the family. The obligations of the...

31 CFR 1026.311 - Filing obligations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... INTRODUCING BROKERS IN COMMODITIES Reports Required To Be Made by Futures Commission Merchants and Introducing Brokers in Commodities § 1026.311 Filing obligations. Refer to § 1010.311 of this chapter for reports of transactions in currency filing obligations for futures commission merchants and introducing brokers in...

24 CFR 891.615 - Obligations of the family.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Obligations of the family. 891.615 Section 891.615 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... 8 Assistance § 891.615 Obligations of the family. The obligations of the family are provided in...

24 CFR 891.615 - Obligations of the family.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Obligations of the family. 891.615 Section 891.615 Housing and Urban Development Regulations Relating to Housing and Urban Development... 8 Assistance § 891.615 Obligations of the family. The obligations of the family are provided in...

12 CFR 997.5 - Termination of the obligation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Termination of the obligation. 997.5 Section 997.5 Banks and Banking FEDERAL HOUSING FINANCE BOARD NON-BANK SYSTEM ENTITIES RESOLUTION FUNDING CORPORATION OBLIGATIONS OF THE BANKS § 997.5 Termination of the obligation. (a) Generally. The Banks...

24 CFR 213.266a - Insurance fund obligations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Insurance fund obligations. 213... Insurance fund obligations. A mortgage endorsed for insurance under section 213 of the Act shall be the obligation either of the Cooperative Management Housing Insurance Fund or of the General Insurance Fund. The...

Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease

PubMed Central

Haas, Laura T.; Salazar, Santiago V.; Kostylev, Mikhail A.; Um, Ji Won; Kaufman, Adam C.

2016-01-01

Alzheimer’s disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer’s disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer’s disease transgenes or by human Alzheimer’s disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp–Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer’s disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer’s disease pathogenesis, and the complex is a potential target for disease-modifying intervention. PMID:26667279

The Leishmania major BBSome subunit BBS1 is essential for parasite virulence in the mammalian host

PubMed Central

Price, Helen P; Paape, Daniel; Hodgkinson, Michael R; Farrant, Katie; Doehl, Johannes; Stark, Meg; Smith, Deborah F

2013-01-01

Summary Bardet–Biedl syndrome (BBS) is a human genetic disorder with a spectrum of symptoms caused by primary cilium dysfunction. The disease is caused by mutations in one of at least 17 identified genes, of which seven encode subunits of the BBSome, a protein complex required for specific trafficking events to and from the primary cilium. The molecular mechanisms associated with BBSome function remain to be fully elucidated. Here, we generated null and complemented mutants of the BBSome subunit BBS1 in the protozoan parasite, Leishmania. In the absence of BBS1, extracellular parasites have no apparent defects in growth, flagellum assembly, motility or differentiation in vitro but there is accumulation of vacuole-like structures close to the flagellar pocket. Infectivity of these parasites for macrophages in vitro is reduced compared with wild-type controls but the null parasites retain the ability to differentiate to the intracellular amastigote stage. However, infectivity of BBS1 null parasites is severely compromised in a BALB/c mouse footpad model. We hypothesize that the absence of BBS1 in Leishmania leads to defects in specific trafficking events that affect parasite persistence in the host. This is the first report of an association between the BBSome complex and pathogen infectivity. PMID:23998526

Enhanced innate immune responses in a brood parasitic cowbird species: degranulation and oxidative burst

USGS Publications Warehouse

Hahn, D. Caldwell; Summers, Scott G.; Genovese, Kenneth J.; He, Haiqi; Kogut, Michael H.

2013-01-01

We examined the relative effectiveness of two innate immune responses in two species of New World blackbirds (Passeriformes, Icteridae) that differ in resistance to West Nile virus (WNV). We measured degranulation and oxidative burst, two fundamental components of phagocytosis, and we predicted that the functional effectiveness of these innate immune responses would correspond to the species' relative resistance to WNV. The brown-headed cowbird (Molothrus ater), an obligate brood parasite, had previously shown greater resistance to infection with WNV, lower viremia and faster recovery when infected, and lower subsequent antibody titers than the red-winged blackbird (Agelaius phoeniceus), a close relative that is not a brood parasite. We found that cowbird leukocytes were significantly more functionally efficient than those of the blackbird leukocytes and 50% more effective at killing the challenge bacteria. These results suggest that further examination of innate immunity in the cowbird may provide insight into adaptations that underlie its greater resistance to WNV. These results support an eco-immunological interpretation that species like the cowbird, which inhabit ecological niches with heightened exposure to parasites, experience evolutionary selection for more effective immune responses.

47 CFR 27.1239 - Reimbursement obligation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Reimbursement obligation. 27.1239 Section 27... Policies Governing the Transition of the 2500-2690 Mhz Band for Brs and Ebs § 27.1239 Reimbursement obligation. (a) A proponent may request reimbursement from BRS licensees and lessees, EBS lessees, and...

Microsporidia infection impacts the host cell's cycle and reduces host cell apoptosis

PubMed Central

Higes, Mariano; Sagastume, Soledad; Juarranz, Ángeles; Dias-Almeida, Joyce; Budge, Giles E.; Meana, Aránzazu; Boonham, Neil

2017-01-01

Intracellular parasites can alter the cellular machinery of host cells to create a safe haven for their survival. In this regard, microsporidia are obligate intracellular fungal parasites with extremely reduced genomes and hence, they are strongly dependent on their host for energy and resources. To date, there are few studies into host cell manipulation by microsporidia, most of which have focused on morphological aspects. The microsporidia Nosema apis and Nosema ceranae are worldwide parasites of honey bees, infecting their ventricular epithelial cells. In this work, quantitative gene expression and histology were studied to investigate how these two parasites manipulate their host’s cells at the molecular level. Both these microsporidia provoke infection-induced regulation of genes involved in apoptosis and the cell cycle. The up-regulation of buffy (which encodes a pro-survival protein) and BIRC5 (belonging to the Inhibitor Apoptosis protein family) was observed after infection, shedding light on the pathways that these pathogens use to inhibit host cell apoptosis. Curiously, different routes related to cell cycle were modified after infection by each microsporidia. In the case of N. apis, cyclin B1, dacapo and E2F2 were up-regulated, whereas only cyclin E was up-regulated by N. ceranae, in both cases promoting the G1/S phase transition. This is the first report describing molecular pathways related to parasite-host interactions that are probably intended to ensure the parasite’s survival within the cell. PMID:28152065

Infection with parasitic nematodes confounds vaccination efficacy

PubMed Central

Urban, Joseph F.; Steenhard, Nina R.; Solano-Aguilar, Gloria I.; Dawson, Harry D.; Iweala, Onyinye I.; Nagler, Cathryn R.; Noland, Gregory S.; Kumar, Nirbhay; Anthony, Robert M.; Shea-Donohue, Terez; Weinstock, Joel; Gause, William C.

2007-01-01

T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-γ, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a

26 CFR 2.1-20 - Obligation of deposits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Obligation of deposits. 2.1-20 Section 2.1-20...) MARITIME CONSTRUCTION RESERVE FUND § 2.1-20 Obligation of deposits. (a) Time for obligation. Within three years from the date of any deposit in a construction reserve fund, unless extension is granted as...

Toxoplasma exports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression.

PubMed

Bougdour, Alexandre; Tardieux, Isabelle; Hakimi, Mohamed-Ali

2014-03-01

Toxoplasma gondii is the most widespread apicomplexan parasite and occupies a large spectrum of niches by infecting virtually any warm-blooded animals. As an obligate intracellular parasite, Toxoplasma has evolved a repertoire of strategies to fine-tune the cellular environment in an optimal way to promote growth and persistence in host tissues hence increasing the chance to be transmitted to new hosts. Short and long-term intracellular survival is associated with Toxoplasma ability to both evade the host deleterious immune defences and to stimulate a beneficial immune balance by governing host cell gene expression. It is only recently that parasite proteins responsible for driving these transcriptional changes have been identified. While proteins contained in the apical secretory Rhoptry organelle have already been identified as bona fide secreted effectors that divert host signalling pathways, recent findings revealed that dense granule proteins should be added to the growing list of effectors as they reach the host cell cytoplasm and nucleus and target various host cell pathways in the course of cell infection. Herein, we emphasize on a novel subfamily of dense granule residentproteins, exemplified with the GRA16 and GRA24 members we recently discovered as both are exported beyond the vacuole-containing parasites and reach the host cell nucleus to reshape the host genome expression. © 2013 John Wiley & Sons Ltd.

Standard of care, institutional obligations, and distributive justice.

PubMed

MacKay, Douglas

2015-05-01

The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies - agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

5 CFR 2635.809 - Just financial obligations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... obligations. Employees shall satisfy in good faith their obligations as citizens, including all just financial... employee or reduced to judgment by a court. In good faith means an honest intention to fulfill any just...

5 CFR 2635.809 - Just financial obligations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... obligations. Employees shall satisfy in good faith their obligations as citizens, including all just financial... employee or reduced to judgment by a court. In good faith means an honest intention to fulfill any just...

5 CFR 2635.809 - Just financial obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... obligations. Employees shall satisfy in good faith their obligations as citizens, including all just financial... employee or reduced to judgment by a court. In good faith means an honest intention to fulfill any just...

Social categories as markers of intrinsic interpersonal obligations.

PubMed

Rhodes, Marjorie; Chalik, Lisa

2013-06-01

Social categorization is an early-developing feature of human social cognition, yet the role that social categories play in children's understanding of and predictions about human behavior has been unclear. In the studies reported here, we tested whether a foundational functional role of social categories is to mark people as intrinsically obligated to one another (e.g., obligated to protect rather than harm). In three studies, children (aged 3-9, N = 124) viewed only within-category harm as violating intrinsic obligations; in contrast, they viewed between-category harm as violating extrinsic obligations defined by explicit rules. These data indicate that children view social categories as marking patterns of intrinsic interpersonal obligations, suggesting that a key function of social categories is to support inferences about how people will relate to members of their own and other groups.

Filial Obligation and Marital Satisfaction in Middle-aged Couples

PubMed Central

Seidel, Amber J.; Birditt, Kira S.; Zarit, Steven H.; Fingerman, Karen L.

2017-01-01

Abstract Purpose of the Study: Although prior research suggests that high filial obligation has an adverse impact on psychological well-being, little is known about the implications of these beliefs for marital quality during midlife. Therefore, the purpose of this study was to examine dyadic associations between middle-aged husbands’ and wives’ filial obligation beliefs and their marital satisfaction. Design and Methods: Using a sample of 132 middle-aged husbands (M = 51.45 years) and wives (M = 49.75 years) drawn from Wave 1 of the Family Exchanges Study, we tested actor–partner interdependence models to determine associations between husbands’ and wives’ filial obligation beliefs and marital satisfaction in both spouses. We also examined associations between spousal dissimilarity in filial obligation and marital satisfaction. Results: Wives’ greater filial obligation was associated with their own lower marital satisfaction. Conversely, husbands’ greater filial obligation was associated with their own higher marital satisfaction. Greater spousal dissimilarity in filial obligation was associated with lower levels of marital satisfaction for husbands but not for wives. Implications: Given that support provided to aging parents most often occurs within the context of marriage, findings highlight the importance of examining dyadic associations between filial obligation beliefs and marital quality among middle-aged couples. PMID:26613745

Is there a moral obligation not to infect others?

PubMed

Harris, J; Holm, S

1995-11-04

The emergence of HIV infection and AIDS has refocused concern on the obligations surrounding the carrying and transmission of communicable diseases. This article asks three related questions: Is there a general duty not to spread contagion? Are there special obligations not to communicate disease in the workplace? And does the mode of transmission of the disease affect the ethics of transmission and, if so, how and to what extent? There seems to be a strong prima facie obligation not to harm others by making them ill where this is avoidable, and this obligation not to communicate disease applies as much to relatively trivial diseases like the common cold as it does to HIV disease. The reasonableness of expecting people to live up to this obligation, however, depends on society reciprocating the obligation in the form of providing protection and compensation.

The role of septins in infections with vacuole-dwelling intracellular bacteria.

PubMed

Häcker, Georg

2017-07-29

Septins are a relatively little understood group of GTPases that form large assemblies in cells from all eukaryotes other than plants. Septins were first identified in cell division but have also been implicated in microbial infections. Septins often associate with cytoskeletal proteins - most often described for filamentous (F-) actin - and are considered cytoskeletal components themselves. Septins have increasingly been found to partake in processes that are linked to intracellular membranes, from mitochondria to phagosomes, and evidence is accumulating that septins specifically bind to membranes. Since a number of microorganisms have specialized to live and grow inside membranous vacuoles in the cytosol of mammalian cells, this membrane-association of septins suggests that septins may also be involved in the membranous, vacuolar structures that develop around these microbes. However, data are limited on this issue: septins have been identified by proteome analysis on some microbe-bearing vacuoles, but more extensive experimental data are only available for infections with the obligate intracellular bacterium Chlamydia trachomatis. In this review article I will discuss the available data and speculate about the mechanisms of recruitment and potential functions of septins for vacuole-dwelling microorganisms, which may be peculiar to Chlamydia or may pertain more generally to this class of microbes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Back to basics: a revealing secondary reduction of the mitochondrial protein import pathway in diverse intracellular parasites.

PubMed

Heinz, Eva; Lithgow, Trevor

2013-02-01

Mitochondria are present in all eukaryotes, but remodeling of their metabolic contribution has in some cases left them almost unrecognizable and they are referred to as mitochondria-like organelles, hydrogenosomes or, in the case where evolution has led to a great deal of simplification, as mitosomes. Mitochondria rely on the import of proteins encoded in the nucleus and the protein import machinery has been investigated in detail in yeast: several sophisticated molecular machines act in concert to import substrate proteins across the outer mitochondrial membrane and deliver them to a precise sub-mitochondrial compartment. Because these machines are so sophisticated, it has been a major challenge to conceptualize the first phase of their evolution. Here we review recent studies on the protein import pathway in parasitic species that have mitosomes: in the course of their evolution for highly specialized niches these parasites, particularly Cryptosporidia and Microsporidia, have secondarily lost numerous protein functions, in accordance with the evolution of their genomes towards a minimal size. Microsporidia are related to fungi, Cryptosporidia are apicomplexans and kin to the malaria parasite Plasmodium; and this great phylogenetic distance makes it remarkable that Microsporidia and Cryptosporidia have independently evolved skeletal protein import pathways that are almost identical. We suggest that the skeletal pathway reflects the protein import machinery of the first eukaryotes, and defines the essential roles of the core elements of the mitochondrial protein import machinery. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

Silencing cytokeratin 18 gene inhibits intracellular replication of Trypanosoma cruzi in HeLa cells but not binding and invasion of trypanosomes.

PubMed

Claser, Carla; Curcio, Marli; de Mello, Samanta M; Silveira, Eduardo V; Monteiro, Hugo P; Rodrigues, Mauricio M

2008-12-17

As an obligatory intracellular parasite, Trypanosoma cruzi, the etiological agent of Chagas' disease, must invade and multiply within mammalian cells. Cytokeratin 18 (CK18) is among the host molecules that have been suggested as a mediator of important events during T. cruzi-host cell interaction. Based on that possibility, we addressed whether RNA interference (RNAi)-mediated down regulation of the CK18 gene could interfere with the parasite life cycle in vitro. HeLa cells transiently transfected with CK18-RNAi had negligible levels of CK18 transcripts, and significantly reduced levels of CK18 protein expression as determined by immunoblotting or immunofluorescence. CK18 negative or positive HeLa cells were invaded equally as well by trypomastigotes of different T. cruzi strains. Also, in CK18 negative or positive cells, parasites recruited host cells lysosomes and escaped from the parasitophorous vacuole equally as well. After that, the growth of amastigotes of the Y or CL-Brener strains, was drastically arrested in CK18 RNAi-treated cells. After 48 hours, the number of amastigotes was several times lower in CK18 RNAi-treated cells when compared to control cells. Simultaneous staining of parasites and CK18 showed that in HeLa cells infected with the Y strain both co-localize. Although the amastigote surface protein-2 contains the domain VTVXNVFLYNR previously described to bind to CK18, in several attempts, we failed to detect binding of a recombinant protein to CK-18. The study demonstrates that silencing CK18 by transient RNAi, inhibits intracellular multiplication of the Y and CL strain of T. cruzi in HeLa cells, but not trypanosome binding and invasion.

