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Sample records for secondary host resistances

  1. An overview of NMR-based metabolomics to identify secondary plant compounds involved in host plant resistance.

    PubMed

    Leiss, Kirsten A; Choi, Young H; Verpoorte, Robert; Klinkhamer, Peter G L

    2011-06-01

    Secondary metabolites provide a potential source for the generation of host plant resistance and development of biopesticides. This is especially important in view of the rapid and vast spread of agricultural and horticultural pests worldwide. Multiple pests control tactics in the framework of an integrated pest management (IPM) programme are necessary. One important strategy of IPM is the use of chemical host plant resistance. Up to now the study of chemical host plant resistance has, for technical reasons, been restricted to the identification of single compounds applying specific chemical analyses adapted to the compound in question. In biological processes however, usually more than one compound is involved. Metabolomics allows the simultaneous detection of a wide range of compounds, providing an immediate image of the metabolome of a plant. One of the most universally used metabolomic approaches comprises nuclear magnetic resonance spectroscopy (NMR). It has been NMR which has been applied as a proof of principle to show that metabolomics can constitute a major advancement in the study of host plant resistance. Here we give an overview on the application of NMR to identify candidate compounds for host plant resistance. We focus on host plant resistance to western flower thrips (Frankliniella occidentalis) which has been used as a model for different plant species. PMID:21765818

  2. Host Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concepts covered in this chapter (for an undergraduate text book) • Disease resistance is a crucial trait for any crop plant. • The degree of disease resistance varies within plant populations. Much of this variation has a genetic basis. • Plant disease resistance can be broadly categorized into s...

  3. Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice

    SciTech Connect

    Guo, Tai L. . E-mail: tlguo@hsc.vcu.edu; Chi, Rui P.; Karrow, Niel A.; Zhang, Ling X.; Pruett, Stephen B.; Germolec, Dori R.; White, Kimber L.

    2005-12-15

    Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8{sup +} T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice.

  4. Host age only partially affects resistance to primary and secondary infections with Ascaridia galli (Schrank, 1788) in chickens.

    PubMed

    Idi, A; Permin, A; Murrell, K D

    2004-07-14

    Two experiments were conducted to compare the effect of chickens' age on resistance to primary and secondary infections with Ascaridia galli. In Experiment I, three groups, each of 80 female Lohman Brown chickens, aged one day, one month, or four months were compared. Within each group, 54 chickens were infected orally with 500 embryonated eggs and 26 were kept as non-infected controls. Weights were recorded weekly and five chickens in each group were slaughtered every 2 weeks for worm counts. At week 10 post-infection, 17 of the infected chickens and 18 of the controls were challenged with 500 eggs. In a replicate experiment (Experiment II), 35 one-day-old and 53 one-month-old female Lohman Brown chickens were infected orally with 500 A. galli eggs. Weights and fecal egg counts were recorded every week and infected chickens were necropsied every two weeks for determination of the worm burden. Chickens infected at one month of age excreted significantly fewer A. galli eggs when measured at 14 weeks of inoculation. The worms recovered from the one-month-old age group were significantly shorter than those from the chickens infected at one day of age in the first experiment. Worm burden and female fecundity values, however, were not significantly different between age groups in both Experiments I and II. Weight gains of infected chickens were not significantly different from the controls' and only a few chickens exhibited occasional slight diarrhea in both experiments. The results from these experiments demonstrate that the chickens' age only partially influences resistance to A. galli infection. PMID:15219363

  5. MURINE CYTOMEGALOVIRUS HOST RESISTANCE MODELS

    EPA Science Inventory

    Mouse cytomegalovirus (MCMV) is a well developed and extremely useful and relevant host resistance model for immunotoxicity testing. at cytomegalovirus (RCMV) is currently under development and may have similar applications. ytomegaloviruses are species specific; RCMV is a distin...

  6. Genetic diversity and insecticide resistance during the growing season in the green peach aphid (Hemiptera: Aphididae) on primary and secondary hosts: a farm-scale study in Central Chile.

    PubMed

    Rubiano-Rodríguez, J A; Fuentes-Contreras, E; Figueroa, C C; Margaritopoulos, J T; Briones, L M; Ramírez, C C

    2014-04-01

    The seasonal dynamics of neutral genetic diversity and the insecticide resistance mechanisms of insect pests at the farm scale are still poorly documented. Here this was addressed in the green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) in Central Chile. Samples were collected from an insecticide sprayed peach (Prunus persica L.) orchard (primary host), and a sweet-pepper (Capsicum annum var. grossum L.) field (secondary host). In addition, aphids from weeds (secondary hosts) growing among these crops were also sampled. Many unique multilocus genotypes were found on peach trees, while secondary hosts were colonized mostly by the six most common genotypes, which were predominantly sensitive to insecticides. In both fields, a small but significant genetic differentiation was found between aphids on the crops vs. their weeds. Within-season comparisons showed genetic differentiation between early and late season samples from peach, as well as for weeds in the peach orchard. The knock-down resistance (kdr) mutation was detected mostly in the heterozygote state, often associated with modified acetylcholinesterase throughout the season for both crops. This mutation was found in high frequency, mainly in the peach orchard. The super-kdr mutation was found in very low frequencies in both crops. This study provides farm-scale evidence that the aphid M. persicae can be composed of slightly different genetic groups between contiguous populations of primary and secondary hosts exhibiting different dynamics of insecticide resistance through the growing season. PMID:24484894

  7. Parasite host range and the evolution of host resistance.

    PubMed

    Gorter, F A; Hall, A R; Buckling, A; Scanlan, P D

    2015-05-01

    Parasite host range plays a pivotal role in the evolution and ecology of hosts and the emergence of infectious disease. Although the factors that promote host range and the epidemiological consequences of variation in host range are relatively well characterized, the effect of parasite host range on host resistance evolution is less well understood. In this study, we tested the impact of parasite host range on host resistance evolution. To do so, we used the host bacterium Pseudomonas fluorescens SBW25 and a diverse suite of coevolved viral parasites (lytic bacteriophage Φ2) with variable host ranges (defined here as the number of host genotypes that can be infected) as our experimental model organisms. Our results show that resistance evolution to coevolved phages occurred at a much lower rate than to ancestral phage (approximately 50% vs. 100%), but the host range of coevolved phages did not influence the likelihood of resistance evolution. We also show that the host range of both single parasites and populations of parasites does not affect the breadth of the resulting resistance range in a naïve host but that hosts that evolve resistance to single parasites are more likely to resist other (genetically) more closely related parasites as a correlated response. These findings have important implications for our understanding of resistance evolution in natural populations of bacteria and viruses and other host-parasite combinations with similar underlying infection genetics, as well as the development of phage therapy. PMID:25851735

  8. Host selection by the autoparasitoid Encarsia pergandiella on primary (Bemisia tabaci) and secondary (Eretmocerus mundus) hosts.

    PubMed

    Zhang, Yi-Bo; Castañé, Cristina; Gabarra, Rosa; Albajes, Ramon; Wan, Fang-Hao

    2015-12-01

    In autoparasitoids, females are generally primary endoparasitoids of Hemiptera, while males are hyperparasitoids developing in or on conspecific females or other primary parasitoids. Female-host acceptance can be influenced by extrinsic and/or intrinsic factors. In this paper, we are concerned with intrinsic factors such as nutritional status, mating status, etc. We observed the behavior of Encarsia pergandiella Howard (Hymenoptera: Aphelinidae) females when parasitizing primary (3rd instar larvae of Bemisia tabaci Gennadius [Homoptera: Aleyrodidae]) and secondary hosts (3rd instar larvae and pupae of Eretmocerus mundus Mercet [Hymenoptera: Aphelinidae]) for a period of 1 h. Females had different reproductive (virgin or mated younger) and physiological (fed elder or mated elder) status. Virgin females killed a large number of secondary hosts while investing a long time per host. However, they did not feed upon them. Mated females killed a lower number of secondary hosts and host feeding was observed in both consuming primary and secondary hosts. It was common to observe host examining females of all physiological statues tested repeatedly stinging the same hosts when parasitizing, killing or rejecting them. Fed elder females parasitized more B. tabaci larvae than E. mundus larvae or pupae, while investing less time on the primary host than on the secondary host. They also parasitized more B. tabaci larvae than mated elder females, while investing less time per host. The access of females to honey allowed them to lay more eggs. PMID:24992443

  9. Host factors governing resistance to Rhizoctonia solani

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the state of Washington, USA, annual losses of wheat attributed to soilborne necrotrophic fungal pathogens, such as Rhizoctonia solani, are estimated to be over US$100 million, and global estimates exceed US$1 billion. Host genetic resistance is a sustainable means of disease control that can be ...

  10. Inhibition of host resistance by nutritional hypercholesteremia.

    PubMed Central

    Kos, W L; Loria, R M; Snodgrass, M J; Cohen, D; Thorpe, T G; Kaplan, A M

    1979-01-01

    Previous experiments showed that nutritionally induced hypercholesteremia in mice caused an increase in susceptibility to coxsackievirus B, with a marked suppression of cellular infiltrates in infected tissues and an increased mortality. The present studies demonstrated that a hypercholesteremic diet was associated with an inhibition in host resistance as measured by susceptibility to Listeria monocytogenes infection and the growth of two transplanted syngeneic murine tumors. Moreover, the ability of Corynebacterium parvum to induce regression of a transplanted methylcholanthrene-induced fibrosarcoma was inhibited in hypercholesteremic hosts, as was the histiocytic infiltration normally accompanying C. parvum inoculation. In contrast, the peritoneal macrophages from C. parvum-treated hypercholesteremic mice were indistinguishable from similarly treated macrophages from normal mice with respect to their in vitro tumoricidal activity and the presence of a cell surface antigen associated with activated macrophages. Hypercholesteremia was also associated with a decreased antibody response to sheep erythrocytes in vivo, but dit not appear to exert a detrimental effect on B- or T-cell blastogenesis when tested in vitro. The findings that the hypercholesteremic diet was associated with an impairment in the host immune response and increased susceptibility to viral, bacterial, and tumor cell challenge are discussed with respect to virus-lipid interactions in the pathogenesis of atherogenesis and diabetes mellitus. Images PMID:317596

  11. Host versus nonhost resistance: distinct wars with similar arsenals.

    PubMed

    Gill, Upinder S; Lee, Seonghee; Mysore, Kirankumar S

    2015-05-01

    Plants face several challenges by bacterial, fungal, oomycete, and viral pathogens during their life cycle. In order to defend against these biotic stresses, plants possess a dynamic, innate, natural immune system that efficiently detects potential pathogens and initiates a resistance response in the form of basal resistance and/or resistance (R)-gene-mediated defense, which is often associated with a hypersensitive response. Depending upon the nature of plant-pathogen interactions, plants generally have two main defense mechanisms, host resistance and nonhost resistance. Host resistance is generally controlled by single R genes and less durable compared with nonhost resistance. In contrast, nonhost resistance is believed to be a multi-gene trait and more durable. In this review, we describe the mechanisms of host and nonhost resistance against fungal and bacterial plant pathogens. In addition, we also attempt to compare host and nonhost resistance responses to identify similarities and differences, and their practical applications in crop improvement. PMID:25626072

  12. The Role of Primary and Secondary Infection in Host Response to Plasmodiophora brassicae.

    PubMed

    McDonald, Mary Ruth; Sharma, Kalpana; Gossen, Bruce D; Deora, Abhinandan; Feng, Jie; Hwang, Sheau-Fang

    2014-10-01

    ABSTRACT The disease cycle of Plasmodiophora brassicae consists of a primary phase in root hairs followed by a secondary phase in the root cortex and adjacent tissues. However, the role of root hair infection in subsequent cortical infection and development of P. brassicae is not well understood. To examine the role of the primary and secondary stages separately, inoculation studies with resting spores (source of primary zoospores) and secondary zoospores of a virulent and avirulent pathotype were conducted on canola (Brassica napus). The size of secondary zoospores and number of nuclei were also examined. The zoospores were larger (≈9.6 to 14.4 μm) than in previous reports and all were uninucleate. Inoculation with secondary zoospores alone produced both primary and secondary infection, even with the avirulent pathotype. No symptoms developed from inoculation with avirulent primary zoospores but tiny, bead-shaped clubs developed from inoculation with avirulent secondary zoospores. Inoculation with virulent secondary zoospores alone resulted in lower disease severity than inoculation with virulent resting spores alone. The results indicate that recognition of infection by the host and initiation of a response (induction or suppression of resistance) occurs during primary infection, although recognition can also occur during cortical infection and development. PMID:24655290

  13. Resistant and susceptible responses of cereal hosts to aphid feeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although cereal host resistance to aphids has been examined extensively, little information is available on etiology of aphid injury and biochemical responses of resistant and susceptible cereal hosts to aphid feeding. Our team examined both aphid and plant factors for the Russian wheat aphid (RWA)...

  14. Dynamics of Mycobacteriophage-Mycobacterial Host Interaction: Evidence for Secondary Mechanisms for Host Lethality

    PubMed Central

    Samaddar, Sourabh; Grewal, Rajdeep Kaur; Sinha, Saptarshi; Ghosh, Shrestha

    2015-01-01

    Mycobacteriophages infect mycobacteria, resulting in their death. Therefore, the possibility of using them as therapeutic agents against the deadly mycobacterial disease tuberculosis (TB) is of great interest. To obtain better insight into the dynamics of mycobacterial inactivation by mycobacteriophages, this study was initiated using mycobacteriophage D29 and Mycobacterium smegmatis as the phage-host system. Here, we implemented a goal-oriented iterative cycle of experiments on one hand and mathematical modeling combined with Monte Carlo simulations on the other. This integrative approach lends valuable insight into the detailed kinetics of bacterium-phage interactions. We measured time-dependent changes in host viability during the growth of phage D29 in M. smegmatis at different multiplicities of infection (MOI). The predictions emerging out of theoretical analyses were further examined using biochemical and cell biological assays. In a phage-host interaction system where multiple rounds of infection are allowed to take place, cell counts drop more rapidly than expected if cell lysis is considered the only mechanism for cell death. The phenomenon could be explained by considering a secondary factor for cell death in addition to lysis. Further investigations reveal that phage infection leads to the increased production of superoxide radicals, which appears to be the secondary factor. Therefore, mycobacteriophage D29 can function as an effective antimycobacterial agent, the killing potential of which may be amplified through secondary mechanisms. PMID:26475112

  15. ASSESSMENT OF HOST RESISTANCE TO INFECTION WITH RODENT MALARIA

    EPA Science Inventory

    Resistance to malaria infection is known to require an intact immune system. his chapter presents an overview of rodent malaria, the host response to infection and methods for assessing infection in rats and mice.

  16. Adaptation to resistant hosts increases fitness on susceptible hosts in the plant parasitic nematode Globodera pallida.

    PubMed

    Fournet, Sylvain; Eoche-Bosy, Delphine; Renault, Lionel; Hamelin, Frédéric M; Montarry, Josselin

    2016-04-01

    Trade-offs between virulence (defined as the ability to infect a resistant host) and life-history traits are of particular interest in plant pathogens for durable management of plant resistances. Adaptation to plant resistances (i.e., virulence acquisition) is indeed expected to be associated with a fitness cost on susceptible hosts. Here, we investigated whether life-history traits involved in the fitness of the potato cyst nematode Globodera pallida are affected in a virulent lineage compared to an avirulent one. Both lineages were obtained from the same natural population through experimental evolution on resistant and susceptible hosts, respectively. Unexpectedly, we found that virulent lineages were more fit than avirulent lineages on susceptible hosts: they produced bigger cysts, containing more larvae and hatching faster. We thus discuss possible reasons explaining why virulence did not spread into natural G. pallida populations. PMID:27066239

  17. Host plant resistance to parasitic weeds; recent progress and bottlenecks.

    PubMed

    Yoder, John I; Scholes, Julie D

    2010-08-01

    Parasitic witchweeds (Striga spp.) and broomrapes (Orobanche and Phelipanche spp.) directly invade the roots of crop plants connecting to the vascular system and abstracting nutrients and water. As a consequence they cause devastating losses in crop yield. Genetic resistance to parasitic weeds is a highly desirable component of any control strategy. Resistance to parasitic plants can occur at different stages of the parasite lifecycle: before attachment to the host, during penetration of the root or after establishment of vascular connections. New studies are beginning to shed light on the molecular mechanisms and signaling pathways involved in plant-plant resistance. The first resistance gene to Striga, encoding a CC-NBS-LRR Resistance protein (R) has been identified and cloned suggesting that host plants resist attack from parasitic plants using similar surveillance mechanisms as those used against fungal and bacterial pathogens. It is becoming clear that the salicylic acid (SA) signaling pathway plays an important role in resistance to parasitic plants and genes encoding pathogenesis-related (PR) proteins are upregulated in a number of the resistant interactions. New strategies for engineering resistance to parasitic plants are also being explored, including the expression of parasite-specific toxins in host roots and RNAi to silence parasite genes crucial for development. PMID:20627804

  18. Host life history and host-parasite syntopy predict behavioural resistance and tolerance of parasites.

    PubMed

    Sears, Brittany F; Snyder, Paul W; Rohr, Jason R

    2015-05-01

    There is growing interest in the role that life-history traits of hosts, such as their 'pace-of-life', play in the evolution of resistance and tolerance to parasites. Theory suggests that, relative to host species that have high syntopy (local spatial and temporal overlap) with parasites, host species with low syntopy should have lower selection pressures for more constitutive (always present) and costly defences, such as tolerance, and greater reliance on more inducible and cheaper defences, such as behaviour. Consequently, we postulated that the degree of host-parasite syntopy, which is negatively correlated with host pace-of-life (an axis reflecting the developmental rate of tadpoles and the inverse of their size at metamorphosis) in our tadpole-parasitic cercarial (trematode) system, would be a negative and positive predictor of behavioural resistance and tolerance, respectively. To test these hypotheses, we exposed seven tadpole species to a range of parasite (cercarial) doses crossed with anaesthesia treatments that controlled for anti-parasite behaviour. We quantified host behaviour, successful and unsuccessful infections, and each species' reaction norm for behavioural resistance and tolerance, defined as the slope between cercarial exposure (or attempted infections) and anti-cercarial behaviours and mass change, respectively. Hence, tolerance is capturing any cost of parasite exposure. As hypothesized, tadpole pace-of-life was a significant positive predictor of behavioural resistance and negative predictor of tolerance, a result that is consistent with a trade-off between behavioural resistance and tolerance across species that warrants further investigation. Moreover, these results were robust to considerations of phylogeny, all possible re-orderings of the three fastest or slowest paced species, and various measurements of tolerance. These results suggest that host pace-of-life and host-parasite syntopy are powerful drivers of both the strength and type

  19. Interferon-Inducible GTPases in Host Resistance, Inflammation and Disease.

    PubMed

    Pilla-Moffett, Danielle; Barber, Matthew F; Taylor, Gregory A; Coers, Jörn

    2016-08-28

    Cell-autonomous immunity is essential for host organisms to defend themselves against invasive microbes. In vertebrates, both the adaptive and the innate branches of the immune system operate cell-autonomous defenses as key effector mechanisms that are induced by pro-inflammatory interferons (IFNs). IFNs can activate cell-intrinsic host defenses in virtually any cell type ranging from professional phagocytes to mucosal epithelial cells. Much of this IFN-induced host resistance program is dependent on four families of IFN-inducible GTPases: the myxovirus resistance proteins, the immunity-related GTPases, the guanylate-binding proteins (GBPs), and the very large IFN-inducible GTPases. These GTPase families provide host resistance to a variety of viral, bacterial, and protozoan pathogens through the sequestration of microbial proteins, manipulation of vesicle trafficking, regulation of antimicrobial autophagy (xenophagy), execution of intracellular membranolytic pathways, and the activation of inflammasomes. This review discusses our current knowledge of the molecular function of IFN-inducible GTPases in providing host resistance, as well as their role in the pathogenesis of autoinflammatory Crohn's disease. While substantial advances were made in the recent past, few of the known functions of IFN-inducible GTPases have been explored in any depth, and new functions await discovery. This review will therefore highlight key areas of future exploration that promise to advance our understanding of the role of IFN-inducible GTPases in human diseases. PMID:27181197

  20. The molecular pathways underlying host resistance and tolerance to pathogens

    PubMed Central

    Glass, Elizabeth J.

    2012-01-01

    Breeding livestock that are better able to withstand the onslaught of endemic- and exotic pathogens is high on the wish list of breeders and farmers world-wide. However, the defense systems in both pathogens and their hosts are complex and the degree of genetic variation in resistance and tolerance will depend on the trade-offs that they impose on host fitness as well as their life-histories. The genes and pathways underpinning resistance and tolerance traits may be distinct or intertwined as the outcome of any infection is a result of a balance between collateral damage of host tissues and control of the invading pathogen. Genes and molecular pathways associated with resistance are mainly expressed in the mucosal tract and the innate immune system and control the very early events following pathogen invasion. Resistance genes encode receptors involved in uptake of pathogens, as well as pattern recognition receptors (PRR) such as the toll-like receptor family as well as molecules involved in strong and rapid inflammatory responses which lead to rapid pathogen clearance, yet do not lead to immunopathology. In contrast tolerance genes and pathways play a role in reducing immunopathology or enhancing the host's ability to protect against pathogen associated toxins. Candidate tolerance genes may include cytosolic PRRs and unidentified sensors of pathogen growth, perturbation of host metabolism and intrinsic danger or damage associated molecules. In addition, genes controlling regulatory pathways, tissue repair and resolution are also tolerance candidates. The identities of distinct genetic loci for resistance and tolerance to infectious pathogens in livestock species remain to be determined. A better understanding of the mechanisms involved and phenotypes associated with resistance and tolerance should ultimately help to improve livestock health and welfare. PMID:23403960

  1. Screening for Host Plant Resistance to Azalea Lace Bug

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Azalea Lace bug (ALB) are a major pest of azaleas in the southeast. Adults and nymphs cause visible damage on the upper leaf surface. Host plant resistance to ALB provides “built-in” plant protection and allows for reduced dependency on pesticide applications for both growers and consumers. We have...

  2. Addicted? Reduced host resistance in populations with defensive symbionts.

    PubMed

    Martinez, Julien; Cogni, Rodrigo; Cao, Chuan; Smith, Sophie; Illingworth, Christopher J R; Jiggins, Francis M

    2016-06-29

    Heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. By reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. Therefore, the presence of such symbionts may slow down the evolution of resistance. Here we investigated this idea by exposing Drosophila melanogaster populations to infection with the pathogenic Drosophila C virus (DCV) in the presence or absence of Wolbachia, a heritable symbiont of arthropods that confers protection against viruses. After nine generations of selection, we found that resistance to DCV had increased in all populations. However, in the presence of Wolbachia the resistant allele of pastrel-a gene that has a major effect on resistance to DCV-was at a lower frequency than in the symbiont-free populations. This finding suggests that defensive symbionts have the potential to hamper the evolution of insect resistance genes, potentially leading to a state of evolutionary addiction where the genetically susceptible insect host mostly relies on its symbiont to fight pathogens. PMID:27335421

  3. Addicted? Reduced host resistance in populations with defensive symbionts

    PubMed Central

    Cogni, Rodrigo; Cao, Chuan; Smith, Sophie; Illingworth, Christopher J. R.; Jiggins, Francis M.