Silencing cytokeratin 18 gene inhibits intracellular replication of Trypanosoma cruzi in HeLa cells but not binding and invasion of trypanosomes

PubMed Central

Claser, Carla; Curcio, Marli; de Mello, Samanta M; Silveira, Eduardo V; Monteiro, Hugo P; Rodrigues, Mauricio M

2008-01-01

Background As an obligatory intracellular parasite, Trypanosoma cruzi, the etiological agent of Chagas' disease, must invade and multiply within mammalian cells. Cytokeratin 18 (CK18) is among the host molecules that have been suggested as a mediator of important events during T. cruzi-host cell interaction. Based on that possibility, we addressed whether RNA interference (RNAi)-mediated down regulation of the CK18 gene could interfere with the parasite life cycle in vitro. HeLa cells transiently transfected with CK18-RNAi had negligible levels of CK18 transcripts, and significantly reduced levels of CK18 protein expression as determined by immunoblotting or immunofluorescence. Results CK18 negative or positive HeLa cells were invaded equally as well by trypomastigotes of different T. cruzi strains. Also, in CK18 negative or positive cells, parasites recruited host cells lysosomes and escaped from the parasitophorous vacuole equally as well. After that, the growth of amastigotes of the Y or CL-Brener strains, was drastically arrested in CK18 RNAi-treated cells. After 48 hours, the number of amastigotes was several times lower in CK18 RNAi-treated cells when compared to control cells. Simultaneous staining of parasites and CK18 showed that in HeLa cells infected with the Y strain both co-localize. Although the amastigote surface protein-2 contains the domain VTVXNVFLYNR previously described to bind to CK18, in several attempts, we failed to detect binding of a recombinant protein to CK-18. Conclusion The study demonstrates that silencing CK18 by transient RNAi, inhibits intracellular multiplication of the Y and CL strain of T. cruzi in HeLa cells, but not trypanosome binding and invasion. PMID:19087356

Visceral leishmaniasis with Roth spots

PubMed Central

Meena, Jagdish; Juneja, Monica; Mishra, Devendra; Vats, Pallavi; Pawaria, Arti

2014-01-01

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. The protozoa is obliged intracellularly and causes a wide spectrum of clinical syndromes: VL (‘kala azar’), cutaneous leishmaniasis and mucocutaneous leishmaniasis (espundia). Kala azar is the most aggressive form and if untreated causes high mortality. Here, we describe a case of VL that presented to us with high-grade fever and found to have Roth spots that were resolved after 15 days of therapy. PMID:25988048

Population dynamics of obligate cooperators

PubMed Central

Courchamp, F.; Grenfell, B.; Clutton-Brock, T.

1999-01-01

Obligate cooperative breeding species demonstrate a high rate of group extinction, which may be due to the existence of a critical number of helpers below which the group cannot subsist. Through a simple model, we study the population dynamics of obligate cooperative breeding species, taking into account the existence of a lower threshold below which the instantaneous growth rate becomes negative. The model successively incorporates (i) a distinction between species that need helpers for reproduction, survival or both, (ii) the existence of a migration rate accounting for dispersal, and (iii) stochastic mortality to simulate the effects of random catastrophic events. Our results suggest that the need for a minimum number of helpers increases the risk of extinction for obligate cooperative breeding species. The constraint imposed by this threshold is higher when helpers are needed for reproduction only or for both reproduction and survival. By driving them below this lower threshold, stochastic mortality of lower amplitude and/or lower frequency than for non-cooperative breeders may be sufficient to cause the extinction of obligate cooperative breeding groups. Migration may have a buffering effect only for groups where immigration is higher than emigration; otherwise (when immigrants from nearby groups are not available) it lowers the difference between actual group size and critical threshold, thereby constituting a higher constraint.

Whistleblowing and the bioethicist's public obligations.

PubMed

MacDougall, D Robert

2014-10-01

Bioethicists are sometimes thought to have heightened obligations by virtue of the fact that their professional role addresses ethics or morals. For this reason it has been argued that bioethicists ought to "whistleblow"--that is, publicly expose the wrongful or potentially harmful activities of their employer--more often than do other kinds of employees. This article argues that bioethicists do indeed have a heightened obligation to whistleblow, but not because bioethicists have heightened moral obligations in general. Rather, the special duties of bioethicists to act as whistleblowers are best understood by examining the nature of the ethical dilemma typically encountered by private employees and showing why bioethicists do not encounter this dilemma in the same way. Whistleblowing is usually understood as a moral dilemma involving conflicting duties to two parties: the public and a private employer. However, this article argues that this way of understanding whistleblowing has the implication that professions whose members identify their employer as the public-such as government employees or public servants--cannot consider whistleblowing a moral dilemma, because obligations are ultimately owed to only one party: the public. The article contends that bioethicists--even when privately employed--are similar to government employees in the sense that they do not have obligations to defer to the judgments of those with private interests. Consequently, bioethicists may be considered to have a special duty to whistleblow, although for different reasons than those usually cited.

Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion.

PubMed

Srinivasan, Prakash; Yasgar, Adam; Luci, Diane K; Beatty, Wandy L; Hu, Xin; Andersen, John; Narum, David L; Moch, J Kathleen; Sun, Hongmao; Haynes, J David; Maloney, David J; Jadhav, Ajit; Simeonov, Anton; Miller, Louis H

2013-01-01

Plasmodium falciparum resistance to artemisinin derivatives, the first-line antimalarial drug, drives the search for new classes of chemotherapeutic agents. Current discovery is primarily directed against the intracellular forms of the parasite. However, late schizont-infected red blood cells (RBCs) may still rupture and cause disease by sequestration; consequently targeting invasion may reduce disease severity. Merozoite invasion of RBCs requires interaction between two parasite proteins AMA1 and RON2. Here we identify the first inhibitor of this interaction that also blocks merozoite invasion in genetically distinct parasites by screening a library of over 21,000 compounds. We demonstrate that this inhibition is mediated by the small molecule binding to AMA1 and blocking the formation of AMA1-RON complex. Electron microscopy confirms that the inhibitor prevents junction formation, a critical step in invasion that results from AMA1-RON2 binding. This study uncovers a strategy that will allow for highly effective combination therapies alongside existing antimalarial drugs.

Plant parasitic nematode effectors target host defense and nuclear functions to establish feeding cells.

PubMed

Quentin, Michaëel; Abad, Pierre; Favery, Bruno

2013-01-01

Plant parasitic nematodes are microscopic worms, the most damaging species of which have adopted a sedentary lifestyle within their hosts. These obligate endoparasites have a biotrophic relationship with plants, in which they induce the differentiation of root cells into hypertrophied, multinucleate feeding cells (FCs). Effectors synthesized in the esophageal glands of the nematode are injected into the plant cells via the syringe-like stylet and play a key role in manipulating the host machinery. The establishment of specialized FCs requires these effectors to modulate many aspects of plant cell morphogenesis and physiology, including defense responses. This cell reprogramming requires changes to host nuclear processes. Some proteins encoded by parasitism genes target host nuclei. Several of these proteins were immunolocalized within FC nuclei or shown to interact with host nuclear proteins. Comparative genomics and functional analyses are gradually revealing the roles of nematode effectors. We describe here these effectors and their hypothesized roles in the unique feeding behavior of these pests.

Paternity-parasitism trade-offs: a model and test of host-parasite cooperation in an avian conspecific brood parasite.

PubMed

Lyon, Bruce E; Hochachka, Wesley M; Eadie, John M

2002-06-01

Efforts to evaluate the evolutionary and ecological dynamics of conspecific brood parasitism in birds and other animals have focused on the fitness costs of parasitism to hosts and fitness benefits to parasites. However, it has been speculated recently that, in species with biparental care, host males might cooperate with parasitic females by allowing access to the host nest in exchange for copulations. We develop a cost-benefit model to explore the conditions under which such host-parasite cooperation might occur. When the brood parasite does not have a nest of her own, the only benefit to the host male is siring some of the parasitic eggs (quasi-parasitism). Cooperation with the parasite is favored when the ratio of host male paternity of his own eggs relative to his paternity of parasitic eggs exceeds the cost of parasitism. When the brood parasite has a nest of her own, a host male can gain additional, potentially more important benefits by siring the high-value, low-cost eggs laid by the parasite in her own nest. Under these conditions, host males should be even more likely to accept parasitic eggs in return for copulations with the parasitic female. We tested these predictions for American coots (Fulica americana), a species with a high frequency of conspecific brood parasitism. Multilocus DNA profiling indicated that host males did not sire any of the parasitic eggs laid in host nests, nor did they sire eggs laid by the parasite in her own nest. We used field estimates of the model parameters from a four-year study of coots to predict the minimum levels of paternity required for the costs of parasitism to be offset by the benefits of mating with brood parasites. Observed levels of paternity were significantly lower than those predicted under a variety of assumptions, and we reject the hypothesis that host males cooperated with parasitic females. Our model clarifies the specific costs and benefits that influence host-parasite cooperation and, more generally

Chlamydia pneumoniae exploits adipocyte lipid chaperone FABP4 to facilitate fat mobilization and intracellular growth in murine adipocytes.

PubMed

Walenna, Nirwana Fitriani; Kurihara, Yusuke; Chou, Bin; Ishii, Kazunari; Soejima, Toshinori; Itoh, Ryota; Shimizu, Akinori; Ichinohe, Takeshi; Hiromatsu, Kenji

2018-01-01

Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via β-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma cruzi by Chemical Library Screening

PubMed Central

Bettiol, Esther; Samanovic, Marie; Murkin, Andrew S.; Raper, Jayne; Buckner, Frederick; Rodriguez, Ana

2009-01-01

The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing β-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC50: 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the anti–T. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC50 values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis. PMID:19238193

Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening.

PubMed

Bettiol, Esther; Samanovic, Marie; Murkin, Andrew S; Raper, Jayne; Buckner, Frederick; Rodriguez, Ana

2009-01-01

The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing beta-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC(50): 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the anti-T. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC(50) values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis.

Calcium Signaling throughout the Toxoplasma gondii Lytic Cycle

PubMed Central

Borges-Pereira, Lucas; Budu, Alexandre; McKnight, Ciara A.; Moore, Christina A.; Vella, Stephen A.; Hortua Triana, Miryam A.; Liu, Jing; Garcia, Celia R. S.; Pace, Douglas A.; Moreno, Silvia N. J.

2015-01-01

Toxoplasma gondii is an obligate intracellular parasite that invades host cells, creating a parasitophorous vacuole where it communicates with the host cell cytosol through the parasitophorous vacuole membrane. The lytic cycle of the parasite starts with its exit from the host cell followed by gliding motility, conoid extrusion, attachment, and invasion of another host cell. Here, we report that Ca2+ oscillations occur in the cytosol of the parasite during egress, gliding, and invasion, which are critical steps of the lytic cycle. Extracellular Ca2+ enhances each one of these processes. We used tachyzoite clonal lines expressing genetically encoded calcium indicators combined with host cells expressing transiently expressed calcium indicators of different colors, and we measured Ca2+ changes in both parasites and host simultaneously during egress. We demonstrated a link between cytosolic Ca2+ oscillations in the host and in the parasite. Our approach also allowed us to measure two new features of motile parasites, which were enhanced by Ca2+ influx. This is the first study showing, in real time, Ca2+ signals preceding egress and their direct link with motility, an essential virulence trait. PMID:26374900

Patients' ethical obligation for their health.

PubMed Central

Sider, R C; Clements, C D

1984-01-01

In contemporary medical ethics health is rarely acknowledged to be an ethical obligation. This oversight is due to the preoccupation of most bioethicists with a rationalist, contract model for ethics in which moral obligation is limited to truth-telling and promise-keeping. Such an ethics is poorly suited to medicine because it fails to appreciate that medicine's basis as a moral enterprise is oriented towards health values. A naturalistic model for medical ethics is proposed which builds upon biological and medical values. This perspective clarifies ethical obligations to ourselves and to others for life and health. It provides a normative framework for the doctor-patient relationship within which to formulate medical advice and by which to evaluate patient choice. PMID:6502640

24 CFR 266.415 - Mortgage lien and other obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... determine, that all contractual obligations in connection with the mortgage transaction, including the... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Mortgage lien and other obligations... Mortgage and Closing Requirements; HUD Endorsement § 266.415 Mortgage lien and other obligations. (a) Liens...

Is there a moral obligation not to infect others?

PubMed Central

Harris, J.; Holm, S.

1995-01-01

The emergence of HIV infection and AIDS has refocused concern on the obligations surrounding the carrying and transmission of communicable diseases. This article asks three related questions: Is there a general duty not to spread contagion? Are there special obligations not to communicate disease in the workplace? And does the mode of transmission of the disease affect the ethics of transmission and, if so, how and to what extent? There seems to be a strong prima facie obligation not to harm others by making them ill where this is avoidable, and this obligation not to communicate disease applies as much to relatively trivial diseases like the common cold as it does to HIV disease. The reasonableness of expecting people to live up to this obligation, however, depends on society reciprocating the obligation in the form of providing protection and compensation. Images p1216-a p1216-b p1217-a PMID:7488907

Molecular cloning, organellar targeting and developmental expression of mitochondrial chaperone HSP60 in Toxoplasma gondii.

PubMed

Toursel, C; Dzierszinski, F; Bernigaud, A; Mortuaire, M; Tomavo, S

2000-12-01

The obligate intracellular protozoan parasite Toxoplasma gondii has a single tubular mitochondrion. During infection, it recruits the host cell's mitochondria abutting to the intracellular vacuole, that contains the parasites. The respective contribution of host and parasitic mitochondria in the intracellular growth of T. gondii remains unknown. Heat shock protein, HSP60 has been reported in all eukaryotes examined, as an essential chaperone required for the folding and multimeric complex assembly of mitochondrial proteins. Here, we report the isolation and molecular characterization of two cDNAs corresponding to a single T. gondii gene coding for HSP60. Using a model fusion protein, preHSP60-chloramphenicol acetyl transferase (CAT), we demonstrate that the classical 22 amino acid mitochondrial presequence and the adjacent 32 amino acids of the mature protein are both required for the in vivo import into T. gondii mitochondria. The T. gondii HSP60 gene composed of five introns and six exons is transcribed into two related but differently spliced transcripts. Whereas the two transcripts can be detected in both developmental stages within the intermediate host, their levels are significantly increased in bradyzoites when compared to tachyzoites. By immunoblot analysis, the predicted 60-kDa protien corresponding to HSP60 was detected in both tachyzoite and bradyzoite forms. Using immunofluorescence assays. the polyclonal antibodies specific to T. gondii HSP60 recognized the mitochondrion in tachyzoites, as expected. In contrast, these antibodies reacted against two unknown vesicular bodies which are distinct from the classical mitochondrial pattern in bradyzoites. Taken together. these expression patterns of mitochondrial chaperone HSP60 suggests stage-specific induction of the respiratory pathway in the protozoan parasite T. gondii.

Inability and Obligation in Moral Judgment

PubMed Central

Buckwalter, Wesley; Turri, John

2015-01-01

It is often thought that judgments about what we ought to do are limited by judgments about what we can do, or that “ought implies can.” We conducted eight experiments to test the link between a range of moral requirements and abilities in ordinary moral evaluations. Moral obligations were repeatedly attributed in tandem with inability, regardless of the type (Experiments 1–3), temporal duration (Experiment 5), or scope (Experiment 6) of inability. This pattern was consistently observed using a variety of moral vocabulary to probe moral judgments and was insensitive to different levels of seriousness for the consequences of inaction (Experiment 4). Judgments about moral obligation were no different for individuals who can or cannot perform physical actions, and these judgments differed from evaluations of a non-moral obligation (Experiment 7). Together these results demonstrate that commonsense morality rejects the “ought implies can” principle for moral requirements, and that judgments about moral obligation are made independently of considerations about ability. By contrast, judgments of blame were highly sensitive to considerations about ability (Experiment 8), which suggests that commonsense morality might accept a “blame implies can” principle. PMID:26296206

Interacting parasites

USGS Publications Warehouse

Lafferty, Kevin D.

2010-01-01

Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

47 CFR 211.7 - Obligation of carriers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

47 CFR 211.7 - Obligation of carriers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

47 CFR 211.7 - Obligation of carriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

47 CFR 211.7 - Obligation of carriers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

47 CFR 211.7 - Obligation of carriers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Obligation of carriers. 211.7 Section 211.7 Telecommunication OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND NATIONAL SECURITY COUNCIL EMERGENCY RESTORATION PRIORITY PROCEDURES FOR TELECOMMUNICATIONS SERVICES § 211.7 Obligation of carriers. (a) During the...

An Agar-Based Method for Plating Marine Protozoan Parasites of the Genus Perkinsus

PubMed Central

Cold, Emma R.; Freyria, Nastasia J.; Martínez Martínez, Joaquín; Fernández Robledo, José A.

2016-01-01

The genus Perkinsus includes protozoan parasites of mollusks responsible for losses in the aquaculture industry and hampering the recovery of natural shellfish beds worldwide, and they are a key taxon for understanding intracellular parasitism adaptations. The ability to propagate the parasite in liquid media, in the absence of the host, has been crucial for improving understanding of its biology; however, alternative techniques to grow the parasite are needed to explore other basic aspects of the Perkinsus spp. biology. We optimized a DME: Ham’s F12–5% FBS- containing solid agar medium for plating Perkinsus marinus. This solid medium supported trophozoite propagation both by binary fission and schizogony. Colonies were visible to the naked eye 17 days after plating. We tested the suitability of this method for several applications, including the following: 1) Subcloning P. marinus isolates: single discrete P. marinus colonies were obtained from DME: Ham’s F12–5% FBS– 0.75% agar plates, which could be further propagated in liquid medium; 2) Subcloning engineered Perkinsus mediterraneus MOE[MOE]: GFP by streaking cultures on plates; 3) Chemical susceptibility: Infusing the DME: Ham’s F12–5% FBS– 0.75% agar plates with triclosan resulted in inhibition of the parasite propagation in a dose-dependent manner. Altogether, our plating method has the potential for becoming a key tool for investigating diverse aspects of Perkinsus spp. biology, developing new molecular tools, and for biotechnological applications. PMID:27149378

An Agar-Based Method for Plating Marine Protozoan Parasites of the Genus Perkinsus.

PubMed

Cold, Emma R; Freyria, Nastasia J; Martínez Martínez, Joaquín; Fernández Robledo, José A

2016-01-01

The genus Perkinsus includes protozoan parasites of mollusks responsible for losses in the aquaculture industry and hampering the recovery of natural shellfish beds worldwide, and they are a key taxon for understanding intracellular parasitism adaptations. The ability to propagate the parasite in liquid media, in the absence of the host, has been crucial for improving understanding of its biology; however, alternative techniques to grow the parasite are needed to explore other basic aspects of the Perkinsus spp. biology. We optimized a DME: Ham's F12-5% FBS- containing solid agar medium for plating Perkinsus marinus. This solid medium supported trophozoite propagation both by binary fission and schizogony. Colonies were visible to the naked eye 17 days after plating. We tested the suitability of this method for several applications, including the following: 1) Subcloning P. marinus isolates: single discrete P. marinus colonies were obtained from DME: Ham's F12-5% FBS- 0.75% agar plates, which could be further propagated in liquid medium; 2) Subcloning engineered Perkinsus mediterraneus MOE[MOE]: GFP by streaking cultures on plates; 3) Chemical susceptibility: Infusing the DME: Ham's F12-5% FBS- 0.75% agar plates with triclosan resulted in inhibition of the parasite propagation in a dose-dependent manner. Altogether, our plating method has the potential for becoming a key tool for investigating diverse aspects of Perkinsus spp. biology, developing new molecular tools, and for biotechnological applications.

49 CFR 22.17 - Compliance with child support obligations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

49 CFR 22.17 - Compliance with child support obligations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

49 CFR 22.17 - Compliance with child support obligations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

49 CFR 22.17 - Compliance with child support obligations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

49 CFR 22.17 - Compliance with child support obligations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Compliance with child support obligations. 22.17...) Policies Applying to STLP Loans § 22.17 Compliance with child support obligations. Any holder of 50% or... than 60 days delinquent on any obligation to pay child support arising under: (a) An administrative...

Detection of parasitic plant suicide germination compounds using a high-throughput Arabidopsis HTL/KAI2 strigolactone perception system.

PubMed

Toh, Shigeo; Holbrook-Smith, Duncan; Stokes, Michael E; Tsuchiya, Yuichiro; McCourt, Peter

2014-08-14

Strigolactones are terpenoid-based plant hormones that act as communication signals within a plant, between plants and fungi, and between parasitic plants and their hosts. Here we show that an active enantiomer form of the strigolactone GR24, the germination stimulant karrikin, and a number of structurally related small molecules called cotylimides all bind the HTL/KAI2 α/β hydrolase in Arabidopsis. Strigolactones and cotylimides also promoted an interaction between HTL/KAI2 and the F-box protein MAX2 in yeast. Identification of this chemically dependent protein-protein interaction prompted the development of a yeast-based, high-throughput chemical screen for potential strigolactone mimics. Of the 40 lead compounds identified, three were found to have in planta strigolactone activity using Arabidopsis-based assays. More importantly, these three compounds were all found to stimulate suicide germination of the obligate parasitic plant Striga hermonthica. These results suggest that screening strategies involving yeast/Arabidopsis models may be useful in combating parasitic plant infestations. Copyright © 2014 Elsevier Ltd. All rights reserved.

A temporary social parasite of tropical plant-ants improves the fitness of a myrmecophyte

NASA Astrophysics Data System (ADS)

Dejean, Alain; Leroy, Céline; Corbara, Bruno; Céréghino, Régis; Roux, Olivier; Hérault, Bruno; Rossi, Vivien; Guerrero, Roberto J.; Delabie, Jacques H. C.; Orivel, Jérôme; Boulay, Raphaël

2010-10-01

Myrmecophytes offer plant-ants a nesting place in exchange for protection from their enemies, particularly defoliators. These obligate ant-plant mutualisms are common model systems for studying factors that allow horizontally transmitted mutualisms to persist since parasites of ant-myrmecophyte mutualisms exploit the rewards provided by host plants whilst providing no protection in return. In pioneer formations in French Guiana, Azteca alfari and Azteca ovaticeps are known to be mutualists of myrmecophytic Cecropia ( Cecropia ants). Here, we show that Azteca andreae, whose colonies build carton nests on myrmecophytic Cecropia, is not a parasite of Azteca- Cecropia mutualisms nor is it a temporary social parasite of A. alfari; it is, however, a temporary social parasite of A. ovaticeps. Contrarily to the two mutualistic Azteca species that are only occasional predators feeding mostly on hemipteran honeydew and food bodies provided by the host trees, A. andreae workers, which also attend hemipterans, do not exploit the food bodies. Rather, they employ an effective hunting technique where the leaf margins are fringed with ambushing workers, waiting for insects to alight. As a result, the host trees’ fitness is not affected as A. andreae colonies protect their foliage better than do mutualistic Azteca species resulting in greater fruit production. Yet, contrarily to mutualistic Azteca, when host tree development does not keep pace with colony growth, A. andreae workers forage on surrounding plants; the colonies can even move to a non- Cecropia tree.

7 CFR 1000.28 - Termination of obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... which the market administrator receives the handler's report of receipts and utilization on which such obligation is based, unless within such 2-year period, the market administrator notifies the handler in... producer(s) or such cooperative association, or if the obligation is payable to the market administrator...

10 CFR 611.112 - Termination of obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Termination of obligations. 611.112 Section 611.112 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY VEHICLES MANUFACTURER ASSISTANCE PROGRAM Direct Loan Program § 611.112 Termination of obligations. DOE, the Federal Financing Bank, and the...

5 CFR 2426.13 - Obligation to consult.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Obligation to consult. 2426.13 Section 2426.13 Administrative Personnel FEDERAL LABOR RELATIONS AUTHORITY, GENERAL COUNSEL OF THE FEDERAL... Regulations § 2426.13 Obligation to consult. (a) When a labor organization has been accorded consultation...

Legionella pneumophila mutants that are defective for iron acquisition and assimilation and intracellular infection.

PubMed Central

Pope, C D; O'Connell, W; Cianciotto, N P

1996-01-01

Legionella pneumophila, a parasite of macrophages and protozoa, requires iron for optimal extracellular and intracellular growth. However, its mechanisms of iron acquisition remain uncharacterized. Using mini-Tn10 mutagenesis, we isolated 17 unique L. pneumophila strains which appeared to be defective for iron acquisition and assimilation. Eleven of these mutants were both sensitive to the iron chelator ethylenediamine di(o-hydroxyphenylacetic acid) and resistant to streptonigrin, an antibiotic whose lethal effect requires high levels of intracellular iron. Six mutants were also defective for the infection of macrophage-like U937 cells. Although none were altered in entry, mutants generally exhibited prolonged lag phases and in some cases replicated at slower rates. Overall, the reduced recoveries of mutants, relative to that of the wild type, ranged from 3- to 1,000-fold. Strain NU216, the mutant displaying the most severe lag phase and the slowest rate of replication, was studied further. Importantly, within U937 cells, NU216 was approximately 100-fold more sensitive than the wild type was to treatment with the Fe3+ chelator deferoxamine, indicating that it is defective for intracellular iron acquisition and assimilation. Furthermore, this strain was unable to mediate any cytopathic effect and was impaired for infectivity of an amoebal host. Taken together, the isolation of these mutants offers genetic proof that iron acquisition and assimilation are critical for intracellular infection by L. pneumophila. PMID:8550218

18 CFR 346.3 - Asset retirement obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Asset retirement obligations. 346.3 Section 346.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... to the asset retirement obligations that are included in the book balances of all accounts reflected...

18 CFR 35.18 - Asset retirement obligations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

18 CFR 35.18 - Asset retirement obligations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

18 CFR 35.18 - Asset retirement obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

18 CFR 35.18 - Asset retirement obligations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

18 CFR 35.18 - Asset retirement obligations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Asset retirement obligations. 35.18 Section 35.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Other Filing Requirements § 35.18 Asset retirement obligations. (a) A public utility that files a rate...

26 CFR 1.454-1 - Obligations issued at discount.

Code of Federal Regulations, 2010 CFR

2010-04-01

... series E bond, at which time the stated redemption value was $674.60. A never elected under section 454(a... obligation, in which he retains his investment in a matured series E U.S. savings bond, or (iii) A nontransferable obligation (whether or not a current income obligation) of the United States for which a series E...

Osmoadaptative Strategy and Its Molecular Signature in Obligately Halophilic Heterotrophic Protists

PubMed Central

Harding, Tommy; Brown, Matthew W.; Simpson, Alastair G.B.; Roger, Andrew J.

2016-01-01

Halophilic microbes living in hypersaline environments must counteract the detrimental effects of low water activity and salt interference. Some halophilic prokaryotes equilibrate their intracellular osmotic strength with the extracellular milieu by importing inorganic solutes, mainly potassium. These “salt-in” organisms characteristically have proteins that are highly enriched with acidic and hydrophilic residues. In contrast, “salt-out” halophiles accumulate large amounts of organic solutes like amino acids, sugars and polyols, and lack a strong signature of halophilicity in the amino acid composition of cytoplasmic proteins. Studies to date have examined halophilic prokaryotes, yeasts, or algae, thus virtually nothing is known about the molecular adaptations of the other eukaryotic microbes, that is, heterotrophic protists (protozoa), that also thrive in hypersaline habitats. We conducted transcriptomic investigations to unravel the molecular adaptations of two obligately halophilic protists, Halocafeteria seosinensis and Pharyngomonas kirbyi. Their predicted cytoplasmic proteomes showed increased hydrophilicity compared with marine protists. Furthermore, analysis of reconstructed ancestral sequences suggested that, relative to mesophiles, proteins in halophilic protists have undergone fewer substitutions from hydrophilic to hydrophobic residues since divergence from their closest relatives. These results suggest that these halophilic protists have a higher intracellular salt content than marine protists. However, absence of the acidic signature of salt-in microbes suggests that Haloc. seosinensis and P. kirbyi utilize organic osmolytes to maintain osmotic equilibrium. We detected increased expression of enzymes involved in synthesis and transport of organic osmolytes, namely hydroxyectoine and myo-inositol, at maximal salt concentration for growth in Haloc. seosinensis, suggesting possible candidates for these inferred organic osmolytes. PMID:27412608

18 CFR 154.315 - Asset retirement obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

18 CFR 154.315 - Asset retirement obligations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

18 CFR 154.315 - Asset retirement obligations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

18 CFR 154.315 - Asset retirement obligations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

18 CFR 154.315 - Asset retirement obligations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Asset retirement obligations. 154.315 Section 154.315 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... Filed With Changes § 154.315 Asset retirement obligations. (a) A natural gas company that files a tariff...

22 CFR 221.15 - Fiscal Agent obligations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

22 CFR 221.15 - Fiscal Agent obligations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

22 CFR 221.15 - Fiscal Agent obligations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

22 CFR 221.15 - Fiscal Agent obligations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

22 CFR 221.15 - Fiscal Agent obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fiscal Agent obligations. 221.15 Section 221.15 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEE STANDARD TERMS AND CONDITIONS The Guarantee § 221.15 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

Spatial patterns, ecological niches, and interspecific competition of avian brood parasites: inferring from a case study of Korea.

PubMed

Lee, Jin-Won; Noh, Hee-Jin; Lee, Yunkyoung; Kwon, Young-Soo; Kim, Chang-Hoe; Yoo, Jeong-Chil

2014-09-01

Since obligate avian brood parasites depend completely on the effort of other host species for rearing their progeny, the availability of hosts will be a critical resource for their life history. Circumstantial evidence suggests that intense competition for host species may exist not only within but also between species. So far, however, few studies have demonstrated whether the interspecific competition really occurs in the system of avian brood parasitism and how the nature of brood parasitism is related to their niche evolution. Using the occurrence data of five avian brood parasites from two sources of nationwide bird surveys in South Korea and publically available environmental/climatic data, we identified their distribution patterns and ecological niches, and applied species distribution modeling to infer the effect of interspecific competition on their spatial distribution. We found that the distribution patterns of five avian brood parasites could be characterized by altitude and climatic conditions, but overall their spatial ranges and ecological niches extensively overlapped with each other. We also found that the predicted distribution areas of each species were generally comparable to the realized distribution areas, and the numbers of individuals in areas where multiple species were predicted to coexist showed positive relationships among species. In conclusion, despite following different coevolutionary trajectories to adapt to their respect host species, five species of avian brood parasites breeding in South Korea occupied broadly similar ecological niches, implying that they tend to conserve ancestral preferences for ecological conditions. Furthermore, our results indicated that contrary to expectation interspecific competition for host availability between avian brood parasites seemed to be trivial, and thus, play little role in shaping their spatial distributions and ecological niches. Future studies, including the complete ranges of avian brood

26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

26 CFR 1.103-16 - Obligations of certain volunteer fire departments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Obligations of certain volunteer fire....103-16 Obligations of certain volunteer fire departments. (a) General rule. An obligation of a volunteer fire department issued after December 31, 1980, shall be treated as an obligation of a political...