    2016-01-01

    Heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. By reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. Therefore, the presence of such symbionts may slow down the evolution of resistance. Here we investigated this idea by exposing Drosophila melanogaster populations to infection with the pathogenic Drosophila C virus (DCV) in the presence or absence of Wolbachia, a heritable symbiont of arthropods that confers protection against viruses. After nine generations of selection, we found that resistance to DCV had increased in all populations. However, in the presence of Wolbachia the resistant allele of pastrel—a gene that has a major effect on resistance to DCV—was at a lower frequency than in the symbiont-free populations. This finding suggests that defensive symbionts have the potential to hamper the evolution of insect resistance genes, potentially leading to a state of evolutionary addiction where the genetically susceptible insect host mostly relies on its symbiont to fight pathogens. PMID:27335421

  4. A latitudinal cline in disease resistance of a host tree

    PubMed Central

    Hamilton, M G; Williams, D R; Tilyard, P A; Pinkard, E A; Wardlaw, T J; Glen, M; Vaillancourt, R E; Potts, B M

    2013-01-01

    The possible drivers and implications of an observed latitudinal cline in disease resistance of a host tree were examined. Mycosphaerella leaf disease (MLD) damage, caused by Teratosphaeria species, was assessed in five Eucalyptus globulus (Tasmanian blue gum) common garden trials containing open-pollinated progeny from 13 native-forest populations. Significant population and family within population variation in MLD resistance was detected, which was relatively stable across different combinations of trial sites, ages, seasons and epidemics. A distinct genetic-based latitudinal cline in MLD damage among host populations was evident. Two lines of evidence argue that the observed genetic-based latitudinal trend was the result of direct pathogen-imposed selection for MLD resistance. First, MLD damage was positively associated with temperature and negatively associated with a prediction of disease risk in the native environment of these populations; and, second, the quantitative inbreeding coefficient (QST) significantly exceeded neutral marker FST at the trial that exhibited the greatest MLD damage, suggesting that diversifying selection contributed to differentiation in MLD resistance among populations. This study highlights the potential for spatial variation in pathogen risk to drive adaptive differentiation across the geographic range of a foundation host tree species. PMID:23211794

  5. Common Secondary Causes of Resistant Hypertension and Rational for Treatment

    PubMed Central

    Faselis, Charles; Doumas, Michael; Papademetriou, Vasilios

    2011-01-01

    Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of resistant hypertension. Several drugs can induce or exacerbate pre-existing hypertension, with non-steroidal anti-inflammatory drugs being the most common due to their wide use. Obstructive sleep apnoea and primary aldosteronism are frequently encountered in patients with resistant hypertension and require expert management. Hypertension is commonly found in patients with chronic kidney disease and is frequently resistant to treatment, while the management of renovascular hypertension remains controversial. A step-by-step approach of patients with resistant hypertension is proposed at the end of this review paper. PMID:21423678

  6. Host use of a specialist lichen-feeder: dealing with lichen secondary metabolites.

    PubMed

    Pöykkö, Heikki; Backor, Martin; Bencúrová, Elena; Molcanová, Viktoria; Backorová, Miriam; Hyvärinen, Marko

    2010-10-01

    Host use by herbivores is largely determined by host properties such as nutrient content and chemical defence against foragers. The impacts of these attributes on a herbivore may largely depend on its life cycle stage. Lichen species are known to differ in nutritional quality and level of chemical defence and, consequently, vary as fodder for herbivores. The aim of this study was to explore the impact of several lichen species and the presence of their secondary metabolites on their use as hosts by a specialist lichen-feeder, Cleorodes lichenaria. This study also addressed, for the first time, how a specialist lichen-feeder deals with different lichen secondary metabolites. In the beginning of their development, larvae grew better on Xanthoria parietina than on the other host lichens, whereas older larvae grew best on Ramalina fraxinea. Lichen secondary chemicals in R. fraxinea and Parmelia sulcata hindered larval growth in the beginning but after 75 days lichen secondary chemicals had no impact on the mass of larvae. Physodic acids in Hypogymnia physodes were lethal to larvae. In general, larvae metabolized 70-95% of ingested lichen secondary chemicals and the rest of these were excreted in frass. Lichen secondary metabolites in P. sulcata restrict and in H. physodes prevent their use as a host for C. lichenaria larvae. Our main finding, the ability of larvae to metabolize several lichen secondary metabolites, indicates digestive adaptation to these chemicals. No signs of sequestration of these chemicals were found. PMID:20585810

  7. The host model Galleria mellonella is resistant to taylorellae infection.

    PubMed

    Hébert, L; Rincé, I; Sanna, C; Laugier, C; Rincé, A; Petry, S

    2014-10-01

    The genus Taylorella is composed of two species: (i) Taylorella equigenitalis, the causative agent of CEM, a venereally transmitted infection of Equidae and (ii) Taylorella asinigenitalis, a closely related species considered to be nonpathogenic, although experimental infection of mares with this bacterium resulted in clinical signs of vaginitis, cervicitis or endometritis. Currently, there is a need for an alternative host model to further study the taylorellae species. In this context, we explored Galleria mellonella larvae as potential alternative model hosts for taylorellae. Our results showed that infection of G. mellonella larvae with a high concentration of taylorellae did not induce overt G. mellonella mortality and that taylorellae were not able to proliferate within G. mellonella. In conclusion, G. mellonella larvae are resistant to taylorellae infection and therefore do not constitute a relevant alternative system for studying the virulence of taylorellae species. Significance and impact of the study: To date, the pathogenicity and host colonization capacity of Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM) and T. asinigenitalis, the second species within the Taylorella genus, remain largely unknown. In this study, we evaluated the relevance of Galleria mellonella as an infection model for taylorellae; we showed that G. mellonella are resistant to taylorellae infection and therefore do not constitute a suitable host model for taylorellae. PMID:24945970

  8. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance

    PubMed Central

    Trapero, Carlos; Wilson, Iain W.; Stiller, Warwick N.; Wilson, Lewis J.

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars. PMID:27148323

  9. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance.

    PubMed

    Trapero, Carlos; Wilson, Iain W; Stiller, Warwick N; Wilson, Lewis J

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars. PMID:27148323

  10. Associations between host characteristics and antimicrobial resistance of Salmonella typhimurium.

    PubMed

    Ruddat, I; Tietze, E; Ziehm, D; Kreienbrock, L

    2014-10-01

    A collection of Salmonella Typhimurium isolates obtained from sporadic salmonellosis cases in humans from Lower Saxony, Germany between June 2008 and May 2010 was used to perform an exploratory risk-factor analysis on antimicrobial resistance (AMR) using comprehensive host information on sociodemographic attributes, medical history, food habits and animal contact. Multivariate resistance profiles of minimum inhibitory concentrations for 13 antimicrobial agents were analysed using a non-parametric approach with multifactorial models adjusted for phage types. Statistically significant associations were observed for consumption of antimicrobial agents, region type and three factors on egg-purchasing behaviour, indicating that besides antimicrobial use the proximity to other community members, health consciousness and other lifestyle-related attributes may play a role in the dissemination of resistances. Furthermore, a statistically significant increase in AMR from the first study year to the second year was observed. PMID:24300336

  11. Sugarcane Aphid (Hemiptera: Aphididae): Host Range and Sorghum Resistance Including Cross-Resistance From Greenbug Sources.

    PubMed

    Armstrong, J Scott; Rooney, William L; Peterson, Gary C; Villenueva, Raul T; Brewer, Michael J; Sekula-Ortiz, Danielle

    2015-04-01

    The graminous host range and sources of sorghum [Sorghum bicolor (L.) Moench.] plant resistance, including cross-resistance from greenbug, Schizaphis graminum (Rondani), were studied for the newly emerging sugarcane aphid, Melanaphis sacchari (Zehntner), in greenhouse no-choice experiments and field evaluations. The sugarcane aphid could not survive on field corn, Zea mays (L.), Teff grass, Eragrostis tef (Zucc.), proso millet, Panicum miliaceum L., barley, Hordeum vulgare L., and rye, Secale cereale L. Only sorghum genotypes served as hosts including Johnsongrass, Sorghum halepense (L.), a highly suitable noncrop host that generates high numbers of sugarcane aphid and maintains moderate phenotypic injury. The greenbug-resistant parental line RTx2783 that is resistant to greenbug biotypes C and E was resistant to sugarcane aphid in both greenhouse and field tests, while PI 55607 greenbug resistant to biotypes B, C, and E was highly susceptible. PI 55610 that is greenbug resistant to biotypes B, C, and E maintained moderate resistance to the sugarcane aphid, while greenbug-resistant PI 264453 was highly susceptible to sugarcane aphid. Two lines and two hybrids from the Texas A&M breeding program B11070, B11070, AB11055-WF1-CS1/RTx436, and AB11055-WF1-CS1/RTx437 were highly resistant to sugarcane aphid, as were parental types SC110, SC170, and South African lines Ent62/SADC, (Macia/TAM428)-LL9, (SV1*Sima/IS23250)-LG15. Tam428, a parental line that previously showed moderate resistance in South Africa and India, also showed moderate resistance in these evaluations. Overall, 9 of 20 parental sorghum entries tested for phenotypic damage in the field resulted in good resistance to the sugarcane aphid and should be utilized in breeding programs that develop agronomically acceptable sorghums for the southern regions of the United States. PMID:26470168

  12. Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection

    PubMed Central

    Lee, Heather; Prince, Jessica; Stadnisky, Michael D.; Anderson, Monique; Nash, William; Rival, Claudia; Wei, Hairong; Gamache, Awndre; Farber, Charles R.; Tung, Kenneth; Brown, Michael G.

    2016-01-01

    The MHC class I Dk molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds Dk, are required to control viral spread. The extent of Dk-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust Dk-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen. PMID:26845690

  13. Development of a solitary koinobiont hyperparasitoid in different instars of its primary and secondary hosts.

    PubMed

    Harvey, Jeffrey A; Fei, Minghui; Lammers, Mark; Kos, Martine; Zhu, Feng; Heinen, Robin; Poelman, Erik H; Gols, Rieta

    2016-07-01

    Parasitoid wasps are excellent organisms for studying the allocation of host resources to different fitness functions such as adult body mass and development time. Koinobiont parasitoids attack hosts that continue feeding and growing during parasitism, whereas idiobiont parasitoids attack non-growing host stages or paralyzed hosts. Many adult female koinobionts attack a broad range of host stages and are therefore faced with a different set of dynamic challenges compared with idiobionts, where host resources are largely static. Thus far studies on solitary koinobionts have been almost exclusively based on primary parasitoids, yet it is known that many of these are in turn attacked by both koinobiont and idiobiont hyperparasitoids. Here we compare parasitism and development of a primary koinobiont hyperparasitoid, Mesochorus gemellus (Hymenoptera: Ichneumonidae) in larvae of the gregarious primary koinobiont parasitoid, Cotesia glomerata (Hymenoptera: Braconidae) developing in the secondary herbivore host, Pieris brassicae (Lepidoptera: Pieridae). As far as we know this is the first study to examine development of a solitary primary hyperparasitoid in different stages of its secondary herbivore host. Pieris brassicae caterpillars were parasitized as L1 by C. glomerata and then these parasitized caterpillars were presented in separate cohorts to M. gemellus as L3, L4 or L5 instar P. brassicae. Different instars of the secondary hosts were used as proxies for different developmental stages of the primary host, C. glomerata. Larvae of C. glomerata in L5 P. brassicae were significantly longer than those in L3 and L4 caterpillars. Irrespective of secondary host instar, every parasitoid cluster was hyperparasitized by M. gemellus but all only produced male progeny. Male development time decreased with host stage attacked, whereas adult male body mass did not, which shows that M. gemellus is able to optimally exploit older host larvae in terms of adult size despite their