18 CFR 1314.6 - Obligations of TVA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Obligations of TVA. 1314.6 Section 1314.6 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY BOOK-ENTRY PROCEDURES FOR TVA POWER SECURITIES ISSUED THROUGH THE FEDERAL RESERVE BANKS § 1314.6 Obligations of TVA. (a...

12 CFR 1.100 - Indirect general obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... powers of taxation. Pursuant to § 1.2(b), an obligation issued by an obligor not possessing general powers of taxation qualifies as a general obligation of a State or political subdivision for the purposes of 12 U.S.C. 24 (Seventh), if a party possessing general powers of taxation unconditionally promises...

New parasites and predators follow the introduction of two fish species to a subarctic lake: implications for food-web structure and functioning.

PubMed

Amundsen, Per-Arne; Lafferty, Kevin D; Knudsen, Rune; Primicerio, Raul; Kristoffersen, Roar; Klemetsen, Anders; Kuris, Armand M

2013-04-01

Introduced species can alter the topology of food webs. For instance, an introduction can aid the arrival of free-living consumers using the new species as a resource, while new parasites may also arrive with the introduced species. Food-web responses to species additions can thus be far more complex than anticipated. In a subarctic pelagic food web with free-living and parasitic species, two fish species (arctic charr Salvelinus alpinus and three-spined stickleback Gasterosteus aculeatus) have known histories as deliberate introductions. The effects of these introductions on the food web were explored by comparing the current pelagic web with a heuristic reconstruction of the pre-introduction web. Extinctions caused by these introductions could not be evaluated by this approach. The introduced fish species have become important hubs in the trophic network, interacting with numerous parasites, predators and prey. In particular, five parasite species and four predatory bird species depend on the two introduced species as obligate trophic resources in the pelagic web and could therefore not have been present in the pre-introduction network. The presence of the two introduced fish species and the arrival of their associated parasites and predators increased biodiversity, mean trophic level, linkage density, and nestedness; altering both the network structure and functioning of the pelagic web. Parasites, in particular trophically transmitted species, had a prominent role in the network alterations that followed the introductions.

New parasites and predators follow the introduction of two fish species to a subarctic lake: implications for food-web structure and functioning

USGS Publications Warehouse

Amundsen, Per-Arne; Lafferty, Kevin D.; Knudsen, Rune; Primicerio, Raul; Kristoffersen, Roar; Klemetsen, Anders; Kuris, Armand M.

2012-01-01

Introduced species can alter the topology of food webs. For instance, an introduction can aid the arrival of free-living consumers using the new species as a resource, while new parasites may also arrive with the introduced species. Food-web responses to species additions can thus be far more complex than anticipated. In a subarctic pelagic food web with free-living and parasitic species, two fish species (arctic charr Salvelinus alpinus and three-spined stickleback Gasterosteus aculeatus) have known histories as deliberate introductions. The effects of these introductions on the food web were explored by comparing the current pelagic web with a heuristic reconstruction of the pre-introduction web. Extinctions caused by these introductions could not be evaluated by this approach. The introduced fish species have become important hubs in the trophic network, interacting with numerous parasites, predators and prey. In particular, five parasite species and four predatory bird species depend on the two introduced species as obligate trophic resources in the pelagic web and could therefore not have been present in the pre-introduction network. The presence of the two introduced fish species and the arrival of their associated parasites and predators increased biodiversity, mean trophic level, linkage density, and nestedness; altering both the network structure and functioning of the pelagic web. Parasites, in particular trophically transmitted species, had a prominent role in the network alterations that followed the introductions.

Analysis of complete genome sequence of Neorickettsia risticii: causative agent of Potomac horse fever

PubMed Central

Lin, Mingqun; Zhang, Chunbin; Gibson, Kathryn; Rikihisa, Yasuko

2009-01-01

Neorickettsia risticii is an obligate intracellular bacterium of the trematodes and mammals. Horses develop Potomac horse fever (PHF) when they ingest aquatic insects containing encysted N. risticii-infected trematodes. The complete genome sequence of N. risticii Illinois consists of a single circular chromosome of 879 977 bp and encodes 38 RNA species and 898 proteins. Although N. risticii has limited ability to synthesize amino acids and lacks many metabolic pathways, it is capable of making major vitamins, cofactors and nucleotides. Comparison with its closely related human pathogen N. sennetsu showed that 758 (88.2%) of protein-coding genes are conserved between N. risticii and N. sennetsu. Four-way comparison of genes among N. risticii and other Anaplasmataceae showed that most genes are either shared among Anaplasmataceae (525 orthologs that generally associated with housekeeping functions), or specific to each genome (>200 genes that are mostly hypothetical proteins). Genes potentially involved in the pathogenesis of N. risticii were identified, including those encoding putative outer membrane proteins, two-component systems and a type IV secretion system (T4SS). The bipolar localization of T4SS pilus protein VirB2 on the bacterial surface was demonstrated for the first time in obligate intracellular bacteria. These data provide insights toward genomic potential of N. risticii and intracellular parasitism, and facilitate our understanding of PHF pathogenesis. PMID:19661282

Analysis of complete genome sequence of Neorickettsia risticii: causative agent of Potomac horse fever.

PubMed

Lin, Mingqun; Zhang, Chunbin; Gibson, Kathryn; Rikihisa, Yasuko

2009-10-01

Neorickettsia risticii is an obligate intracellular bacterium of the trematodes and mammals. Horses develop Potomac horse fever (PHF) when they ingest aquatic insects containing encysted N. risticii-infected trematodes. The complete genome sequence of N. risticii Illinois consists of a single circular chromosome of 879 977 bp and encodes 38 RNA species and 898 proteins. Although N. risticii has limited ability to synthesize amino acids and lacks many metabolic pathways, it is capable of making major vitamins, cofactors and nucleotides. Comparison with its closely related human pathogen N. sennetsu showed that 758 (88.2%) of protein-coding genes are conserved between N. risticii and N. sennetsu. Four-way comparison of genes among N. risticii and other Anaplasmataceae showed that most genes are either shared among Anaplasmataceae (525 orthologs that generally associated with housekeeping functions), or specific to each genome (>200 genes that are mostly hypothetical proteins). Genes potentially involved in the pathogenesis of N. risticii were identified, including those encoding putative outer membrane proteins, two-component systems and a type IV secretion system (T4SS). The bipolar localization of T4SS pilus protein VirB2 on the bacterial surface was demonstrated for the first time in obligate intracellular bacteria. These data provide insights toward genomic potential of N. risticii and intracellular parasitism, and facilitate our understanding of PHF pathogenesis.

CD44 mediated hyaluronan adhesion of Toxoplasma gondii-infected leukocytes.

PubMed

Hayashi, Takeshi; Unno, Akihiro; Baba, Minami; Ohno, Tamio; Kitoh, Katsuya; Takashima, Yasuhiro

2014-04-01

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects humans and animals. Ingested parasites cross the intestinal epithelium, invade leukocytes and are then disseminated to peripheral organs. However, the mechanism of extravasation of the infected leukocytes remains poorly understood. In this study, we demonstrate that T. gondii-invaded human and mouse leukocytes express higher level of CD44, a ligand of hyaluronan (HA), and its expression on myeloid and non-myeloid leukocytes causes T. gondii-invaded human and mouse leukocyte to adhere to HA more effectively than non-invaded leukocytes. The specific adherence of parasite-invaded leukocytes was inhibited by anti CD44 antibody. Leukocytes of CD44 knockout mice did not show parasite-invaded leukocyte specific adhesion. Our results indicate that parasite-invaded leukocytes, regardless of whether myeloid or not, gain higher ability to adhere to HA than non-invaded leukocytes, via upregulation of CD44 expression and/or selective invasion to CD44 highly expressing cells. The difference in ability to adhere to HA between parasite-invaded cells and non-invaded neighboring cells might facilitate effective delivery of parasite-invaded leukocytes to the HA-producing endothelial cell surface and/or HA-rich extra cellular matrix. © 2013.

Obligations of an academic and clinical oncologist: historical reflections.

PubMed

Johnson, David H

2014-01-01

Obligations are derived from one's core values-those fundamental, enduring, deeply held beliefs that guide one's everyday actions. Gandhi stated it more eloquently than I ever could: "Your beliefs become your thoughts, your thoughts become your words, your words become your actions, your actions become your habits, your habits become your values, your values become your destiny." So what are the obligations of the academic oncologist and clinician? I believe there are a few indubitable and fundamental obligations: professionalism, patient care, stewardship, maintenance of knowledge, productivity, and mentorship). I might add that I do not see these obligations as unique to the academician but rather applicable to all physicians.

The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies.

PubMed

Ben-Ami, F; Rigaud, T; Ebert, D

2011-06-01

In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less-virulent parasite may protect the host against the more-virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood-infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less-virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

CLAG3 Self-Associates in Malaria Parasites and Quantitatively Determines Nutrient Uptake Channels at the Host Membrane.

PubMed

Gupta, Ankit; Balabaskaran-Nina, Praveen; Nguitragool, Wang; Saggu, Gagandeep S; Schureck, Marc A; Desai, Sanjay A

2018-05-08

Malaria parasites increase host erythrocyte permeability to ions and nutrients via a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), linked to parasite-encoded CLAG3 and two associated proteins. These proteins lack the multiple transmembrane domains typically present in channel-forming proteins, raising doubts about their precise roles. Using the virulent human Plasmodium falciparum parasite, we report that CLAG3 undergoes self-association and that this protein's expression determines channel phenotype quantitatively. We overcame epigenetic silencing of clag3 paralogs and engineered parasites that express two CLAG3 isoforms simultaneously. Stoichiometric expression of these isoforms yielded intermediate channel phenotypes, in agreement with observed trafficking of both proteins to the host membrane. Coimmunoprecipitation and surface labeling revealed formation of CLAG3 oligomers. In vitro selections applied to these transfectant lines yielded distinct mutants with correlated changes in channel activity. These findings support involvement of the identified oligomers in PSAC formation and parasite nutrient acquisition. IMPORTANCE Malaria parasites are globally important pathogens that evade host immunity by replicating within circulating erythrocytes. To facilitate intracellular growth, these parasites increase erythrocyte nutrient uptake through an unusual ion channel. The parasite CLAG3 protein is a key determinant of this channel, but its lack of homology to known ion channels has raised questions about possible mechanisms. Using a new method that allows simultaneous expression of two different CLAG3 proteins, we identify self-association of CLAG3. The two expressed isoforms faithfully traffic to and insert in the host membrane, while remaining associated with two unrelated parasite proteins. Both the channel phenotypes and molecular changes produced upon selections with a highly specific channel inhibitor are consistent with a

Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes.

PubMed

Petri e Silva, Simone Carolina Soares; Palace-Berl, Fanny; Tavares, Leoberto Costa; Soares, Sandra Regina Castro; Lindoso, José Angelo Lauletta

2016-04-01

Leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries. Clinical manifestation depends on the interaction between Leishmania and the host's immune response. Currently available treatment options for leishmaniasis are limited and induce severe side effects. In this research, we tested nitro-heterocyclic compounds (BSF series) as a new alternative against Leishmania. Its activity was measured in Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes using MTT colorimetric assay. Additionally, we assessed the phosphatidylserine exposure by promastigotes, measured by flow cytometry, as well as nitric oxide production, measured by Griess' method. The nitro-heterocyclic compounds (BSF series) showed activity against L. (L.) infantum promastigotes, inducting the phosphatidylserine exposition by promastigotes, decreasing intracellular amastigotes and increasing oxide nitric production. The selectivity index was more prominent to Leishmania than to macrophages. Compared to amphotericin b, our compounds presented higher IC50, however the selectivity index was more specific to parasite than to amphotericin b. In conclusion, these nitro-heterocyclic compounds showed to be promising as an anti-Leishmania drug, in in vitro studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Cultivation of parasites.

PubMed

Ahmed, Nishat Hussain

2014-07-01

Parasite cultivation techniques constitute a substantial segment of present-day study of parasites, especially of protozoa. Success in establishing in vitro and in vivo culture of parasites not only allows their physiology, behavior and metabolism to be studied dynamically, but also allows the nature of the antigenic molecules in the excretory and secretory products to be vigorously pursued and analyzed. The complex life-cycles of various parasites having different stages and host species requirements, particularly in the case of parasitic helminths, often make parasite cultivation an uphill assignment. Culturing of parasites depends on the combined expertise of all types of microbiological cultures. Different parasites require different cultivation conditions such as nutrients, temperature and even incubation conditions. Cultivation is an important method for diagnosis of many clinically important parasites, for example, Entamoeba histolytica, Trichomonas vaginalis, Leishmania spp., Strongyloides stercoralis and free-living amoebae. Many commercial systems like InPouch TV for T. vaginalis, microaerophilous stationary phase culture for Babesia bovis and Harada-Mori culture technique for larval-stage nematodes have been developed for the rapid diagnosis of the parasitic infections. Cultivation also has immense utility in the production of vaccines, testing vaccine efficacy, and antigen - production for obtaining serological reagents, detection of drug-resistance, screening of potential therapeutic agents and conducting epidemiological studies. Though in vitro cultivation techniques are used more often compared with in vivo techniques, the in vivo techniques are sometimes used for diagnosing some parasitic infections such as trypanosomiasis and toxoplasmosis. Parasite cultivation continues to be a challenging diagnostic option. This review provides an overview of intricacies of parasitic culture and update on popular methods used for cultivating parasites.

Cultivation of parasites

PubMed Central

Ahmed, Nishat Hussain

2014-01-01

Parasite cultivation techniques constitute a substantial segment of present-day study of parasites, especially of protozoa. Success in establishing in vitro and in vivo culture of parasites not only allows their physiology, behavior and metabolism to be studied dynamically, but also allows the nature of the antigenic molecules in the excretory and secretory products to be vigorously pursued and analyzed. The complex life-cycles of various parasites having different stages and host species requirements, particularly in the case of parasitic helminths, often make parasite cultivation an uphill assignment. Culturing of parasites depends on the combined expertise of all types of microbiological cultures. Different parasites require different cultivation conditions such as nutrients, temperature and even incubation conditions. Cultivation is an important method for diagnosis of many clinically important parasites, for example, Entamoeba histolytica, Trichomonas vaginalis, Leishmania spp., Strongyloides stercoralis and free-living amoebae. Many commercial systems like InPouch TV for T. vaginalis, microaerophilous stationary phase culture for Babesia bovis and Harada-Mori culture technique for larval-stage nematodes have been developed for the rapid diagnosis of the parasitic infections. Cultivation also has immense utility in the production of vaccines, testing vaccine efficacy, and antigen - production for obtaining serological reagents, detection of drug-resistance, screening of potential therapeutic agents and conducting epidemiological studies. Though in vitro cultivation techniques are used more often compared with in vivo techniques, the in vivo techniques are sometimes used for diagnosing some parasitic infections such as trypanosomiasis and toxoplasmosis. Parasite cultivation continues to be a challenging diagnostic option. This review provides an overview of intricacies of parasitic culture and update on popular methods used for cultivating parasites. PMID

Genomic Diversification in Strains of Rickettsia felis Isolated from Different Arthropods

PubMed Central

Gillespie, Joseph J.; Driscoll, Timothy P.; Verhoeve, Victoria I.; Utsuki, Tadanobu; Husseneder, Claudia; Chouljenko, Vladimir N.; Azad, Abdu F.; Macaluso, Kevin R.

2015-01-01

Rickettsia felis (Alphaproteobacteria: Rickettsiales) is the causative agent of an emerging flea-borne rickettsiosis with worldwide occurrence. Originally described from the cat flea, Ctenocephalides felis, recent reports have identified R. felis from other flea species, as well as other insects and ticks. This diverse host range for R. felis may indicate an underlying genetic variability associated with host-specific strains. Accordingly, to determine a potential genetic basis for host specialization, we sequenced the genome of R. felis str. LSU-Lb, which is an obligate mutualist of the parthenogenic booklouse Liposcelis bostrychophila (Insecta: Psocoptera). We also sequenced the genome of R. felis str. LSU, the second genome sequence for cat flea-associated strains (cf. R. felis str. URRWXCal2), which are presumably facultative parasites of fleas. Phylogenomics analysis revealed R. felis str. LSU-Lb diverged from the flea-associated strains. Unexpectedly, R. felis str. LSU was found to be divergent from R. felis str. URRWXCal2, despite sharing similar hosts. Although all three R. felis genomes contain the pRF plasmid, R. felis str. LSU-Lb carries an additional unique plasmid, pLbaR (plasmid of L. bostrychophila associated Rickettsia), nearly half of which encodes a unique 23-gene integrative conjugative element. Remarkably, pLbaR also encodes a repeats-in-toxin-like type I secretion system and associated toxin, heretofore unknown from other Rickettsiales genomes, which likely originated from lateral gene transfer with another obligate intracellular parasite of arthropods, Cardinium (Bacteroidetes). Collectively, our study reveals unexpected genomic diversity across three R. felis strains and identifies several diversifying factors that differentiate facultative parasites of fleas from obligate mutualists of booklice. PMID:25477419

P-type proton ATPases are involved in intracellular calcium and proton uptake in the plant parasite Phytomonas francai.

PubMed

Miranda, Kildare; Vercesi, Anibal E; Catisti, Rosana; De Souza, Wanderley; Rodrigues, Claudia O; Docampo, Roberto

2005-01-01

The use of digitonin to permeabilize the plasma membrane of promastigotes of Phytomonas francai allowed the identification of two non-mitochondrial Ca(2+) compartments; one sensitive to ionomycin and vanadate (neutral or alkaline), possibly the endoplasmic reticulum, and another sensitive to the combination of nigericin plus ionomycin (acidic), possibly the acidocalcisomes. A P-type (phospho-intermediate form) Ca(2+)-ATPase activity was found to be responsible for intracellular Ca(2+) transport in these cells, with no evidence of a mitochondrial Ca(2+) transport activity. ATP-driven acidification of internal compartments in cell lysates and cells mechanically permeabilized was assayed spectrophotometrically with acridine orange. This activity was inhibited by low concentrations of vanadate and digitonin, was insensitive to bafilomycin A(1), and stimulated by Na(+) ions. Taken together, our results indicate that P-type ATPases are involved in intracellular Ca(2+) and H(+) transport in promastigotes of P. francai.

What are the limits to the obligations of the nurse?

PubMed Central

Edwards, S D

1996-01-01

This paper enquires into the nature and the extent of the obligations of nurses. It is argued that nurses appear to be obliged to undertake supererogatory acts if they take clause one of the United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) Code of Professional Conduct seriously (as, indeed, they are required to do). In the first part of the paper, the nature of nursing obligations is outlined, and then the groups and individuals to whom nurses have obligations are identified. Following a brief discussion of the moral foundation of the nurse's obligations to her/his employer, a common conflict of obligations is identified. Then a distinction is drawn between ordinary and extraordinary moral standards. Appreciation of this is necessary for an understanding of the criterion of what constitutes a supererogatory act. By the definition of supererogatory acts proposed below, it is suggested that actions such as whistleblowing satisfy that definition. PMID:8731534

12 CFR 208.111 - Obligations concerning institutional customers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... adopting sales practice rules for the government securities market, a market with a particularly broad... on their suitability obligations when making recommendations to institutional customers. (b) The... suitability obligations in making recommendations to an institutional customer are the customer's capability...

12 CFR 208.111 - Obligations concerning institutional customers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... adopting sales practice rules for the government securities market, a market with a particularly broad... on their suitability obligations when making recommendations to institutional customers. (b) The... suitability obligations in making recommendations to an institutional customer are the customer's capability...

12 CFR 208.111 - Obligations concerning institutional customers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... adopting sales practice rules for the government securities market, a market with a particularly broad... on their suitability obligations when making recommendations to institutional customers. (b) The... suitability obligations in making recommendations to an institutional customer are the customer's capability...

Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula.

PubMed

de Brum Vieira, Patrícia; Silva, Nícolas Luiz Feijó; Menezes, Camila Braz; da Silva, Márcia Vanusa; Silva, Denise Brentan; Lopes, Norberto Peporine; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

2017-01-01

The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a metronidazole-resistant isolate and dramatically reduced the cytoadherence of T. vaginalis to human cells. Investigation of the mechanism of death showed that the saponin fraction induced the parasite death due to profound membrane damage, inducing a disturbance of intracellular content without nuclear damage. To the best of our knowledge, this is the first report of antitrichomonal activity in the bidesmosic saponins of Manilkara rufula.

Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula

PubMed Central

Silva, Nícolas Luiz Feijó; Menezes, Camila Braz; da Silva, Márcia Vanusa; Silva, Denise Brentan; Lopes, Norberto Peporine; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

2017-01-01

The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a metronidazole-resistant isolate and dramatically reduced the cytoadherence of T. vaginalis to human cells. Investigation of the mechanism of death showed that the saponin fraction induced the parasite death due to profound membrane damage, inducing a disturbance of intracellular content without nuclear damage. To the best of our knowledge, this is the first report of antitrichomonal activity in the bidesmosic saponins of Manilkara rufula. PMID:29190689

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle.

PubMed

Armstrong, Stuart D; Xia, Dong; Bah, Germanus S; Krishna, Ritesh; Ngangyung, Henrietta F; LaCourse, E James; McSorley, Henry J; Kengne-Ouafo, Jonas A; Chounna-Ndongmo, Patrick W; Wanji, Samuel; Enyong, Peter A; Taylor, David W; Blaxter, Mark L; Wastling, Jonathan M; Tanya, Vincent N; Makepeace, Benjamin L

2016-08-01

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle*

PubMed Central

Armstrong, Stuart D.; Xia, Dong; Bah, Germanus S.; Krishna, Ritesh; Ngangyung, Henrietta F.; LaCourse, E. James; McSorley, Henry J.; Kengne-Ouafo, Jonas A.; Chounna-Ndongmo, Patrick W.; Wanji, Samuel; Enyong, Peter A.; Taylor, David W.; Blaxter, Mark L.; Wastling, Jonathan M.; Tanya, Vincent N.; Makepeace, Benjamin L.

2016-01-01

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp

Evaluation of Boldine Activity against Intracellular Amastigotes of Leishmania amazonensis.

PubMed

Salama, Isabel Cristina; Arrais-Lima, Cristina; Arrais-Silva, Wagner Welber

2017-06-01

Leishmaniasis is a neglected and endemic disease that affects poorest population mainly in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate in vitro activity of boldine against Leishmania amazonensis murine cell infection. Boldine ((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine) is an aporphine alkaloid found abundantly in the leaves/bark of boldo ( Peumus boldus Molina), a widely distributed tree native to Chile. The in vitro system consisted of murine macrophage infection with amastigotes of L. amazonensis treated with different concentrations from 50 to 600 μg/ml of boldine for 24 hr. Intracellular parasite destruction was assessed by morphological examination and boldine cytotoxicity to macrophages was tested by the MTT viability assay. When cells were treated with 100 μg/ml of boldine the reduction of parasite infection was 81% compared with untreated cultures cells. Interestingly, boldine-treatment caused a concentration-dependent decrease of macrophage infection that culminated with 96% of reduction when cells were submitted to 600 μg/ml of boldine. Cell cultures exposed to 100 μg/ml of boldine and 300 μg/ml of Glucantime ® during 24 hr showed a significant reduction of 50% in parasitized cells compared with cell cultures exposed just to Glucantime ® . The study showed that treatment with boldine produces a better effect than treatment with the reference antimonial drug, glucantime, in L. amazonensis infected macrophage. Our results suggest that boldine is a potentially useful agent for the treatment of leishmaniasis.

Evaluation of Boldine Activity against Intracellular Amastigotes of Leishmania amazonensis

PubMed Central

Salama, Isabel Cristina; Arrais-Lima, Cristina; Arrais-Silva, Wagner Welber

2017-01-01

Leishmaniasis is a neglected and endemic disease that affects poorest population mainly in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate in vitro activity of boldine against Leishmania amazonensis murine cell infection. Boldine ((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine) is an aporphine alkaloid found abundantly in the leaves/bark of boldo (Peumus boldus Molina), a widely distributed tree native to Chile. The in vitro system consisted of murine macrophage infection with amastigotes of L. amazonensis treated with different concentrations from 50 to 600 μg/ml of boldine for 24 hr. Intracellular parasite destruction was assessed by morphological examination and boldine cytotoxicity to macrophages was tested by the MTT viability assay. When cells were treated with 100 μg/ml of boldine the reduction of parasite infection was 81% compared with untreated cultures cells. Interestingly, boldine-treatment caused a concentration-dependent decrease of macrophage infection that culminated with 96% of reduction when cells were submitted to 600 μg/ml of boldine. Cell cultures exposed to 100 μg/ml of boldine and 300 μg/ml of Glucantime® during 24 hr showed a significant reduction of 50% in parasitized cells compared with cell cultures exposed just to Glucantime®. The study showed that treatment with boldine produces a better effect than treatment with the reference antimonial drug, glucantime, in L. amazonensis infected macrophage. Our results suggest that boldine is a potentially useful agent for the treatment of leishmaniasis. PMID:28719960

Evidence for suppression of immunity as a driver for genomic introgressions and host range expansion in races of Albugo candida, a generalist parasite

PubMed Central

McMullan, Mark; Gardiner, Anastasia; Bailey, Kate; Kemen, Eric; Ward, Ben J; Cevik, Volkan; Robert-Seilaniantz, Alexandre; Schultz-Larsen, Torsten; Balmuth, Alexi; Holub, Eric; van Oosterhout, Cock; Jones, Jonathan DG

2015-01-01

How generalist parasites with wide host ranges can evolve is a central question in parasite evolution. Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species. By analyzing genome sequence assemblies of five isolates, we show they represent three races that are genetically diverged by ∼1%. Despite this divergence, their genomes are mosaic-like, with ∼25% being introgressed from other races. Sequential infection experiments show that infection by adapted races enables subsequent infection of hosts by normally non-infecting races. This facilitates introgression and the exchange of effector repertoires, and may enable the evolution of novel races that can undergo clonal population expansion on new hosts. We discuss recent studies on hybridization in other eukaryotes such as yeast, Heliconius butterflies, Darwin's finches, sunflowers and cichlid fishes, and the implications of introgression for pathogen evolution in an agro-ecological environment. DOI: http://dx.doi.org/10.7554/eLife.04550.001 PMID:25723966

12 CFR 13.100 - Obligations concerning institutional customers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... market, a market with a particularly broad institutional component. Accordingly, the OCC believes it is appropriate to provide further guidance to banks on their suitability obligations when making recommendations... suitability obligations in making recommendations to an institutional customer are the customer's capability...

12 CFR 368.100 - Obligations concerning institutional customers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... securities market, a market with a particularly broad institutional component. Accordingly, the FDIC believes it is appropriate to provide further guidance to banks on their suitability obligations when making... important considerations in determining the scope of a bank's suitability obligations in making...

12 CFR 368.100 - Obligations concerning institutional customers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... securities market, a market with a particularly broad institutional component. Accordingly, the FDIC believes it is appropriate to provide further guidance to banks on their suitability obligations when making... important considerations in determining the scope of a bank's suitability obligations in making...

12 CFR 13.100 - Obligations concerning institutional customers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... market, a market with a particularly broad institutional component. Accordingly, the OCC believes it is appropriate to provide further guidance to banks on their suitability obligations when making recommendations... suitability obligations in making recommendations to an institutional customer are the customer's capability...

Conditions Promoting Mycorrhizal Parasitism Are of Minor Importance for Competitive Interactions in Two Differentially Mycotrophic Species

PubMed Central

Friede, Martina; Unger, Stephan; Hellmann, Christine; Beyschlag, Wolfram

2016-01-01

Interactions of plants with arbuscular mycorrhizal fungi (AMF) may range along a broad continuum from strong mutualism to parasitism, with mycorrhizal benefits received by the plant being determined by climatic and edaphic conditions affecting the balance between carbon costs vs. nutritional benefits. Thus, environmental conditions promoting either parasitism or mutualism can influence the mycorrhizal growth dependency (MGD) of a plant and in consequence may play an important role in plant-plant interactions. In a multifactorial field experiment we aimed at disentangling the effects of environmental and edaphic conditions, namely the availability of light, phosphorus and nitrogen, and the implications for competitive interactions between Hieracium pilosella and Corynephorus canescens for the outcome of the AMF symbiosis. Both species were planted in single, intraspecific and interspecific combinations using a target-neighbor approach with six treatments distributed along a gradient simulating conditions for the interaction between plants and AMF ranking from mutualistic to parasitic. Across all treatments we found mycorrhizal association of H. pilosella being consistently mutualistic, while pronounced parasitism was observed in C. canescens, indicating that environmental and edaphic conditions did not markedly affect the cost:benefit ratio of the mycorrhizal symbiosis in both species. Competitive interactions between both species were strongly affected by AMF, with the impact of AMF on competition being modulated by colonization. Biomass in both species was lowest when grown in interspecific competition, with colonization being increased in the less mycotrophic C. canescens, while decreased in the obligate mycotrophic H. pilosella. Although parasitism-promoting conditions negatively affected MGD in C. canescens, these effects were small as compared to growth decreases related to increased colonization levels in this species. Thus, the lack of plant control over

ATP-driven and AMPK-independent autophagy in an early branching eukaryotic parasite.

PubMed

Li, Feng-Jun; Xu, Zhi-Shen; Soo, Andy D S; Lun, Zhao-Rong; He, Cynthia Y

2017-04-03

Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabolic stimuli to initiate autophagy in higher eukaryotes. In the early-branching unicellular parasite Trypanosoma brucei, which can proliferate as procyclic form (PCF) in the tsetse fly or as bloodstream form (BSF) in animal hosts, autophagy is robustly triggered by amino acid deficiency but not by glucose depletion. Taking advantage of the clearly defined adenosine triphosphate (ATP) production pathways in T. brucei, we have shown that autophagic activity depends on the levels of cellular ATP production, using either glucose or proline as a carbon source. While autophagosome formation positively correlates with cellular ATP levels; perturbation of ATP production by removing carbon sources or genetic silencing of enzymes involved in ATP generation pathways, also inhibited autophagy. This obligate energy dependence and the lack of glucose starvation-induced autophagy in T. brucei may reflect an adaptation to its specialized, parasitic life style.

Detection Method of TOXOPLASMA GONDII Tachyzoites

NASA Astrophysics Data System (ADS)

Eassa, Souzan; Bose, Chhanda; Alusta, Pierre; Tarasenko, Olga

2011-06-01

Tachyzoites are considered to be the most important stage of Toxoplasma gondii which causes toxoplasmosis. T. gondii is, an obligate intracellular parasite which infects a wide range of cells. The present study was designed to develop a method for an early detection of T. gondii tachyzoites. The method comprised of a binding assay which was analyzed using principal component and cluster analysis. Our data showed that glycoconjugates GC1, GC2, GC3 and GC10 exhibit a significantly higher binding affinity for T. gondii tachyzoites as compared to controls (T. gondii only, PAA only, GC 1, 2, 3, and 10 only).

Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

PubMed Central

Martin, H.L.; Alsaady, I.; Howell, G.; Prandovszky, E.; Peers, C.; Robinson, P.; McConkey, G.A.