  14. Heterologous Expression of Fungal Secondary Metabolite Pathways in the Aspergillus nidulans Host System.

    PubMed

    van Dijk, J W A; Wang, C C C

    2016-01-01

    Heterologous expression of fungal secondary metabolite genes allows for the product formation of otherwise silent secondary metabolite biosynthesis pathways. It also allows facile expression of mutants or combinations of genes not found in nature. This capability makes model fungi an ideal platform for synthetic biology. In this chapter a detailed description is provided of how to heterologously express any fungal secondary metabolite gene(s) in a well-developed host strain of Aspergillus nidulans. It covers all the necessary steps from identifying a gene(s) of interest to culturing mutant strains to produce secondary metabolites. PMID:27417927

  15. A combined within-host and between-hosts modelling framework for the evolution of resistance to antimalarial drugs.

    PubMed

    Legros, Mathieu; Bonhoeffer, Sebastian

    2016-04-01

    The spread of drug resistance represents a significant challenge to many disease control efforts. The evolution of resistance is a complex process influenced by transmission dynamics between hosts as well as infection dynamics within these hosts. This study aims to investigate how these two processes combine to impact the evolution of resistance in malaria parasites. We introduce a stochastic modelling framework combining an epidemiological model of Plasmodium transmission and an explicit within-human infection model for two competing strains. Immunity, treatment and resistance costs are included in the within-host model. We show that the spread of resistance is generally less likely in areas of intense transmission, and therefore of increased competition between strains, an effect exacerbated when costs of resistance are higher. We also illustrate how treatment influences the spread of resistance, with a trade-off between slowing resistance and curbing disease incidence. We show that treatment coverage has a stronger impact on disease prevalence, whereas treatment efficacy primarily affects resistance spread, suggesting that coverage should constitute the primary focus of control efforts. Finally, we illustrate the importance of feedbacks between modelling scales. Overall, our results underline the importance of concomitantly modelling the evolution of resistance within and between hosts. PMID:27075004

  16. A combined within-host and between-hosts modelling framework for the evolution of resistance to antimalarial drugs

    PubMed Central

    2016-01-01

    The spread of drug resistance represents a significant challenge to many disease control efforts. The evolution of resistance is a complex process influenced by transmission dynamics between hosts as well as infection dynamics within these hosts. This study aims to investigate how these two processes combine to impact the evolution of resistance in malaria parasites. We introduce a stochastic modelling framework combining an epidemiological model of Plasmodium transmission and an explicit within-human infection model for two competing strains. Immunity, treatment and resistance costs are included in the within-host model. We show that the spread of resistance is generally less likely in areas of intense transmission, and therefore of increased competition between strains, an effect exacerbated when costs of resistance are higher. We also illustrate how treatment influences the spread of resistance, with a trade-off between slowing resistance and curbing disease incidence. We show that treatment coverage has a stronger impact on disease prevalence, whereas treatment efficacy primarily affects resistance spread, suggesting that coverage should constitute the primary focus of control efforts. Finally, we illustrate the importance of feedbacks between modelling scales. Overall, our results underline the importance of concomitantly modelling the evolution of resistance within and between hosts. PMID:27075004

  17. The Role of Viral, Host, and Secondary Bacterial Factors in Influenza Pathogenesis

    PubMed Central

    Kash, John C.; Taubenberger, Jeffery K.

    2016-01-01

    Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza. PMID:25747532

  18. Honey bee fungal pathogen, Ascosphaera apis; current understanding of host-pathogen interactions and host mechanisms of resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter provides an overview of the profound knowledge accumulated in recent years from genome and transcriptome-wide attempts to determine host immune responses to honey bee fungal diseases and to identify quantitative trait loci (QTLs) that underline host mechanisms of resistance. Considering...

  19. Differential temporal changes of primary and secondary bacterial symbionts and whitefly host fitness following antibiotic treatments.

    PubMed

    Zhang, Chang-Rong; Shan, Hong-Wei; Xiao, Na; Zhang, Fan-Di; Wang, Xiao-Wei; Liu, Yin-Quan; Liu, Shu-Sheng

    2015-01-01

    Where multiple symbionts coexist in the same host, the selective elimination of a specific symbiont may enable the roles of a given symbiont to be investigated. We treated the Mediterranean species of the whitefly Bemisia tabaci complex by oral delivery of the antibiotic rifampicin, and then examined the temporal changes of its primary symbiont "Candidatus Portiera aleyrodidarum" and secondary symbiont "Ca. Hamiltonella defensa" as well as host fitness for three generations. In adults treated with rifampicin (F0), the secondary symbiont was rapidly reduced, approaching complete disappearance as adults aged. In contrast, the primary symbiont was little affected until later in the adult life. In the offspring of these adults (F1), both symbionts were significantly reduced and barely detectable when the hosts reached the adult stage. The F1 adults laid few eggs (F2), all of which failed to hatch. Mating experiments illustrated that the negative effects of rifampicin on host fitness were exerted via female hosts but not males. This study provides the first evidence of differential temporal reductions of primary and secondary symbionts in whiteflies following an antibiotic treatment. Studies that disrupt functions of bacterial symbionts must consider their temporal changes. PMID:26510682

  20. Differential temporal changes of primary and secondary bacterial symbionts and whitefly host fitness following antibiotic treatments

    PubMed Central

    Zhang, Chang-Rong; Shan, Hong-Wei; Xiao, Na; Zhang, Fan-Di; Wang, Xiao-Wei; Liu, Yin-Quan; Liu, Shu-Sheng

    2015-01-01

    Where multiple symbionts coexist in the same host, the selective elimination of a specific symbiont may enable the roles of a given symbiont to be investigated. We treated the Mediterranean species of the whitefly Bemisia tabaci complex by oral delivery of the antibiotic rifampicin, and then examined the temporal changes of its primary symbiont “Candidatus Portiera aleyrodidarum” and secondary symbiont “Ca. Hamiltonella defensa” as well as host fitness for three generations. In adults treated with rifampicin (F0), the secondary symbiont was rapidly reduced, approaching complete disappearance as adults aged. In contrast, the primary symbiont was little affected until later in the adult life. In the offspring of these adults (F1), both symbionts were significantly reduced and barely detectable when the hosts reached the adult stage. The F1 adults laid few eggs (F2), all of which failed to hatch. Mating experiments illustrated that the negative effects of rifampicin on host fitness were exerted via female hosts but not males. This study provides the first evidence of differential temporal reductions of primary and secondary symbionts in whiteflies following an antibiotic treatment. Studies that disrupt functions of bacterial symbionts must consider their temporal changes. PMID:26510682

  1. Intra-arterial Methylprednisolone Infusion in Treatment-Resistant Graft-Versus-Host Disease

    SciTech Connect

    Weintraub, Joshua L. Belanger, Adam R.; Sung, Chris C.; Stangl, P. Anondo; Nowakowski, F. Scott; Lookstein, Robert L.

    2010-06-15

    Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality. There is no generally accepted secondary therapy for acute GVHD. Although few data on localized therapy for GVHD have been published, intra-arterial injection of high-dose corticosteroids may be a viable option. We treated 11 patients with steroid-resistant GVHD using a single administration of intra-arterial high-dose methylprednisolone. Three patients (27%) died periprocedurally. Four patients (36%) had a partial response to intra-arterial treatment and were discharged on total parenteral nutrition and oral medication. Four patients (36%) had a complete response and were discharged on oral diet and oral medication. No immediate treatment or procedure-related complications were noted. Twenty-seven percent of patients survived long-term. Our preliminary results suggest that regional intra-arterial treatment of steroid-resistant GVHD is a safe and potentially viable secondary therapy in primary treatment-resistant GVHD.

  2. Host resistance to intranasal Acinetobacter baumannii reinfection in mice.

    PubMed

    Qiu, Hongyu; Li, Zack; KuoLee, Rhonda; Harris, Greg; Gao, Xiaoling; Yan, Hongbin; Xu, H Howard; Chen, Wangxue

    2016-07-01

    Acinetobacter baumannii is a major causative agent of healthcare-associated infection and develops multidrug resistance rapidly. However, little is known in the host defense mechanisms against this infection. In this study, we examined if mice recovered from a previous intranasal A. baumannii infection (recovered mice) are fully protected against a subsequent reinfection. We found that, despite the presence of specific serum IgG and mucosal IgA responses prior to the reinfection, the recovered mice were only marginally better protected against intranasal challenge with low doses of homologous or heterologous A. baumannii strains than the naïve mice. Post-challenge immune and inflammatory (cells and cytokines) responses were generally comparable between recovered and naïve mice although the recovered mice produced significantly higher amounts of IFN-γ and IL-17 and had higher percentages and numbers of resident lung CD44(hi)CD62L(-)CD4(+) and CD19(+) B lymphocytes. Taken together, our results suggest that mice recovered from a previous A. baumannii infection remain susceptible to reinfection, indicating the complexity of immune protection mechanism for this Gram-negative, multidrug-resistant emerging pathogen. PMID:27194730

  3. Mini Review: Potential Applications of Non-host Resistance for Crop Improvement.

    PubMed

    Lee, Seonghee; Whitaker, Vance M; Hutton, Samuel F

    2016-01-01

    Plant breeding for disease resistance is crucial to sustain global crop production. For decades, plant breeders and researchers have extensively used host plant resistance genes (R-genes) to develop disease resistant cultivars. However, the general instability of R-genes in crop cultivars when challenged with diverse pathogen populations emphasizes the need for more stable means of resistance. Alternatively, non-host resistance is recognized as the most durable, broad-spectrum form of resistance against the majority of potential pathogens in plants and has gained great attention as an alternative target for managing resistance. While transgenic approaches have been utilized to transfer non-host resistance to host species, conventional breeding applications have been more elusive. Nevertheless, avenues for discovery and deployment of genetic loci for non-host resistance via hybridization are increasingly abundant, particularly when transferring genes among closely related species. In this mini review, we discuss current and developing applications of non-host resistance for crop improvement with a focus on the overlap between host and non-host mechanisms and the potential impacts of new technology. PMID:27462329

  4. Mini Review: Potential Applications of Non-host Resistance for Crop Improvement

    PubMed Central

    Lee, Seonghee; Whitaker, Vance M.; Hutton, Samuel F.

    2016-01-01

    Plant breeding for disease resistance is crucial to sustain global crop production. For decades, plant breeders and researchers have extensively used host plant resistance genes (R-genes) to develop disease resistant cultivars. However, the general instability of R-genes in crop cultivars when challenged with diverse pathogen populations emphasizes the need for more stable means of resistance. Alternatively, non-host resistance is recognized as the most durable, broad-spectrum form of resistance against the majority of potential pathogens in plants and has gained great attention as an alternative target for managing resistance. While transgenic approaches have been utilized to transfer non-host resistance to host species, conventional breeding applications have been more elusive. Nevertheless, avenues for discovery and deployment of genetic loci for non-host resistance via hybridization are increasingly abundant, particularly when transferring genes among closely related species. In this mini review, we discuss current and developing applications of non-host resistance for crop improvement with a focus on the overlap between host and non-host mechanisms and the potential impacts of new technology. PMID:27462329

  5. Interspecific variation in resistance of two host tree species to spruce budworm

    NASA Astrophysics Data System (ADS)

    Fuentealba, Alvaro; Bauce, Éric

    2016-01-01

    Woody plants regularly sustain biomass losses to herbivorous insects. Consequently, they have developed various resistance mechanisms to cope with insect attack. However, these mechanisms of defense and how they are affected by resource availability are not well understood. The present study aimed at evaluating and comparing the natural resistance (antibiosis and tolerance) of balsam fir (Abies balsamea [L.] Mill.) and white spruce (Picea glauca [Moench) Voss] to spruce budworm, Choristoneura fumiferana (Clem.), and how drainage site quality as a component of resource availability affects the expression of resistance over time (6 years). Our results showed that there are differences in natural resistance between the two tree species to spruce budworm, but it was not significantly affected by drainage quality. Balsam fir exhibited higher foliar toxic secondary compounds concentrations than white spruce in all drainage classes, resulting in lower male pupal mass, survival and longer male developmental time. This, however, did not prevent spruce budworm from consuming more foliage in balsam fir than in white spruce. This response suggests that either natural levels of measured secondary compounds do not provide sufficient toxicity to reduce defoliation, or spruce budworm has developed compensatory mechanisms, which allow it to utilize food resources more efficiently or minimize the toxic effects that are produced by its host's defensive compounds. Larvae exhibited lower pupal mass and higher mortality in rapidly drained and subhygric sites. Drainage class also affected the amount of foliage destroyed but its impact varied over the years and was probably influenced by climatic variables. These results demonstrate the complexity of predicting the effect of resource availability on tree defenses, especially when other confounding environmental factors can affect tree resource allocation and utilization.

  6. Resistance to Arrenurus spp. Parasitism in Odonates: Patterns Across Species and Comparisons Between a Resistant and Susceptible Host

    PubMed Central

    Worthen, Wade B.

    2016-01-01

    Some adult odonates resist parasitism by larval water mites (Arrenurus spp.) with melanotic encapsulation, in which the mite’s stylestome is clogged and the mite starves. In summer 2014, we counted the engorged and resisted mites on 2,729 adult odonates sampled by aerial net at 11 water bodies in Greenville Co. and Pickens Co., SC, and tested the hypothesis that the frequency and intensity of resistance correlates with parasite prevalence (the percentage of parasitized hosts). Resistance prevalence (the percentage of parasitized hosts that resisted at least one mite) varied significantly among host species, exceeding 60% for Argia fumipennis (Burmeister) and Celithemis fasciata Kirby but less than 20% for other species. However, neither resistance prevalence nor mean resistance intensity (mean percentage of resisted mites on resisting hosts) correlated with parasite prevalence. We described potential effects of parasitism on host development of A. fumipennis and Pachydiplax longipennis (Burmeister) by comparing the percent asymmetry of forewing lengths between parasitized and unparasitized individuals. There was no significant difference in asymmetry for either males or females of A. fumipennis, or males of Pa. longipennis (females were not sampled). We also evaluated differences in melanotic encapsulation between A. fumipennis, which readily encapsulates mites in nature, and Pa. longipennis. We inserted a 2.0-mm piece of sterile monofilament line into the thorax of captured individuals for 24 h and compared mean gray value scores of inserted and emergent ends using Image-J software. There was no difference in melanotic encapsulation between species. PMID:27067302

  7. ERECTA contributes to non-host resistance to Magnaporthe oryzae in Arabidopsis.

    PubMed

    Takahashi, Toshiharu; Shibuya, Haruki; Ishikawa, Atsushi

    2016-07-01

    ERECTA controls both developmental processes and disease resistance in Arabidopsis. We investigated the function of ERECTA in non-host resistance to Magnaporthe oryzae in Arabidopsis. In the pen2 er mutant, penetration resistance and post-penetration resistance to M. oryzae were compromised. These results suggest that ERECTA is involved in both penetration and post-penetration resistance to M. oryzae in Arabidopsis. PMID:26924213

  8. Host resistance influences patterns of experimental viral adaptation and virulence evolution

    PubMed Central

    Kubinak, Jason L; Potts, Wayne K

    2013-01-01

    Infectious diseases are major threats to all living systems, so understanding the forces of selection that limit the evolution of more virulent pathogens is of fundamental importance; this includes the practical application of identifying possible mitigation strategies for at-risk host populations. The evolution of more virulent pathogens has been classically understood to be limited by the tradeoff between within-host growth rate and transmissibility. Importantly, heterogeneity among hosts can influence both of these factors. However, despite our substantial understanding of how the immune system operates to control pathogen replication during infection, we have only a limited appreciation of how variability in intrinsic (i.e., genetically determined) levels of host resistance influences patterns of pathogen adaptation and virulence evolution. Here, we describe results from experimental evolution studies using a model host–pathogen (virus–mammal) system; we demonstrate that variability in intrinsic levels of resistance among host genotypes can have significant effects on patterns of pathogen adaptation and virulence evolution during serial passage. Both the magnitude of adaptive response as well as the degree of pathogen specialization was positively correlated with host resistance, while mean overall virulence of post-passage virus was negatively correlated with host resistance. These results are consistent with a model whereby resistant host genotypes impose stronger selection on adapting pathogen populations, which in turn leads to the evolution of more specialized pathogen variants whose overall (i.e., mean) virulence across host genotypes is reduced. PMID:23645287

  9. Host resistance reflected in differential nematode population structures.

    PubMed

    Viglierchio, D R; Croll, N A

    1968-07-19

    Relative efficiency of host plants to support reproduction of the garlic race of Ditylenchus dipsaci can be partially explained by diflerential population structures. If axenic cultures of callus tissue from onion, white clover, red clover, and alfalfa are arranged in order of decreasing host suitability, the nematode populations are simultaneously arranged in order of increasing maleness. PMID:5657331

  10. Role of Myzus persicae (Hemiptera: Aphididae) and its secondary hosts in plum pox virus propagation.

    PubMed

    Manachini, B; Casati, P; Cinanni, L; Bianco, P

    2007-08-01

    Plum pox virus (family Potyviridae, genus Potyvirus, PPV) is one of the most important viral pathogens of plants in the genus Prunus, particularly Prunus persica L. The role of the Myzus persicae (Sulzer) (Hemiptera: Aphididae) as a vector of PPV-M, and its role in spreading PPV-M, was investigated. PPV-M-infected peach trees were used as inoculum sources, and transmission to 15 herbaceous species commonly present in and around peach orchards was evaluated. The presence of PPV-M in secondary hosts after aphid transmission was verified by reverse transcription-polymerase chain reaction tests. The results indicate that Saponaria ocymoides L., Pisum sativum L., Trifolium repens L., Trifolium pratense L., Lepidium sativum L., Matricaria chamomilla L., Centaurea cyanus L., Bellis perennis L., Papaver rhoeas L., and Zinnia elegans L. became infected. Although Lupinus polyphyllus Lindley, Taraxacum officinale L., Achillea millefolium L., Amaranthus retroflexus L., and Linum rubrum L. did not become infected, they are hosts of M. persicae. Among the 10 positive species that were infected, the species most common in peach orchards, T. pratense, T. repens, B. perennis, and M. chamomilla, were used as source plants for the transmission studies to the peach tree. Our study reveals the ability of M. persicae to transmit PPV-M from herbaceous hosts to peach trees, describes PPV-M symptoms in herbaceous species, and discusses the role of M. persicae and its hosts as a source of PPV-M in peach orchards. PMID:17849850

  11. Development of maize host resistance to aflatoxigenic fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aims of this chapter are to review the various aspects/components that are involved in developing aflatoxin-resistant maize germplasm that can lead to breeding commercial resistant lines available to growers. The beginning of the chapter reviewed the initial discoveries of resistant maize lines....

  12. 22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Information To Be Collected on Secondary School Student Host Family Applications F Appendix F to Part 62 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Pt. 62, App. F Appendix F to Part 62—Information To Be Collected on Secondary School Student...

  13. Does selection by resistant hosts trigger local adaptation in plant-pathogen systems?

    PubMed

    Montarry, J; Corbiere, R; Lesueur, S; Glais, I; Andrivon, D

    2006-03-01

    Understanding the consequences of selection by host resistance on pathogen population structure provides useful insights into the dynamics of host-parasite co-evolution processes and is crucial for effective disease management through resistant cultivars. We tested general vs. local population adaptation to host cultivars, by characterizing a French collection of Phytophthora infestans (the causal organism of potato late blight) sampled during two consecutive years on cultivars exhibiting various levels of resistance. Local populations were structured by the host for virulence (qualitative pathogenicity) but also for aggressiveness (quantitative pathogenicity). All populations had a low genotypic diversity for amplified fragment length polymorphisms (AFLPs), and presumably consisted of a few closely related clonal lineages. No correlation was detected between pathogenicity traits and AFLP genotypes. The data support the hypothesis of general adaptation for aggressiveness, to which directional selection for virulence is superimposed when race-specific resistance is introduced. PMID:16599928

  14. Antibiotic-Resistant Infections and Treatment Challenges in the Immunocompromised Host.

    PubMed

    Dumford, Donald M; Skalweit, Marion

    2016-06-01

    This article reviews antibiotic resistance and treatment of bacterial infections in the growing number of patients who are immunocompromised: solid organ transplant recipients, the neutropenic host, and persons with human immunodeficiency virus and AIDS. Specific mechanisms of resistance in both gram-negative and gram-positive bacteria, as well as newer treatment options are addressed elsewhere, and are only briefly discussed in the context of the immunocompromised host. PMID:27208768

  15. Understanding Interactions between Phytopathogenic Phytophthora Effector IpiO and the Host Resistance Protein RB

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Species of phytopathogenic Phytophthora are well known for their ability to cause disease on economically important crops, with almost 100 recognized species targeting close to 300 different hosts. The host resistance protein RB, isolated from wild potato, specifically recognizes the P. infestans Ip...

  16. A susceptible weed host can compromise suppression of Meloidogyne incognita by resistant cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weeds can support nematode reproduction when a non-host or resistant host crop is grown. Meloidogyne incognita, the dominant nematode pathogen of cotton in many areas in the US, reproduces well on prickly sida (Sida spinosa), which is a significant weed in some cotton-producing areas. The developm...

  17. Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

    PubMed Central

    Gjini, Erida; Brito, Patricia H.

    2016-01-01

    Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes. PMID:27078624

  18. Host resistance to visceral leishmaniasis: prevalence and prevention.

    PubMed

    Maran, Naiara; Gomes, Pollyanna Stephanie; Freire-de-Lima, Leonardo; Freitas, Elisangela Oliveira; Freire-de-Lima, Célio Geraldo; Morrot, Alexandre

    2016-04-01

    Visceral leishmaniasis (VL) is a chronic parasitic disease caused by the vector-borne Leishmania donovani and Leishmania (L.) infantum chagasi parasites. The disease affects about 12 million humans in more than 90 countries worldwide. If not treated, the visceral form of Leishmania infection is potentially fatal, yielding about 50000 deaths per year. In the vertebrate host, the Leishmania species causing VL spread systematically to propagate in macrophage reservoirs distributed in the tissues of internal organs, primarily the liver, spleen, bone marrow and the lymph nodes. The infection is associated with evolved mechanisms from the parasite to subvert the host immune system in order to establish a persistent infection. Currently, efforts are being deployed to develop new anti-leishmanial therapies in VL combining immunomodulatory treatment regimens that burst the host immune responses together with leishmanicidal drugs that target the parasite growth. Discoveries in this field are discussed in this article. PMID:26934623

  19. The influence of viral RNA secondary structure on interactions with innate host cell defences

    PubMed Central

    Witteveldt, Jeroen; Blundell, Richard; Maarleveld, Joris J.; McFadden, Nora; Evans, David J.; Simmonds, Peter

    2014-01-01

    RNA viruses infecting vertebrates differ fundamentally in their ability to establish persistent infections with markedly different patterns of transmission, disease mechanisms and evolutionary relationships with their hosts. Although interactions with host innate and adaptive responses are complex and persistence mechanisms likely multi-factorial, we previously observed associations between bioinformatically predicted RNA secondary formation in genomes of positive-stranded RNA viruses with their in vivo fitness and persistence. To analyse this interactions functionally, we transfected fibroblasts with non-replicating, non-translated RNA transcripts from RNA viral genomes with differing degrees of genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts induced interferon-β mediated though RIG-I and PKR activation, the latter associated with rapid induction of antiviral stress granules. A striking inverse correlation was observed between induction of both cellular responses with transcript RNA structure formation that was independent of both nucleotide composition and sequence length. The consistent inability of cells to recognize RNA transcripts possessing GORS extended to downstream differences from unstructured transcripts in expression of TNF-α, other interferon-stimulated genes and induction of apoptosis. This functional association provides novel insights into interactions between virus and host early after infection and provides evidence for a novel mechanism for evading intrinsic and innate immune responses. PMID:24335283

  20. Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in Acinetobacter baumannii

    PubMed Central

    Napier, Brooke A.; Burd, Eileen M.; Satola, Sarah W.; Cagle, Stephanie M.; Ray, Susan M.; McGann, Patrick; Pohl, Jan; Lesho, Emil P.; Weiss, David S.