2015-01-01

Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and can result in neuropsychiatric symptoms in humans. Little is understood regarding the effects of infection on host neural processes but alterations to dopaminergic neurotransmission are implicated. We have previously reported elevated levels of dopamine (DA) in infected dopaminergic cells however the involvement of the host enzymes and fate of the produced DA were not defined. In order to clarify the effects of infection on host DA biosynthetic enzymes and DA packaging we examined enzyme levels and activity and DA accumulation and release in T. gondii-infected neurosecretory cells. Although the levels of the host tyrosine hydroxylase (TH) and DOPA decarboxylase and AADC (DDC) did not change significantly in infected cultures, DDC was found within the parasitophorous vacuole (PV), the vacuolar compartment where the parasites reside, as well as in the host cytosol in infected dopaminergic cells. Strikingly, DDC was found within the intracellular parasite cysts in infected brain tissue. This finding could provide some explanation for observations of DA within tissue cysts in infected brain as a parasite-encoded enzyme with TH activity was also localized within tissue cysts. In contrast, cellular DA packaging appeared unchanged in single-cell microamperometry experiments and only a fraction of the increased DA was accessible to high potassium-induced release. This study provides some understanding of how this parasite produces elevated DA within dopaminergic cells without the toxic ramifications of free cytosolic DA. The mechanism for synthesis and packaging of DA by T. gondii-infected dopaminergic cells may have important implications for the effects of chronic T. gondii infection on humans and animals. PMID:26297895

26 CFR 1.103-4 - Interest upon United States obligations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Interest upon United States obligations. 1.103-4... Interest upon United States obligations. (a) Issued before March 1, 1941. (1) Interest upon obligations of the United States issued on or before September 1, 1917, is exempt from tax. In the case of...

26 CFR 1.103-4 - Interest upon United States obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Interest upon United States obligations. 1.103-4... Interest upon United States obligations. (a) Issued before March 1, 1941. (1) Interest upon obligations of the United States issued on or before September 1, 1917, is exempt from tax. In the case of...

7 CFR 400.166 - Obligations of the Corporation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 6 2013-01-01 2013-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

7 CFR 400.166 - Obligations of the Corporation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 6 2012-01-01 2012-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

7 CFR 400.166 - Obligations of the Corporation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

7 CFR 400.166 - Obligations of the Corporation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 6 2014-01-01 2014-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

7 CFR 400.166 - Obligations of the Corporation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 6 2011-01-01 2011-01-01 false Obligations of the Corporation. 400.166 Section 400... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Reinsurance Agreement-Standards for... Corporation. The Agreement will include the following among the obligations of the Corporation. (a) The...

The Complete Genome of Teredinibacter turnerae T7901: An Intracellular Endosymbiont of Marine Wood-Boring Bivalves (Shipworms)

PubMed Central

Yang, Joyce C.; Madupu, Ramana; Durkin, A. Scott; Ekborg, Nathan A.; Pedamallu, Chandra S.; Hostetler, Jessica B.; Radune, Diana; Toms, Bradley S.; Henrissat, Bernard; Coutinho, Pedro M.; Schwarz, Sandra; Field, Lauren; Trindade-Silva, Amaro E.; Soares, Carlos A. G.; Elshahawi, Sherif; Hanora, Amro; Schmidt, Eric W.; Haygood, Margo G.; Posfai, Janos; Benner, Jack; Madinger, Catherine; Nove, John; Anton, Brian; Chaudhary, Kshitiz; Foster, Jeremy; Holman, Alex; Kumar, Sanjay; Lessard, Philip A.; Luyten, Yvette A.; Slatko, Barton; Wood, Nicole; Wu, Bo; Teplitski, Max; Mougous, Joseph D.; Ward, Naomi; Eisen, Jonathan A.; Badger, Jonathan H.; Distel, Daniel L.

2009-01-01

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2–40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose

Experimental shifts in egg-nest contrasts do not alter egg rejection responses in an avian host-brood parasite system.

PubMed

Hauber, Mark E; Aidala, Zachary; Igic, Branislav; Shawkey, Matthew D; Moskát, Csaba

2015-09-01

Obligate brood parasitic birds exploit their hosts to provide care for unrelated young in the nest. Potential hosts can reduce the cost of parasitism by rejecting foreign eggs from the nest. Observational, comparative, and experimental studies have concluded that most hosts use the coloration and patterning of eggshells to discriminate between own and foreign eggs in the nest. However, an alternative hypothesis is that birds use the colour contrasts between eggshells and the nest lining to identify parasitic eggs (egg-nest contrast hypothesis). In support of this hypothesis, we found that the avian perceivable chromatic contrasts between dyed eggs and unmanipulated nest linings significantly and negatively covaried with the rejection rates of different dyed eggs of the great reed warbler Acrocephalus arundinaceus, a frequently parasitized host of the common cuckoo Cuculus canorus. To experimentally test whether egg-nest contrasts influence rejection, we reciprocally dyed both eggs and the nest lining of this host species with one of two colours: orange and green. Contrary to the egg-nest contrast hypothesis, host rejection patterns in response to dyed eggs were not altered by dyeing nests, relative to unmanipulated control eggs and nests. In turn, experimental egg colour was the only significant predictor of egg rejection rate. Our results demonstrate that egg-nest contrast is a collateral, not a causal factor in egg rejection, and confirm the conclusions of previous studies that hosts can rely on the parasitic egg's appearance itself to recognize the foreign egg in the nest.

7 CFR 783.7 - Obligations of a participant.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Obligations of a participant. 783.7 Section 783.7 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS TREE ASSISTANCE PROGRAM § 783.7 Obligations of a participant. (a) Eligible...

Osmoadaptative Strategy and Its Molecular Signature in Obligately Halophilic Heterotrophic Protists.

PubMed

Harding, Tommy; Brown, Matthew W; Simpson, Alastair G B; Roger, Andrew J

2016-08-03

Halophilic microbes living in hypersaline environments must counteract the detrimental effects of low water activity and salt interference. Some halophilic prokaryotes equilibrate their intracellular osmotic strength with the extracellular milieu by importing inorganic solutes, mainly potassium. These "salt-in" organisms characteristically have proteins that are highly enriched with acidic and hydrophilic residues. In contrast, "salt-out" halophiles accumulate large amounts of organic solutes like amino acids, sugars and polyols, and lack a strong signature of halophilicity in the amino acid composition of cytoplasmic proteins. Studies to date have examined halophilic prokaryotes, yeasts, or algae, thus virtually nothing is known about the molecular adaptations of the other eukaryotic microbes, that is, heterotrophic protists (protozoa), that also thrive in hypersaline habitats. We conducted transcriptomic investigations to unravel the molecular adaptations of two obligately halophilic protists, Halocafeteria seosinensis and Pharyngomonas kirbyi Their predicted cytoplasmic proteomes showed increased hydrophilicity compared with marine protists. Furthermore, analysis of reconstructed ancestral sequences suggested that, relative to mesophiles, proteins in halophilic protists have undergone fewer substitutions from hydrophilic to hydrophobic residues since divergence from their closest relatives. These results suggest that these halophilic protists have a higher intracellular salt content than marine protists. However, absence of the acidic signature of salt-in microbes suggests that Haloc. seosinensis and P. kirbyi utilize organic osmolytes to maintain osmotic equilibrium. We detected increased expression of enzymes involved in synthesis and transport of organic osmolytes, namely hydroxyectoine and myo-inositol, at maximal salt concentration for growth in Haloc. seosinensis, suggesting possible candidates for these inferred organic osmolytes. © The Author 2016

Doubly distributing special obligations: what professional practice can learn from parenting

PubMed Central

Tilburt, Jon; Brody, Baruch

2018-01-01

A traditional ethic of medicine asserts that physicians have special obligations to individual patients with whom they have a clinical relationship. Contemporary trends in US healthcare financing like bundled payments seem to threaten traditional conceptions of special obligations of individual physicians to individual patients because their population-based focus sets a tone that seems to emphasise responsibilities for groups of patients by groups of physicians in an organisation. Prior to undertaking a cogent debate about the fate and normative weight of special obligations and a traditional ethic for contemporary healthcare, we need a deeper examination of what the traditional ethic of special obligations really means. Here we offer a conception of ‘doubly distributed’ special obligations. Physicians and similarly minded healing professionals abiding by a traditional ethic have always spread their devotion and attention across multiple patients and have shared responsibilities with physician and non-physician colleagues in much the same way devoted parents have frequently distributed their special obligations across multiple children and across multiple parents. By taking up the extended analogy of parent we argue that doubly distributing special obligations need not contradict the possibility of special obligations in restructured collective forms of healthcare delivery and financing. PMID:27125989

12 CFR 612.2270 - Purchase of System obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Purchase of System obligations. 612.2270... REFERRAL OF KNOWN OR SUSPECTED CRIMINAL VIOLATIONS Standards of Conduct § 612.2270 Purchase of System... Funding Corporation, may only purchase joint, consolidated, or Systemwide obligations that are: (1) Part...

Neospora caninum in birds: A review.

PubMed

de Barros, Luiz Daniel; Miura, Ana Carolina; Minutti, Ana Flávia; Vidotto, Odilon; Garcia, João Luis

2018-08-01

Neospora caninum is an obligate intracellular protozoan parasite that infects domestic and wild animals. Canids are considered to be definitive hosts since they may shed oocysts into the environment through their feces. The disease is recognized as one of the major causes of bovine abortion worldwide, leading to important economic losses in the dairy and beef cattle industries. Previous studies have reported N. caninum infection in different species of birds; infection in birds has been associated with increased seroprevalence and reproductive problems in dairy cattle. Although the role of birds in the epidemiological cycle of neosporosis is unknown, birds are exposed to infection because they feed on the ground and could thus contribute to parasite dissemination. This review is focused on the current state of knowledge of neosporosis in birds. Copyright © 2018 Elsevier B.V. All rights reserved.

Intestinal coccidian parasites as an underestimated cause of travellers' diarrhoea in Polish immunocompetent patients.

PubMed

Kłudkowska, Matylda; Pielok, Łukasz; Frąckowiak, Krystyna; Paul, Małgorzata

2017-09-26

Intestinal coccidian parasites are intracellular protozoa most frequently transmitted during food-borne and water-borne infections. This group of parasites is responsible for acute diarrhoeal illnesses especially among immunocompromised patients. However, they are more frequently detected in immunocompetent individuals including travellers, and they should also be considered as important etiologic factors of travellers' diarrhoea. We examined 221 immunocompetent patients hospitalized due to acute or chronic diarrhoea and other gastrointestinal symptoms after returning from international journeys to hot climates. A basic microscopical examination and acid - fast staining of stool samples was performed. Each patient was also a part of the epidemiological investigation to define potential risk factors of tropical gastrointestinal infections. Intestinal coccidiosis was confirmed in 12 out of 221 successively hospitalized patients (5.4%). The most common coccidian parasite was Cryptosporidium spp., detected in nine Polish travellers (4.1%). Cyclospora spp. was diagnosed in three cases (1.4%), including two mixed infections with Cryptosporidium spp., and Cystoisospora spp. in two other cases (0.9%). The study has revealed that intestinal coccidian parasites are a significant threat to immunocompetent travellers and should be always considered in the differential diagnosis of gastrointestinal disorders. Therefore, it is necessary to perform specialized diagnostic methods for the detection of Cryptosporidium spp., Cystoisospora spp., and Cyclospora spp. oocysts in reference parasitology laboratories. Clinical observations demonstrated simultaneously an insufficient level of knowledge in Polish tourists concerning the main risk factors of intestinal parasitic diseases during international travels, particularly to developing countries with lower economic and sanitary conditions.

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

PubMed Central

McMahon-Pratt, Diane; Saravia, Nancy Gore

2015-01-01

Background Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses. Methodology To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays. Principal Findings Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine

Bonamia parasites: a rapidly changing perspective on a genus of important mollusc pathogens.

PubMed

Engelsma, Marc Y; Culloty, Sarah C; Lynch, Sharon A; Arzul, Isabelle; Carnegie, Ryan B

2014-07-24

Organisms of the genus Bonamia are intracellular protistan parasites of oysters. To date, 4 species have been described (B. ostreae, B. exitiosa, B. perspora and B. roughleyi), although the status of B. roughleyi is controversial. Introduction especially of B. ostreae and B. exitiosa to naïve host populations has been shown to cause mass mortalities in the past and has had a dramatic impact on oyster production. Both B. ostreae and B. exitiosa are pathogens notifiable to the World Organisation for Animal Health (OIE) and the European Union. Effective management of the disease caused by these pathogens is complicated by the extensive nature of the oyster production process and limited options for disease control of the cultured stocks in open water. This review focuses on the recent advances in research on genetic relationships between Bonamia isolates, geographical distribution, susceptible host species, diagnostics, epizootiology, host-parasite interactions, and disease resistance and control of this globally important genus of oyster pathogens.

When parasites become prey: ecological and epidemiological significance of eating parasites

USGS Publications Warehouse

Johnson, Pieter T.J.; Dobson, Andrew P.; Lafferty, Kevin D.; Marcogliese, David J.; Memmott, Jane; Orlofske, Sarah A.; Poulin, Robert; Thieltges, David W.

2010-01-01

Recent efforts to include parasites in food webs have drawn attention to a previously ignored facet of foraging ecology: parasites commonly function as prey within ecosystems. Because of the high productivity of parasites, their unique nutritional composition and their pathogenicity in hosts, their consumption affects both food-web topology and disease risk in humans and wildlife. Here, we evaluate the ecological, evolutionary and epidemiological significance of feeding on parasites, including concomitant predation, grooming, predation on free-living stages and intraguild predation. Combining empirical data and theoretical models, we show that consumption of parasites is neither rare nor accidental, and that it can sharply affect parasite transmission and food web properties. Broader consideration of predation on parasites will enhance our understanding of disease control, food web structure and energy transfer, and the evolution of complex life cycles.

47 CFR 27.1184 - Triggering a reimbursement obligation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... reimbursement obligation. (a) The clearinghouse will apply the following test to determine when an AWS entity has triggered a cost-sharing obligation and therefore must pay an AWS relocator of a BRS system in... co-channel with the licensed AWS band(s) of the AWS entity; (2) An AWS relocator has paid the...

Deconfounding Distance Effects in Judgments of Moral Obligation

ERIC Educational Resources Information Center

Nagel, Jonas; Waldmann, Michael R.

2013-01-01

A heavily disputed question of moral philosophy is whether spatial distance between agent and victim is normatively relevant for the degree of obligation to help strangers in need. In this research, we focus on the associated descriptive question whether increased distance does in fact reduce individuals' sense of helping obligation. One problem…

29 CFR 4043.20 - Post-Event filing obligation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

29 CFR 4043.20 - Post-Event filing obligation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

29 CFR 4043.20 - Post-Event filing obligation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

29 CFR 4043.20 - Post-Event filing obligation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

29 CFR 4043.20 - Post-Event filing obligation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Post-Event filing obligation. 4043.20 Section 4043.20 Labor... EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.20 Post-Event filing obligation. The plan administrator and each contributing sponsor of a plan for which a...

Parasites that cause problems in Malaysia: soil-transmitted helminths and malaria parasites.

PubMed

Singh, B; Cox-Singh, J

2001-12-01

Malaysia is a developing country with a range of parasitic infections. Indeed, soil-transmitted helminths and malaria parasites continue to have a significant impact on public health in Malaysia. In this article, the prevalence and distribution of these parasites, the problems associated with parasitic infections, the control measures taken to deal with these parasites and implications for the future will be discussed.