    2013-01-01

    ABSTRACT The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic. PMID:23695834

  1. Construction of the recombinant broad-host-range plasmids providing their bacterial hosts arsenic resistance and arsenite oxidation ability.

    PubMed

    Drewniak, Lukasz; Ciezkowska, Martyna; Radlinska, Monika; Sklodowska, Aleksandra

    2015-02-20

    The plasmid pSinA of Sinorhizobium sp. M14 was used as a source of functional phenotypic modules, encoding proteins involved in arsenite oxidation and arsenic resistance, to obtain recombinant broad-host-range plasmids providing their bacterial hosts arsenic resistance and arsenite oxidative ability. An arsenite oxidation module was cloned into pBBR1MCS-2 vector yielding plasmid vector pAIO1, while an arsenic resistance module was cloned into pCM62 vector yielding plasmid pARS1. Both plasmid constructs were introduced (separately and together) into the cells of phylogenetically distant (representing Alpha-, Beta-, and Gammaproteobacteria) and physiologically diversified (unable to oxidize arsenite and susceptible/resistant to arsenite and arsenate) bacteria. Functional analysis of the modified strains showed that: (i) the plasmid pARS1 can be used for the construction of strains with an increased resistance to arsenite [up to 20mM of As(III), (ii) the presence of the plasmid pAIO1 in bacteria previously unable to oxidize As(III) to As(V), contributes to the acquisition of arsenite oxidation abilities by these cells, (iii) the highest arsenite utilization rate are observed in the culture of strains harbouring both the plasmids pAIO1 and pARS1, (iv) the strains harbouring the plasmid pAIO1 were able to grow on arsenic-contaminated mine waters (∼ 3.0 mg As L(-1)) without any supplementation. PMID:25617684

  2. Stagonospora nodorum: From pathology to genomics and host resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stagonospora nodorum is a major necrotrophic pathogen of wheat that causes the diseases Stagonospora nodorum leaf and glume blotch. A series of tools and resources, including functional genomics, a genome sequence, proteomics and metabolomics, host-mapping populations, and a worldwide collection of ...

  3. Leaf rust of wheat: Pathogen biology, variation and host resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rusts are important pathogens of angiosperms and gymnosperms. Rust fungi are among the most important pathogens of cereals. Cereal rusts are heteroecious and macrocyclic requiring two taxonomically unrelated hosts to complete a five spore stage life cycle. Cereal rust fungi are highly variable for v...

  4. Predicting the host range of Nystalea ebalea: secondary plant chemistry and host selection by a surrogate biological control agent of Schinus terebinthifolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The safety of weed biological control depends upon the selection and utilization of the target weed by the agent while causing minimal harm to non-target species. Selection of weed species by biological control agents is determined by the presence of behavioral cues, generally host secondary plant c...

  5. Update on Host Plant Resistance Studies of Banded Sunflower Moth and Sunflower Moth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breeding pest-resistance crop cultivars to insects and diseases is one of the primary goals of integrated pest management programs worldwide. Host plant resistance is a tactic that uses the plant's own defenses to reduce injury from pest attack. Among the sunflower (Helianthus annuus L.) insect pest...

  6. The concurrence of Stagonospora nodorum blotch resistance with host-selective toxin insensitivity in tetraploid wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistance to Stagonospora nodorum blotch (SNB) in hexaploid wheat (Triticum aestivum L.) is associated with insensitivity to host-selective toxins (HSTs) produced by the pathogen. In this research, we evaluated the association between HST insensitivity and SNB resistance in tetraploid wheat (T. tur...

  7. Towards Host Plant Resistance against Psyllid Feeding and Transmission of Ca. Liberibacter spp.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of host plant resistance against Ca. Liberibacter spp. will be vital for sustainable global production of citrus, potato, tomato, and other crops, because present control methods are very expensive and chemical-intensive. Resistance to the vector’s feeding and/or the bacterial transmiss...

  8. HOST RESISTANCE TO MURINE MALARIA IN MICE EXPOSED TO THE ADENOSINE TEAMINASE INHIBITOR, 2'-DEOXYCOFORMYCIN

    EPA Science Inventory

    Resistance to infection with the nonlethal rodent malaria parasite Plasmodium yoelii 17XNL is mediated by humoral, T-cell and accessory cell activity. he purpose of this study was to profile host resistance to infection with this organism in mice xposed to 2'-deoxycoformycin (2dC...

  9. Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure

    PubMed Central

    Kubicek-Sutherland, Jessica Z.; Heithoff, Douglas M.; Ersoy, Selvi C.; Shimp, William R.; House, John K.; Marth, Jamey D.; Smith, Jeffrey W.; Mahan, Michael J.

    2015-01-01

    Current antibiotic testing does not include the potential influence of host cell environment on microbial susceptibility and antibiotic resistance, hindering appropriate therapeutic intervention. We devised a strategy to identify the presence of host–pathogen interactions that alter antibiotic efficacy in vivo. Our findings revealed a bacterial mechanism that promotes antibiotic resistance in vivo at concentrations of drug that far exceed dosages determined by standardized antimicrobial testing. This mechanism has escaped prior detection because it is reversible and operates within a subset of host tissues and cells. Bacterial pathogens are thereby protected while their survival promotes the emergence of permanent drug resistance. This host-dependent mechanism of transient antibiotic resistance is applicable to multiple pathogens and has implications for the development of more effective antimicrobial therapies. PMID:26501114

  10. [Repellent and antifeedant effect of secondary metabolites of non-host plants on Plutella xylostella].

    PubMed

    Wei, Hui; Hou, Youming; Yang, Guang; You, Minsheng

    2004-03-01

    Based on the theory of co-evolution between plants and phytophagous insects, the repellent and antifeedant effect of secondary metabolites of non-host plants on diamondback moth(DBM) Plutella xylostella was studied, aimed at finding out the oviposition repellents and antifeedants of insect pests. When the ethanol extracts(Etho Exts) of Bauhinia variegata, Eucalyptus tereticornis, Euphorbia hirta, Duranta repens, Zanthoxylum bungeanum, Magnolia grandiflora, and Nicotiana tabacum were applied respectively, the oviposition repellent rates were all over 80.00%; while after forty-eight hours treatment with the Etho Exts of Euphorbia pulcherrima, Broussonetia papyrifera, Artemisia argyi, Camellia oleifera, Salix babylonica, Euphorbia hirta, Bauhinia variegata, and Setaria viridisa, the antifeedant rates of DBM larvae were all more than 80.00%. PMID:15228000

  11. Evolutionary Paths That Expand Plasmid Host-Range: Implications for Spread of Antibiotic Resistance.

    PubMed

    Loftie-Eaton, Wesley; Yano, Hirokazu; Burleigh, Stephen; Simmons, Ryan S; Hughes, Julie M; Rogers, Linda M; Hunter, Samuel S; Settles, Matthew L; Forney, Larry J; Ponciano, José M; Top, Eva M

    2016-04-01

    The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naïve hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance. PMID:26668183

  12. Characterization of Arabidopsis Transcriptional Responses to Different Aphid Species Reveals Genes that Contribute to Host Susceptibility and Non-host Resistance

    PubMed Central

    Jaouannet, Maëlle; Morris, Jenny A.; Hedley, Peter E.; Bos, Jorunn I. B.

    2015-01-01

    Aphids are economically important pests that display exceptional variation in host range. The determinants of diverse aphid host ranges are not well understood, but it is likely that molecular interactions are involved. With significant progress being made towards understanding host responses upon aphid attack, the mechanisms underlying non-host resistance remain to be elucidated. Here, we investigated and compared Arabidopsis thaliana host and non-host responses to aphids at the transcriptional level using three different aphid species, Myzus persicae, Myzus cerasi and Rhopalosiphum pisum. Gene expression analyses revealed a high level of overlap in the overall gene expression changes during the host and non-host interactions with regards to the sets of genes differentially expressed and the direction of expression changes. Despite this overlap in transcriptional responses across interactions, there was a stronger repression of genes involved in metabolism and oxidative responses specifically during the host interaction with M. persicae. In addition, we identified a set of genes with opposite gene expression patterns during the host versus non-host interactions. Aphid performance assays on Arabidopsis mutants that were selected based on our transcriptome analyses identified novel genes contributing to host susceptibility, host defences during interactions with M. persicae as well to non-host resistance against R. padi. Understanding how plants respond to aphid species that differ in their ability to infest plant species, and identifying the genes and signaling pathways involved, is essential for the development of novel and durable aphid control in crop plants. PMID:25993686

  13. Host mating system and the spread of a disease-resistant allele in a population

    USGS Publications Warehouse

    DeAngelis, D.L.; Koslow, Jennifer M.; Jiang, J.; Ruan, S.

    2008-01-01

    The model presented here modifies a susceptible-infected (SI) host-pathogen model to determine the influence of mating system on the outcome of a host-pathogen interaction. Both deterministic and stochastic (individual-based) versions of the model were used. This model considers the potential consequences of varying mating systems on the rate of spread of both the pathogen and resistance alleles within the population. We assumed that a single allele for disease resistance was sufficient to confer complete resistance in an individual, and that both homozygote and heterozygote resistant individuals had the same mean birth and death rates. When disease invaded a population with only an initial small fraction of resistant genes, inbreeding (selfing) tended to increase the probability that the disease would soon be eliminated from a small population rather than become endemic, while outcrossing greatly increased the probability that the population would become extinct due to the disease.

  14. Host-Based Ribavirin Resistance Influences Hepatitis C Virus Replication and Treatment Response ▿

    PubMed Central

    Ibarra, Kristie D.; Jain, Mamta K.; Pfeiffer, Julie K.