Vitamin B6 Generated by Obligate Symbionts Is Critical for Maintaining Proline Homeostasis and Fecundity in Tsetse Flies

PubMed Central

Michalkova, Veronika; Weiss, Brian L.; Attardo, Geoffrey M.; Aksoy, Serap

2014-01-01

The viviparous tsetse fly utilizes proline as a hemolymph-borne energy source. In tsetse, biosynthesis of proline from alanine involves the enzyme alanine-glyoxylate aminotransferase (AGAT), which requires pyridoxal phosphate (vitamin B6) as a cofactor. This vitamin can be synthesized by tsetse's obligate symbiont, Wigglesworthia glossinidia. In this study, we examined the role of Wigglesworthia-produced vitamin B6 for maintenance of proline homeostasis, specifically during the energetically expensive lactation period of the tsetse's reproductive cycle. We found that expression of agat, as well as genes involved in vitamin B6 metabolism in both host and symbiont, increases in lactating flies. Removal of symbionts via antibiotic treatment of flies (aposymbiotic) led to hypoprolinemia, reduced levels of vitamin B6 in lactating females, and decreased fecundity. Proline homeostasis and fecundity recovered partially when aposymbiotic tsetse were fed a diet supplemented with either yeast or Wigglesworthia extracts. RNA interference-mediated knockdown of agat in wild-type flies reduced hemolymph proline levels to that of aposymbiotic females. Aposymbiotic flies treated with agat short interfering RNA (siRNA) remained hypoprolinemic even upon dietary supplementation with microbial extracts or B vitamins. Flies infected with parasitic African trypanosomes display lower hemolymph proline levels, suggesting that the reduced fecundity observed in parasitized flies could result from parasite interference with proline homeostasis. This interference could be manifested by competition between tsetse and trypanosomes for vitamins, proline, or other factors involved in their synthesis. Collectively, these results indicate that the presence of Wigglesworthia in tsetse is critical for the maintenance of proline homeostasis through vitamin B6 production. PMID:25038091

Parasitization by Scleroderma guani influences expression of superoxide dismutase genes in Tenebrio molitor.

PubMed

Zhu, Jia-Ying; Ze, Sang-Zi; Stanley, David W; Yang, Bin

2014-09-01

Superoxide dismutase (SOD) is an antioxidant enzyme involved in detoxifying reactive oxygen species. In this study, we identified genes encoding the extracellular and intracellular copper-zinc SODs (ecCuZnSOD and icCuZnSOD) and a manganese SOD (MnSOD) in the yellow mealworm beetle, Tenebrio molitor. The cDNAs for ecCuZnSOD, icCuZnSOD, and MnSOD, respectively, encode 24.55, 15.81, and 23.14 kDa polypeptides, which possess structural features typical of other insect SODs. They showed 20-94% identity to other known SOD sequences from Bombyx mori, Musca domestica, Nasonia vitripennis, Pediculus humanus corporis, and Tribolium castaneum. Expression of these genes was analyzed in selected tissues and developmental stages, and following exposure to Escherichia coli and parasitization by Scleroderma guani. We recorded expression of all three SODs in cuticle, fat body, and hemocytes and in the major developmental stages. Relatively higher expressions were detected in late-instar larvae and pupae, compared to other developmental stages. Transcriptional levels were upregulated following bacterial infection. Analysis of pupae parasitized by S. guani revealed that expression of T. molitor SOD genes was significantly induced following parasitization. We infer that these genes act in immune response and in host-parasitoid interactions. © 2014 Wiley Periodicals, Inc.

Developmental Stage of Parasites Influences the Structure of Fish-Parasite Networks

PubMed Central

Bellay, Sybelle; de Oliveira, Edson Fontes; Almeida-Neto, Mário; Lima Junior, Dilermando Pereira; Takemoto, Ricardo Massato; Luque, José Luis

2013-01-01

Specialized interactions tend to be more common in systems that require strong reciprocal adaptation between species, such as those observed between parasites and hosts. Parasites exhibit a high diversity of species and life history strategies, presenting host specificity which increases the complexity of these antagonistic systems. However, most studies are limited to the description of interactions between a few parasite and host species, which restricts our understanding of these systems as a whole. We investigated the effect of the developmental stage of the parasite on the structure of 30 metazoan fish-parasite networks, with an emphasis on the specificity of the interactions, connectance and modularity. We assessed the functional role of each species in modular networks and its interactions within and among the modules according to the developmental stage (larval and adult) and taxonomic group of the parasites. We observed that most parasite and host species perform a few interactions but that parasites at the larval stage tended to be generalists, increasing the network connectivity within and among modules. The parasite groups did not differ among each other in the number of interactions within and among the modules when considering only species at the larval stage. However, the same groups of adult individuals differed from each other in their interaction patterns, which were related to variations in the degree of host specificity at this stage. Our results show that the interaction pattern of fishes with parasites, such as acanthocephalans, cestodes, digeneans and nematodes, is more closely associated with their developmental stage than their phylogenetic history. This finding corroborates the hypothesis that the life history of parasites results in adaptations that cross phylogenetic boundaries. PMID:24124506

Developmental stage of parasites influences the structure of fish-parasite networks.

PubMed

Bellay, Sybelle; de Oliveira, Edson Fontes; Almeida-Neto, Mário; Lima Junior, Dilermando Pereira; Takemoto, Ricardo Massato; Luque, José Luis

2013-01-01

Specialized interactions tend to be more common in systems that require strong reciprocal adaptation between species, such as those observed between parasites and hosts. Parasites exhibit a high diversity of species and life history strategies, presenting host specificity which increases the complexity of these antagonistic systems. However, most studies are limited to the description of interactions between a few parasite and host species, which restricts our understanding of these systems as a whole. We investigated the effect of the developmental stage of the parasite on the structure of 30 metazoan fish-parasite networks, with an emphasis on the specificity of the interactions, connectance and modularity. We assessed the functional role of each species in modular networks and its interactions within and among the modules according to the developmental stage (larval and adult) and taxonomic group of the parasites. We observed that most parasite and host species perform a few interactions but that parasites at the larval stage tended to be generalists, increasing the network connectivity within and among modules. The parasite groups did not differ among each other in the number of interactions within and among the modules when considering only species at the larval stage. However, the same groups of adult individuals differed from each other in their interaction patterns, which were related to variations in the degree of host specificity at this stage. Our results show that the interaction pattern of fishes with parasites, such as acanthocephalans, cestodes, digeneans and nematodes, is more closely associated with their developmental stage than their phylogenetic history. This finding corroborates the hypothesis that the life history of parasites results in adaptations that cross phylogenetic boundaries.

Parasites and cancers: parasite antigens as possible targets for cancer immunotherapy.

PubMed

Darani, Hossein Yousofi; Yousefi, Morteza

2012-12-01

An adverse relationship between some parasite infections and cancer in the human population has been reported by different research groups. Anticancer activity of some parasites such as Trypanosoma cruzi, Toxoplasma gondii, Toxocara canis, Acantamoeba castellani and Plasmodium yoelii has been shown in experimental animals. Moreover, it has been shown that cancer-associated mucin-type O-glycan compositions are made by parasites, therefore cancers and parasites have common antigens. In this report anticancer activities of some parasites have been reviewed and the possible mechanisms of these actions have also been discussed.

An Extended Role-Based Access Control Model for Delegating Obligations

NASA Astrophysics Data System (ADS)

Ben-Ghorbel-Talbi, Meriam; Cuppens, Frédéric; Cuppens-Boulahia, Nora; Bouhoula, Adel

The main aim of access control models is to provide means to simplify the management of the security policy, which is a fastidious and error-prone task. Supporting delegation is considered as an important mean to decentralize the administration and therefore to allow security policy to be more flexible and easier to manipulate. Our main contribution is the proposition of a unified model to the administration and delegation of obligations. Managing such delegations implies more requirements than managing traditional privileges delegation. In fact, delegating obligations may include two interpretations: the delegation of the obligation and the delegation of the responsibility related to this obligation. Therefore, it is important to deal with these two notions separately. Moreover, since delegating an obligation involves the delegation of sanctions, then the consent of the user who receives this delegation may be required in some cases. We address in this paper these requirements and we propose a formalism to deal with them.

Altered expression of an RBP-associated arginine methyltransferase 7 in Leishmania major affects parasite infection.

PubMed

Ferreira, Tiago R; Alves-Ferreira, Eliza V C; Defina, Tania P A; Walrad, Pegine; Papadopoulou, Barbara; Cruz, Angela K

2014-10-08

Protein arginine methylation is a widely conserved post-translational modification performed by arginine methyltransferases (PRMTs). However, its functional role in parasitic protozoa is still under-explored. The Leishmania major genome encodes five PRMT homologs, including PRMT7. Here we show that LmjPRMT7 expression and arginine monomethylation are tightly regulated in a lifecycle stage-dependent manner. LmjPRMT7 levels are higher during the early promastigote logarithmic phase, negligible at stationary and late-stationary phases and rise once more post-differentiation to intracellular amastigotes. Immunofluorescence and co-immunoprecipitation studies demonstrate that LmjPRMT7 is a cytosolic protein associated with several RNA-binding proteins (RBPs) from which Alba20 is monomethylated only in LmjPRMT7-expressing promastigote stages. In addition, Alba20 protein levels are significantly altered in stationary promastigotes of the LmjPRMT7 knockout mutant. Considering RBPs are well-known mammalian PRMT substrates, our data suggest that arginine methylation via LmjPRMT7 may modulate RBP function during Leishmania spp. lifecycle progression. Importantly, genomic deletion of the LmjPRMT7 gene leads to an increase in parasite infectivity both in vitro and in vivo, while lesion progression is significantly reduced in LmjPRMT7-overexpressing parasites. This study is the first to describe a role of Leishmania protein arginine methylation in host-parasite interactions. © 2014 John Wiley & Sons Ltd.

19 CFR 4.94 - Yacht privileges and obligations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Yacht privileges and obligations. 4.94 Section 4... THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES General § 4.94 Yacht privileges and obligations...) A cruising license may be issued to a yacht of a foreign country only if it has been made to appear...

19 CFR 4.94 - Yacht privileges and obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Yacht privileges and obligations. 4.94 Section 4... THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES General § 4.94 Yacht privileges and obligations...) A cruising license may be issued to a yacht of a foreign country only if it has been made to appear...

In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii

PubMed Central

De León-Nava, Marco A.; Romero-Núñez, Eunice; Luna-Nophal, Angélica; Bernáldez-Sarabia, Johanna; Sánchez-Campos, Liliana N.; Licea-Navarro, Alexei F.; Morales-Montor, Jorge; Muñiz-Hernández, Saé

2016-01-01

Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world’s population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T. gondii. We examined the effects of the synthetic toxin cal14.1a (s-cal14.1a) from C. californicus on the tachyzoite form of T. gondii. Our results indicate that, at micromolar concentrations, s-cal14.1a lowers viability and inhibits host cell invasion (by 50% and 61%, respectively) on exposure to extracellular parasites. Further, intracellular replication decreased significantly while viability of the host cell was unaffected. Our study is the first report on the antiparasitic activity of a synthetic toxin of C. californicus. PMID:27070627

In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii.

PubMed

De León-Nava, Marco A; Romero-Núñez, Eunice; Luna-Nophal, Angélica; Bernáldez-Sarabia, Johanna; Sánchez-Campos, Liliana N; Licea-Navarro, Alexei F; Morales-Montor, Jorge; Muñiz-Hernández, Saé

2016-04-08

Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world's population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T. gondii. We examined the effects of the synthetic toxin cal14.1a (s-cal14.1a) from C. californicus on the tachyzoite form of T. gondii. Our results indicate that, at micromolar concentrations, s-cal14.1a lowers viability and inhibits host cell invasion (by 50% and 61%, respectively) on exposure to extracellular parasites. Further, intracellular replication decreased significantly while viability of the host cell was unaffected. Our study is the first report on the antiparasitic activity of a synthetic toxin of C. californicus.

Presence of ecto-protein tyrosine phosphatase activity is vital for survival of Setaria cervi, a bovine filarial parasite.

PubMed

Singh, Neetu; Heneberg, Petr; Rathaur, Sushma

2014-10-01

The ecto protein tyrosine phosphatases (PTP) are known to play a crucial role in the pathogenesis and survival of the intracellular parasites. However, their presence and role in filarial parasites is still unknown. We found a significant amount of tyrosine phosphatase activity in the surface antigen fraction extracted from Setaria cervi (S. cervi), a bovine filarial parasite. An antibody designed against the conserved catalytic core of human protein tyrosine phosphatases, PTP1B cross reacted with a 63 kDa band in the surface antigen. We detected a significant amount of PTP activity in the intact S. cervi adult parasites as well as microfilariae in this study for the first time. This PTP may be localized on the surface of the parasite with an exposed active site available for the external substrates. The PTP activity was also inhibited by sodium orthovanadate and phenyl arsine oxide, specific inhibitors of PTP in both the life stages. The Km and Vmax for PTP in the adult parasites and microfilariae were determined to be 2.574 ± 0.14 mM; 206.3 ± 2.75 μM Pi/h/two parasites and 5.510 ± 0.59 mM; 62.27 ± 2.27 μM Pi/h/10(6) parasites respectively using O-P-L-Tyrosine as substrate. Interestingly, a positive correlation was observed between the inhibition in PTP activity and reduction in the motility/ viability of the parasites when they were subjected to the specific PTP inhibitors (Orthovanadate and Phenyl arsine oxide) for 4 h in the KRB maintenance medium. The activity was also significantly inhibited in the parasites exposed to antifilarial drug/compounds for e.g. Diethylcarbamazine, Acetylsalicylic Acid and SK7, a methyl chalcone. Therefore suggesting a possible role played by PTP in the survival of the parasite, its interaction with the host as well as in the screening of newly synthesized antifilarials/drugs.

Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure-response relationships.

PubMed

Kip, Anke E; Castro, María Del Mar; Gomez, Maria Adelaida; Cossio, Alexandra; Schellens, Jan H M; Beijnen, Jos H; Saravia, Nancy Gore; Dorlo, Thomas P C

2018-05-10

Leishmania parasites reside within macrophages and the direct target of antileishmanial drugs is therefore intracellular. We aimed to characterize the intracellular PBMC miltefosine kinetics by developing a population pharmacokinetic (PK) model simultaneously describing plasma and intracellular PBMC pharmacokinetics. Furthermore, we explored exposure-response relationships and simulated alternative dosing regimens. A population PK model was developed with NONMEM, based on 339 plasma and 194 PBMC miltefosine concentrations from Colombian cutaneous leishmaniasis patients [29 children (2-12 years old) and 22 adults] receiving 1.8-2.5 mg/kg/day miltefosine for 28 days. A three-compartment model with miltefosine distribution into an intracellular PBMC effect compartment best fitted the data. Intracellular PBMC distribution was described with an intracellular-to-plasma concentration ratio of 2.17 [relative standard error (RSE) 4.9%] and intracellular distribution rate constant of 1.23 day-1 (RSE 14%). In exploring exposure-response relationships, both plasma and intracellular model-based exposure estimates significantly influenced probability of cure. A proposed PK target for the area under the plasma concentration-time curve (day 0-28) of >535 mg·day/L corresponded to >95% probability of cure. In linear dosing simulations, 18.3% of children compared with 2.8% of adults failed to reach 535 mg·day/L. In children, this decreased to 1.8% after allometric dosing simulation. The developed population PK model described the rate and extent of miltefosine distribution from plasma into PBMCs. Miltefosine exposure was significantly related to probability of cure in this cutaneous leishmaniasis patient population. We propose an exploratory PK target, which should be validated in a larger cohort study.

Obligations of low income countries in ensuring equity in global health financing.