    2011-01-01

    Many individuals infected with hepatitis C virus (HCV) develop a chronic infection, and of those who are treated with pegylated interferon and ribavirin (RBV), many do not respond. While the nucleoside analog RBV improves treatment outcome, and will likely be an important component of therapy with next-generation viral inhibitors, RBV's mechanism is controversial. Most of RBV's proposed mechanisms require RBV import into cells. Therefore, we explored whether host-based RBV resistance develops through reduced cellular uptake, akin to chemotherapy resistance in some cancers. We examined the effect of host-based RBV resistance on HCV replication in cultured hepatoma Huh7.5 liver cells and whether RBV resistance develops in HCV patients. When Huh7.5 cells were exposed to RBV, resistance developed through reduced RBV uptake via the ENT1 nucleoside transporter and antiviral efficacy was reduced. The uptake defect in RBV-resistant cells was specific to RBV, since transport of another ENT1 substrate, cytidine, was unaffected. Importantly, RBV uptake significantly declined in HCV patient peripheral blood mononuclear cells (PBMCs) following 4 weeks of therapy. Furthermore, maintenance of RBV uptake correlated with rapid treatment response. Our results uncovered a novel form of antiviral drug resistance and suggest that host-based RBV resistance develops in HCV patients undergoing therapy and that maintenance of RBV uptake may contribute to rapid viral clearance. PMID:21543469

  15. Host genotype by parasite genotype interactions underlying the resistance of anopheline mosquitoes to Plasmodium falciparum

    PubMed Central

    Lambrechts, Louis; Halbert, Jean; Durand, Patrick; Gouagna, Louis C; Koella, Jacob C

    2005-01-01

    Background Most studies on the resistance of mosquitoes to their malaria parasites focus on the response of a mosquito line or colony against a single parasite genotype. In natural situations, however, it may be expected that mosquito-malaria relationships are based, as are many other host-parasite systems, on host genotype by parasite genotype interactions. In such systems, certain hosts are resistant to one subset of the parasite's genotypes, while other hosts are resistant to a different subset. Methods To test for genotype by genotype interactions between malaria parasites and their anopheline vectors, different genetic backgrounds (families consisting of the F1 offspring of individual females) of the major African vector Anopheles gambiae were challenged with several isolates of the human malaria parasite Plasmodium falciparum (obtained from naturally infected children in Kenya). Results Averaged across all parasites, the proportion of infected mosquitoes and the number of oocysts found in their midguts were similar in all mosquito families. Both indices of resistance, however, differed considerably among isolates of the parasite. In particular, no mosquito family was most resistant to all parasites, and no parasite isolate was most infectious to all mosquitoes. Conclusions These results suggest that the level of mosquito resistance depends on the interaction between its own and the parasite's genotype. This finding thus emphasizes the need to take into account the range of genetic diversity exhibited by mosquito and malaria field populations in ideas and studies concerning the control of malaria. PMID:15644136

  16. Antioxidant Secondary Metabolites in Cereals: Potential Involvement in Resistance to Fusarium and Mycotoxin Accumulation.

    PubMed

    Atanasova-Penichon, Vessela; Barreau, Christian; Richard-Forget, Florence

    2016-01-01

    Gibberella and Fusarium Ear Rot and Fusarium Head Blight are major diseases affecting European cereals. These diseases are mainly caused by fungi of the Fusarium genus, primarily Fusarium graminearum and Fusarium verticillioides. These Fusarium species pose a serious threat to food safety because of their ability to produce a wide range of mycotoxins, including type B trichothecenes and fumonisins. Many factors such as environmental, agronomic or genetic ones may contribute to high levels of accumulation of mycotoxins in the grain and there is an urgent need to implement efficient and sustainable management strategies to reduce mycotoxin contamination. Actually, fungicides are not fully efficient to control the mycotoxin risk. In addition, because of harmful effects on human health and environment, their use should be seriously restricted in the near future. To durably solve the problem of mycotoxin accumulation, the breeding of tolerant genotypes is one of the most promising strategies for cereals. A deeper understanding of the molecular mechanisms of plant resistance to both Fusarium and mycotoxin contamination will shed light on plant-pathogen interactions and provide relevant information for improving breeding programs. Resistance to Fusarium depends on the plant ability in preventing initial infection and containing the development of the toxigenic fungi while resistance to mycotoxin contamination is also related to the capacity of plant tissues in reducing mycotoxin accumulation. This capacity can result from two mechanisms: metabolic transformation of the toxin into less toxic compounds and inhibition of toxin biosynthesis. This last mechanism involves host metabolites able to interfere with mycotoxin biosynthesis. This review aims at gathering the latest scientific advances that support the contribution of grain antioxidant secondary metabolites to the mechanisms of plant resistance to Fusarium and mycotoxin accumulation. PMID:27148243

  17. Antioxidant Secondary Metabolites in Cereals: Potential Involvement in Resistance to Fusarium and Mycotoxin Accumulation

    PubMed Central

    Atanasova-Penichon, Vessela; Barreau, Christian; Richard-Forget, Florence

    2016-01-01

    Gibberella and Fusarium Ear Rot and Fusarium Head Blight are major diseases affecting European cereals. These diseases are mainly caused by fungi of the Fusarium genus, primarily Fusarium graminearum and Fusarium verticillioides. These Fusarium species pose a serious threat to food safety because of their ability to produce a wide range of mycotoxins, including type B trichothecenes and fumonisins. Many factors such as environmental, agronomic or genetic ones may contribute to high levels of accumulation of mycotoxins in the grain and there is an urgent need to implement efficient and sustainable management strategies to reduce mycotoxin contamination. Actually, fungicides are not fully efficient to control the mycotoxin risk. In addition, because of harmful effects on human health and environment, their use should be seriously restricted in the near future. To durably solve the problem of mycotoxin accumulation, the breeding of tolerant genotypes is one of the most promising strategies for cereals. A deeper understanding of the molecular mechanisms of plant resistance to both Fusarium and mycotoxin contamination will shed light on plant-pathogen interactions and provide relevant information for improving breeding programs. Resistance to Fusarium depends on the plant ability in preventing initial infection and containing the development of the toxigenic fungi while resistance to mycotoxin contamination is also related to the capacity of plant tissues in reducing mycotoxin accumulation. This capacity can result from two mechanisms: metabolic transformation of the toxin into less toxic compounds and inhibition of toxin biosynthesis. This last mechanism involves host metabolites able to interfere with mycotoxin biosynthesis. This review aims at gathering the latest scientific advances that support the contribution of grain antioxidant secondary metabolites to the mechanisms of plant resistance to Fusarium and mycotoxin accumulation. PMID:27148243

  18. Differential display analysis of hemocytes from schistosome-resistant and schistosome-susceptible intermediate hosts.

    PubMed

    Schneider, O; Zelck, U E

    2001-06-01

    Hemocytes from schistosome-resistant and schistosome-susceptible Biomphalaria glabrata differ fundamentally in their behavior towards an invading parasite. When the schistosome infects a resistant snail host it is quickly surrounded by hemocytes, encapsulated and destroyed. Hemocytes from susceptible hosts fail to kill the parasite. To detect the differences between these two host phenotypes, we used differential-display reverse-transcription PCR (DDRT-PCR), based on RNA extracted from isolated hemocytes. A number of differentially expressed fragments from resistant and susceptible snails were detected by DDRT-PCR and confirmed using single-strand conformation polymorphism. These methods proved to be sensitive enough to allow comparison and verification of differential gene expression in our system, where only small numbers of cells are available. The most interesting phenotype-specific fragments detected so far show sequence homologies to an adhesion molecule, defensin, serine/ threonine kinases, peroxidases and glycosidases. PMID:11411951

  19. Induced Bacterial Cross-Resistance toward Host Antimicrobial Peptides: A Worrying Phenomenon

    PubMed Central

    Fleitas, Osmel; Franco, Octávio L.

    2016-01-01

    Bacterial resistance to conventional antibiotics has reached alarming levels, threatening to return to the pre-antibiotic era. Therefore, the search for new antimicrobial compounds that overcome the resistance phenomenon has become a priority. Antimicrobial peptides (AMPs) appear as one of the most promising antibiotic medicines. However, in recent years several AMP-resistance mechanisms have been described. Moreover, the AMP-resistance phenomenon has become more complex due to its association with cross-resistance toward AMP effectors of the host innate immune system. In this context, the use of AMPs as a therapeutic option could be potentially hazardous, since bacteria could develop resistance toward our innate immune system. Here, we review the findings of major studies that deal with the AMP cross-resistance phenomenon. PMID:27047486

  20. Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.

    PubMed

    Bushman, Mary; Morton, Lindsay; Duah, Nancy; Quashie, Neils; Abuaku, Benjamin; Koram, Kwadwo A; Dimbu, Pedro Rafael; Plucinski, Mateusz; Gutman, Julie; Lyaruu, Peter; Kachur, S Patrick; de Roode, Jacobus C; Udhayakumar, Venkatachalam

    2016-03-16

    Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures. PMID:26984625

  1. Influence of host resistance on viral adaptation: hepatitis C virus as a case study

    PubMed Central

    Plauzolles, Anne; Lucas, Michaela; Gaudieri, Silvana

    2015-01-01

    Genetic and cellular studies have shown that the host’s innate and adaptive immune responses are an important correlate of viral infection outcome. The features of the host’s immune response (host resistance) reflect the coevolution between hosts and pathogens that has occurred over millennia, and that has also resulted in a number of strategies developed by viruses to improve fitness and survival within the host (viral adaptation). In this review, we discuss viral adaptation to host immune pressure via protein–protein interactions and sequence-specific mutations. Specifically, we will present the “state of play” on viral escape mutations to host T-cell responses in the context of the hepatitis C virus, and their influence on infection outcome. PMID:25897250

  2. Parasitic plants of the genus Cuscuta and their interaction with susceptible and resistant host plants

    PubMed Central

    Kaiser, Bettina; Vogg, Gerd; Fürst, Ursula B.; Albert, Markus

    2015-01-01

    By comparison with plant–microbe interaction, little is known about the interaction of parasitic plants with their hosts. Plants of the genus Cuscuta belong to the family of Cuscutaceae and comprise about 200 species, all of which live as stem holoparasites on other plants. Cuscuta spp. possess no roots nor fully expanded leaves and the vegetative portion appears to be a stem only. The parasite winds around plants and penetrates the host stems via haustoria, forming direct connections to the vascular bundles of their hosts to withdraw water, carbohydrates, and other solutes. Besides susceptible hosts, a few plants exist that exhibit an active resistance against infestation by Cuscuta spp. For example, cultivated tomato (Solanum lycopersicum) fends off Cuscuta reflexa by means of a hypersensitive-type response occurring in the early penetration phase. This report on the plant–plant dialog between Cuscuta spp. and its host plants focuses on the incompatible interaction of C. reflexa with tomato. PMID:25699071

  3. Inbreeding alters resistance to insect herbivory and host plant quality in Mimulus guttatus (Scrophulariaceae).

    PubMed

    Carr, David E; Eubanks, Micky D

    2002-01-01

    Previous studies have demonstrated genetic variation for resistance to insect herbivores and host plant quality. The effect of plant mating system, an important determinant of the distribution of genetic variation, on host plant characteristics has received almost no attention. This study used a controlled greenhouse experiment to examine the effect of self- and cross-pollination in Mimulus guttatus (Scrophulariaceae) on resistance to and host plant quality for the xylem-feeding spittlebug Philaenus spumarius (Homoptera: Cercopidae). Spittlebugs were found to have a negative effect on two important fitness components in M. guttatus, flower production and above ground biomass. One of two M. guttatus populations examined showed a significant interaction between the pollination and herbivore treatments. In this case, the detrimental effects of herbivores on biomass and flower production were much more pronounced in inbred (self) plants. The presence of spittlebug nymphs increased inbreeding depression by as much as three times. Pollination treatments also had significant effects on important components of herbivore fitness, but these effects were in opposite directions in our two host plant populations. Spittlebug nymphs maturing on self plants emerged as significantly larger adults in one of our host plant populations, indicating that inbreeding increased host plant quality. In our second host plant population, spittlebug nymphs took significantly longer to develop to adulthood on self plants, indicating that inbreeding decreased host plant quality. Taken together these results suggest that the degree of inbreeding in host plant populations can have important and perhaps complex effects on the dynamics of plant-herbivore interactions and on mating-system evolution in the host. PMID:11913665

  4. Host resistance in cattle to infestation with the cattle tick Rhipicephalus microplus.

    PubMed

    Jonsson, N N; Piper, E K; Constantinoiu, C C

    2014-11-01

    Resistance to Rhipicephalus microplus infestation in cattle has many effector mechanisms, each of which is likely to be modulated by complex, interacting factors. Some of the mechanisms of host resistance and their modulating factors have been identified and quantified, although much remains to be explained. The variation in resistance to tick infestation is most marked between Bos taurus and Bos indicus cattle, taurine cattle given the same exposure carrying between five and 10 times as many ticks as indicine cattle. Tick resistance is mostly manifest against attaching larvae, which attempt to feed often and without success, death occurring mostly within 24 h of finding a host. There is evidence of innate and adaptive immune response to tick infestation, and it appears that the relative importance of each differs between indicine and taurine cattle. There is conflicting information regarding the role of humoral immunity in tick resistance, and recent studies indicate that strong IgG responses to tick antigens are not protective. A strong T-cell-mediated response directed against larval stages, as mounted by indicine cattle, seems to be protective. Variation in the extracellular matrix of skin (epidermal growth factors, collagens and other matrix components such as lumican) also contributes to variation in host resistance. PMID:25313455

  5. CHEMOTHERAPY, WITHIN-HOST ECOLOGY AND THE FITNESS OF DRUG-RESISTANT MALARIA PARASITES

    PubMed Central

    Huijben, Silvie; Nelson, William A.; Wargo, Andrew R.; Sim, Derek G.; Drew, Damien R.; Read, Andrew F.