PubMed

Barugahare, John; Lie, Reidar K

2015-09-08

Despite common recognition of joint responsibility for global health by all countries particularly to ensure justice in global health, current discussions of countries' obligations for global health largely ignore obligations of developing countries. This is especially the case with regards to obligations relating to health financing. Bearing in mind that it is not possible to achieve justice in global health without achieving equity in health financing at both domestic and global levels, our aim is to show how fulfilling the obligation we propose will make it easy to achieve equity in health financing at both domestic and international levels. Achieving equity in global health financing is a crucial step towards achieving justice in global health. Our general view is that current discussions on global health equity largely ignore obligations of Low Income Country (LIC) governments and we recommend that these obligations should be mainstreamed in current discussions. While we recognise that various obligations need to be fulfilled in order to ultimately achieve justice in global health, for lack of space we prioritise obligations for health financing. Basing on the evidence that in most LICs health is not given priority in annual budget allocations, we propose that LIC governments should bear an obligation to allocate a certain minimum percent of their annual domestic budget resources to health, while they await external resources to supplement domestic ones. We recommend and demonstrate a mechanism for coordinating this obligation so that if the resulting obligations are fulfilled by both LIC and HIC governments it will be easy to achieve equity in global health financing. Although achieving justice in global health will depend on fulfillment of different categories of obligations, ensuring inter- and intra-country equity in health financing is pivotal. This can be achieved by requiring all LIC governments to allocate a certain optimal per cent of their domestic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kyrpides, Nikos; Anderson, Iain; Rodriguez, Jason

We report the complete genome of Thermofilum pendens, a deep-branching, hyperthermophilic member of the order Thermoproteales within the archaeal kingdom Crenarchaeota. T. pendens is a sulfur-dependent, anaerobic heterotroph isolated from a solfatara in Iceland. It is an extracellular commensal, requiring an extract of Thermoproteus tenax for growth, and the genome sequence reveals that biosynthetic pathways for purines, most amino acids, and most cofactors are absent. In fact T. pendens has fewer biosynthetic enzymes than obligate intracellular parasites, although it does not display other features common among obligate parasites and thus does not appear to be in the process of becomingmore » a parasite. It appears that T. pendens has adapted to life in an environment rich in nutrients. T. pendens was known to utilize peptides as an energy source, but the genome reveals substantial ability to grow on carbohydrates. T. pendens is the first crenarchaeote and only the second archaeon found to have a transporter of the phosphotransferase system. In addition to fermentation, T. pendens may gain energy from sulfur reduction with hydrogen and formate as electron donors. It may also be capable of sulfur-independent growth on formate with formate hydrogenlyase. Additional novel features are the presence of a monomethylamine:corrinoid methyltransferase, the first time this enzyme has been found outside of Methanosarcinales, and a presenilin-related protein. Predicted highly expressed proteins do not include housekeeping genes, and instead include ABC transporters for carbohydrates and peptides, and CRISPR-associated proteins.« less

18 CFR 292.311 - Reinstatement of obligation to purchase.

Code of Federal Regulations, 2010 CFR

2010-04-01

... electric energy, a qualifying cogeneration facility, a qualifying small power production facility, a State... utility's obligation to purchase electric energy under this section. Such application shall set forth the... application reinstating the electric utility's obligation to purchase electric energy under this section if...

18 CFR 292.311 - Reinstatement of obligation to purchase.

Code of Federal Regulations, 2011 CFR

2011-04-01

... electric energy, a qualifying cogeneration facility, a qualifying small power production facility, a State... utility's obligation to purchase electric energy under this section. Such application shall set forth the... application reinstating the electric utility's obligation to purchase electric energy under this section if...

A PKA survival pathway inhibited by DPT-PKI, a new specific cell permeable PKA inhibitor, is induced by T. annulata in parasitized B-lymphocytes.

PubMed

Guergnon, Julien; Dessauge, Frederic; Traincard, François; Cayla, Xavier; Rebollo, Angelita; Bost, Pierre Etienne; Langsley, Gordon; Garcia, Alphonse

2006-08-01

T. annulata, an intracellular pathogenic parasite of the Aplicomplexa protozoan family infects bovine B-lymphocytes and macrophages. Parasitized cells that become transformed survive and proliferate independently of exogenous growth factors. In the present study, we used the isogenic non parasitized BL3 and parasitized TBL3 B cell lines, as a model to evaluate the contribution of two-major PI3-K- and PKA-dependent anti-apoptotic pathways in the survival of T. annulata parasitized B lymphocytes. We found that T. annulata increases PKA activity, induces over-expression of the catalytic subunit and down-regulates the pro-survival phosphorylation state of Akt/PKB. Consistent with a role of PKA activation in survival, two pharmacological inhibitors H89 and KT5720 ablate PKA-dependent survival of parasitized cells. To specifically inhibit PKA pro-survival pathways we linked the DPTsh1 peptide shuttle sequence to PKI(5-24) and we generated DPT-PKI, a cell permeable PKI. DPT-PKI specifically inhibited PKA activity in bovine cell extracts and, as expected, also inhibited the PKA-dependent survival of T. annulata parasitized TBL3 cells. Thus, parasite-dependent constitutive activation of PKA in TBL3 cells generates an anti-apoptotic pathway that can protect T. annulata-infected B cells from apoptosis. These results also indicate that DPT-PKI could be a powerful tool to inhibit PKA pathways in other cell types.

Leishmania HASP and SHERP Genes Are Required for In Vivo Differentiation, Parasite Transmission and Virulence Attenuation in the Host

PubMed Central

Doehl, Johannes S. P.; Sádlová, Jovana; Aslan, Hamide; Pružinová, Kateřina; Votýpka, Jan; Kamhawi, Shaden; Volf, Petr

2017-01-01

Differentiation of extracellular Leishmania promastigotes within their sand fly vector, termed metacyclogenesis, is considered to be essential for parasites to regain mammalian host infectivity. Metacyclogenesis is accompanied by changes in the local parasite environment, including secretion of complex glycoconjugates within the promastigote secretory gel and colonization and degradation of the sand fly stomodeal valve. Deletion of the stage-regulated HASP and SHERP genes on chromosome 23 of Leishmania major is known to stall metacyclogenesis in the sand fly but not in in vitro culture. Here, parasite mutants deficient in specific genes within the HASP/SHERP chromosomal region have been used to investigate their role in metacyclogenesis, parasite transmission and establishment of infection. Metacyclogenesis was stalled in HASP/SHERP mutants in vivo and, although still capable of osmotaxis, these mutants failed to secrete promastigote secretory gel, correlating with a lack of parasite accumulation in the thoracic midgut and failure to colonise the stomodeal valve. These defects prevented parasite transmission to a new mammalian host. Sand fly midgut homogenates modulated parasite behaviour in vitro, suggesting a role for molecular interactions between parasite and vector in Leishmania development within the sand fly. For the first time, stage-regulated expression of the small HASPA proteins in Leishmania (Leishmania) has been demonstrated: HASPA2 is expressed only in extracellular promastigotes and HASPA1 only in intracellular amastigotes. Despite its lack of expression in amastigotes, replacement of HASPA2 into the null locus background delays onset of pathology in BALB/c mice. This HASPA2-dependent effect is reversed by HASPA1 gene addition, suggesting that the HASPAs may have a role in host immunomodulation. PMID:28095465

Avirulence Effector Discovery in a Plant Galling and Plant Parasitic Arthropod, the Hessian Fly (Mayetiola destructor)

PubMed Central

Aggarwal, Rajat; Subramanyam, Subhashree; Zhao, Chaoyang; Chen, Ming-Shun; Harris, Marion O.; Stuart, Jeff J.

2014-01-01

Highly specialized obligate plant-parasites exist within several groups of arthropods (insects and mites). Many of these are important pests, but the molecular basis of their parasitism and its evolution are poorly understood. One hypothesis is that plant parasitic arthropods use effector proteins to defeat basal plant immunity and modulate plant growth. Because avirulence (Avr) gene discovery is a reliable method of effector identification, we tested this hypothesis using high-resolution molecular genetic mapping of an Avr gene (vH13) in the Hessian fly (HF, Mayetiola destructor), an important gall midge pest of wheat (Triticum spp.). Chromosome walking resolved the position of vH13, and revealed alleles that determine whether HF larvae are virulent (survive) or avirulent (die) on wheat seedlings carrying the wheat H13 resistance gene. Association mapping found three independent insertions in vH13 that appear to be responsible for H13-virulence in field populations. We observed vH13 transcription in H13-avirulent larvae and the salivary glands of H13-avirulent larvae, but not in H13-virulent larvae. RNA-interference-knockdown of vH13 transcripts allowed some H13-avirulent larvae to escape H13-directed resistance. vH13 is the first Avr gene identified in an arthropod. It encodes a small modular protein with no sequence similarities to other proteins in GenBank. These data clearly support the hypothesis that an effector-based strategy has evolved in multiple lineages of plant parasites, including arthropods. PMID:24964065

Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata.

PubMed

Zahoor, Zahida; Davies, Angela J; Kirk, Ruth S; Rollinson, David; Walker, Anthony John

2010-09-01

Synthesis of heat shock proteins (HSPs) following cellular stress is a response shared by many organisms. Amongst the HSP family, the approximately 70 kDa HSPs are the most evolutionarily conserved with intracellular chaperone and extracellular immunoregulatory functions. This study focused on the effects of larval excretory-secretory products (ESPs) from the parasite Schistosoma mansoni on HSP70 protein expression levels in haemocytes (defence cells) from its snail intermediate host Biomphalaria glabrata. S. mansoni larval stage ESPs are known to interfere with haemocyte physiology and behaviour. Haemocytes from two different B. glabrata strains, one which is susceptible to S. mansoni infection and one which is resistant, both showed reduced HSP70 protein levels following 1 h challenge with S. mansoni ESPs when compared to unchallenged controls; however, the reduction observed in the resistant strain was less marked. The decline in intracellular HSP70 protein persisted for at least 5 h in resistant snail haemocytes only. Furthermore, in schistosome-susceptible snails infected by S. mansoni for 35 days, haemocytes possessed approximately 70% less HSP70. The proteasome inhibitor, MG132, partially restored HSP70 protein levels in ESP-challenged haemocytes, demonstrating that the decrease in HSP70 was in part due to intracellular degradation. The extracellular signal-regulated kinase (ERK) signalling pathway appears to regulate HSP70 protein expression in these cells, as the mitogen-activated protein-ERK kinase 1/2 (MEK1/2) inhibitor, U0126, significantly reduced HSP70 protein levels. Disruption of intracellular HSP70 protein expression in B. glabrata haemocytes by S. mansoni ESPs may be a strategy employed by the parasite to manipulate the immune response of the intermediate snail host.

47 CFR 64.3001 - Obligation to transmit 911 calls.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

47 CFR 64.3001 - Obligation to transmit 911 calls.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

47 CFR 64.3001 - Obligation to transmit 911 calls.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

47 CFR 64.3001 - Obligation to transmit 911 calls.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

47 CFR 64.3001 - Obligation to transmit 911 calls.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Obligation to transmit 911 calls. 64.3001 Section 64.3001 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Obligation to transmit 911 calls. All telecommunications carriers shall transmit all 911 calls to a PSAP, to...

Fishing drives declines in fish parasite diversity and has variable effects on parasite abundance.

PubMed

Wood, Chelsea L; Sandin, Stuart A; Zgliczynski, Brian; Guerra, Ana Sofía; Micheli, Fiorenza

2014-07-01

Despite the ubiquity and ecological importance of parasites, relatively few studies have assessed their response to anthropogenic environmental change. Heuristic models have predicted both increases and decreases in parasite abundance in response to human disturbance, with empirical support for both. However, most studies focus on one or a few selected parasite species. Here, we assess the abundance of parasites of seven species of coral reef fishes collected from three fished and three unfished islands of the Line Islands archipelago in the central equatorial Pacific. Because we chose fish hosts that spanned different trophic levels, taxonomic groups, and body sizes, we were able to compare parasite responses across a broad cross section of the total parasite community in the presence and absence of fishing, a major human impact on marine ecosystems. We found that overall parasite species richness was substantially depressed on fished islands, but that the response of parasite abundance varied among parasite taxa: directly transmitted parasites were significantly more abundant on fished than on unfished islands, while the reverse was true for trophically transmitted parasites. This probably arises because trophically transmitted parasites require multiple host species, some of which are the top predators most sensitive to fishing impacts. The increase in directly transmitted parasites appeared to be due to fishing-driven compensatory increases in the abundance of their hosts. Together, these results provide support for the predictions of both heuristic models, and indicate that the direction of fishing's impact on parasite abundance is mediated by parasite traits, notably parasite transmission strategies.

Nature, nomenclature and taxonomy of obligate methanol utilizing strains.

PubMed

Cercel, M

1999-01-01

In a screening program, a number of different bacterial strains with the ability to utilize methanol as a sole carbon and energy source were isolated and described. They are well known methanol utilizing genera Pseudomonas, Klebsiella, Micrococcus, Methylomonas or, on the contrary, the new, unknown genera and species of methylotrophic bacteria. In the last category, Acinetobacter and Alcaligenes are the new reported genera of organisms able to use methanol as a sole carbon and energy source. The present paper reports the very complex physiological and biochemical modifications when very versatile bacteria such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus are cultured on methanol and when the obligate methylotrophic state is compared with the facultative methylotrophic state of the same bacterial strain. Based on experiments and comparisons with literature data, it seems that Methylomonas methanica is the obligate methylotrophic state of Pseudomonas aeruginosa and that Acinetobacter calcoaceticus is the facultative methylotrophic state of Methylococcus capsulatus, an obligate methylotroph. The relationship of the obligate to the facultative and of the facultative to the obligate methylotrophy were established. These new methylotrophic genera and species, the profound physiological and biochemical modifications as well as the new data concerning nature, nomenclature and taxonomy of methanol utilizing bateria were reported for the first time in 1983.

Paradigms for parasite conservation.

PubMed

Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

2016-08-01

Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

In Vitro Alterations Do Not Reflect a Requirement for Host Cell Cycle Progression during Plasmodium Liver Stage Infection

PubMed Central

Hanson, Kirsten K.; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N.

2014-01-01

Prior to invading nonreplicative erythrocytes, Plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. While normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. Many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but it is not known whether the hepatocyte cell cycle plays a role during Plasmodium liver stage infection. Here, we show that Plasmodium parasites can be observed in mitotic hepatoma cells throughout liver stage development, where they initially reduce the likelihood of mitosis and ultimately lead to significant acquisition of a binucleate phenotype. However, hepatoma cells pharmacologically arrested in S phase still support robust and complete Plasmodium liver stage development, which thus does not require cell cycle progression in the infected cell in vitro. Furthermore, murine hepatocytes remain quiescent throughout in vivo infection with either Plasmodium berghei or Plasmodium yoelii, as do Plasmodium falciparum-infected primary human hepatocytes, demonstrating that the rapid and prodigious growth of liver stage parasites is accomplished independent of host hepatocyte cell cycle progression during natural infection. PMID:25416236

Dehydrocostus lactone is exuded from sunflower roots and stimulates germination of the root parasite Orobanche cumana.

PubMed

Joel, Daniel M; Chaudhuri, Swapan K; Plakhine, Dina; Ziadna, Hammam; Steffens, John C

2011-05-01

The germination of the obligate root parasites of the Orobanchaceae depends on the perception of chemical stimuli from host roots. Several compounds, collectively termed strigolactones, stimulate the germination of the various Orobanche species, but do not significantly elicit germination of Orobanche cumana, a specific parasite of sunflower. Phosphate starvation markedly decreased the stimulatory activity of sunflower root exudates toward O. cumana, and fluridone - an inhibitor of the carotenoid biosynthesis pathway - did not inhibit the production of the germination stimulant in both shoots and roots of young sunflower plants, indicating that the stimulant is not a strigolactone. We identified the natural germination stimulant from sunflower root exudates by bioassay-driven purification. Its chemical structure was elucidated as the guaianolide sesquiterpene lactone dehydrocostus lactone (DCL). Low DCL concentrations effectively stimulate the germination of O. cumana seeds but not of Phelipanche aegyptiaca (syn. Orobanche aegyptiaca). DCL and other sesquiterpene lactones were found in various plant organs, but were previously not known to be exuded to the rhizosphere where they can interact with other organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.