    2011-01-01

    A major determinant of the rate at which drug-resistant malaria parasites spread through a population is the ecology of resistant and sensitive parasites sharing the same host. Drug treatment can significantly alter this ecology by removing the drug-sensitive parasites, leading to competitive release of resistant parasites. Here, we test the hypothesis that the spread of resistance can be slowed by reducing drug treatment and hence restricting competitive release. Using the rodent malaria model Plasmodium chabaudi, we found that low-dose chemotherapy did reduce competitive release. A higher drug dose regimen exerted stronger positive selection on resistant parasites for no detectable clinical gain. We estimated instantaneous selection coefficients throughout the course of replicate infections to analyze the temporal pattern of the strength and direction of within-host selection. The strength of selection on resistance varied through the course of infections, even in untreated infections, but increased immediately following drug treatment, particularly in the high-dose groups. Resistance remained under positive selection for much longer than expected from the half life of the drug. Although there are many differences between mice and people, our data do raise the question whether the aggressive treatment regimens aimed at complete parasite clearance are the best resistance-management strategies for humans. PMID:20584075

  6. Quantitative phenotyping of powdery mildew resistance in grapevine reveals differences in host resistance biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recent demonstration of race-specific resistance to Erysiphe necator has encouraged grapevine breeders to identify and introgress quantitative resistance genes exhibiting complementary mechanisms. In 2012, we established a phenotyping center (VitisGenPM) for detailed evaluation of resistance to...

  7. Evaluations of melon germplasm reported to exhibit host plant resistance to sweetpotato whitefly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sweetpotato whitefly (MEAM1 cryptic species of Bemisia tabaci; SPWF) displaced B. tabaci biotype A in 1991 in the lower desert area of southern California and the adjoining areas of Arizona and western Mexico. The search for high-level host plant resistance to this devastating insect has been ongoin...

  8. Host plant resistance in melon (Cucumis melo L.) to sweetpotato whitefly in California and Arizona

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sweetpotato whitefly (MEAM1 cryptic species of Bemisia tabaci; SPWF) feeding severely impacts fall season melon yield and quality in the lower deserts of California and Arizona. Melon accessions PI 313970 and TGR 1551 (PI 482420) have been reported to exhibit host plant resistance (HPR) to SPWF. Pot...

  9. Fecal Microbiota Transplantation Inhibits Multidrug-Resistant Gut Pathogens: Preliminary Report Performed in an Immunocompromised Host.

    PubMed

    Biliński, Jarosław; Grzesiowski, Paweł; Muszyński, Jacek; Wróblewska, Marta; Mądry, Krzysztof; Robak, Katarzyna; Dzieciątkowski, Tomasz; Wiktor-Jedrzejczak, Wiesław; Basak, Grzegorz W

    2016-06-01

    Colonization of the gastrointestinal tract with multidrug-resistant (MDR) bacteria is a consequence of gut dysbiosis. We describe the successful utilization of fecal microbiota transplantation to inhibit Klebsiella pneumoniae MBL(+) and Escherichia coli ESBL(+) gut colonization in the immunocompromised host as a novel tool in the battle against MDR microorganisms. ClinicalTrials.gov identifier NCT02461199. PMID:26960790

  10. Combining Reflective Mulch and Host Plant Resistance for Sweetpotato Whitefly (Hemiptera: Aleyrodidae) Management in Watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to evaluate the use of reflective mulch and host plant resistance for the management of the B-biotype sweetpotato whitefly, Bemisia tabaci (Gennadius), in watermelon [Citrullus lanatus var. lanatus (Thunberg) Matsum & Nakai]. Whitefly abundance data were collected under both g...

  11. Health trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome

    PubMed Central

    Lough, Graham; Kyriazakis, Ilias; Bergmann, Silke; Lengeling, Andreas; Doeschl-Wilson, Andrea B.

    2015-01-01

    Resistance and tolerance are two alternative strategies hosts can adopt to survive infections. Both strategies may be genetically controlled. To date, the relative contribution of resistance and tolerance to infection outcome is poorly understood. Here, we use a bioluminescent Listeria monocytogenes (Lm) infection challenge model to study the genetic determination and dynamic contributions of host resistance and tolerance to listeriosis in four genetically diverse mouse strains. Using conventional statistical analyses, we detect significant genetic variation in both resistance and tolerance, but cannot capture the time-dependent relative importance of either host strategy. We overcome these limitations through the development of novel statistical tools to analyse individual infection trajectories portraying simultaneous changes in infection severity and health. Based on these tools, early expression of resistance followed by expression of tolerance emerge as important hallmarks for surviving Lm infections. Our trajectory analysis further reveals that survivors and non-survivors follow distinct infection paths (which are also genetically determined) and provides new survival thresholds as objective endpoints in infection experiments. Future studies may use trajectories as novel traits for mapping and identifying genes that control infection dynamics and outcome. A Matlab script for user-friendly trajectory analysis is provided. PMID:26582028

  12. Increased survival of experimentally evolved antimicrobial peptide-resistant Staphylococcus aureus in an animal host

    PubMed Central

    Dobson, Adam J; Purves, Joanne; Rolff, Jens

    2014-01-01

    Antimicrobial peptides (AMPs) have been proposed as new class of antimicrobial drugs, following the increasing prevalence of bacteria resistant to antibiotics. Synthetic AMPs are functional analogues of highly evolutionarily conserved immune effectors in animals and plants, produced in response to microbial infection. Therefore, the proposed therapeutic use of AMPs bears the risk of ‘arming the enemy’: bacteria that evolve resistance to AMPs may be cross-resistant to immune effectors (AMPs) in their hosts. We used a panel of populations of Staphylococcus aureus that were experimentally selected for resistance to a suite of individual AMPs and antibiotics to investigate the ‘arming the enemy’ hypothesis. We tested whether the selected strains showed higher survival in an insect model (Tenebrio molitor) and cross-resistance against other antimicrobials in vitro. A population selected for resistance to the antimicrobial peptide iseganan showed increased in vivo survival, but was not more virulent. We suggest that increased survival of AMP-resistant bacteria almost certainly poses problems to immune-compromised hosts. PMID:25469169

  13. Early stage phytohormone and fatty acid profiles of plants associated with host and non-host resistance to hessian fly (Diptera: Cecidomyiidae) infestation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytohormones and fatty acids play important roles in plant resistance to insects and pathogens. In this study, we investigated the similarities and differences in the accumulations of phytohormones and fatty acids in the resistant wheat (Triticum aestivum L.) ‘Molly’ and the non-host rice (Oryza sa...

  14. Parasite diversity drives rapid host dynamics and evolution of resistance in a bacteria‐phage system

    PubMed Central

    Betts, Alex; Gifford, Danna R.; MacLean, R. Craig; King, Kayla C.

    2016-01-01

    Host–parasite evolutionary interactions are typically considered in a pairwise species framework. However, natural infections frequently involve multiple parasites. Altering parasite diversity alters ecological and evolutionary dynamics as parasites compete and hosts resist multiple infection. We investigated the effects of parasite diversity on host–parasite population dynamics and evolution using the pathogen Pseudomonas aeruginosa and five lytic bacteriophage parasites. To manipulate parasite diversity, bacterial populations were exposed for 24 hours to either phage monocultures or diverse communities containing up to five phages. Phage communities suppressed host populations more rapidly but also showed reduced phage density, likely due to interphage competition. The evolution of resistance allowed rapid bacterial recovery that was greater in magnitude with increases in phage diversity. We observed no difference in the extent of resistance with increased parasite diversity, but there was a profound impact on the specificity of resistance; specialized resistance evolved to monocultures through mutations in a diverse set of genes. In summary, we demonstrate that parasite diversity has rapid effects on host–parasite population dynamics and evolution by selecting for different resistance mutations and affecting the magnitude of bacterial suppression and recovery. Finally, we discuss the implications of phage diversity for their use as biological control agents. PMID:27005577

  15. Use of a secondary host by non-outbreak populations of the gypsy moth. [Pinus rigida; Quercus spp; Lymantria dispar

    SciTech Connect

    Rossiter, M.

    1987-08-01

    Oaks are the favored host of gypsy moths in the northeastern US, although the herbivore expands its host range dramatically during an outbreak. Pitch pine, a secondary host because of its unacceptability for early development, was found to be frequently used for oviposition in oak-pitch pine forests with non-outbreak populations. This observation led to the study of ecological and behavioral factors that can contribute to the use of a secondary host under low-density conditions by an irruptive herbivore species. A series of manipulative field and laboratory experiments plus a study of natural history provided data on the pattern of pitch pine use during the life cycle of the gypsy moth, the effect of pitch pine on larval growth, and the differential impact of natural enemies depending on host use. It was found that: 1) egg masses occurred far more frequently on pitch pine than was expected based on the frequency of pitch pine in forests with low-density gypsy moth populations; 2) in the laboratory, early-instar larvae could not survive on pitch pine while late-instar larvae grew well; 3) in the field, larvae began to use pitch pine to feed and rest after the onset of the fourth instar. Compared to oak, 4) egg masses on pitch pine experienced less parasitism; 5) the microhabitat of pitch pine held less nuclear polyhedrosis virus (NPV), a major mortality agent of the gypsy moth; 6) individuals hatching from eggs laid on pitch pine were less infected with NPV; and 7) larvae dosed with a known amount of NPV survived longer when feeding on pitch pine foliage. The use of pitch pine by individuals in low-density gypsy moth populations appeared to be beneficial and may have an important effect on population dynamics. The mobility associated with host switching by late-instar larvae and with dispersal by first-instar larvae oviposited on unacceptable food may represent an important mechanism for host-range extension.

  16. Roles of EDR1 in non-host resistance of Arabidopsis.

    PubMed

    Hiruma, Kei; Takano, Yoshitaka

    2011-11-01

    Entry control of Arabidopsis thaliana against non-adapted powdery mildews largely depends on the PEN1 secretion pathway and the PEN2-PEN3 antifungal metabolite pathway, and is critical for non-host resistance. In a recent study, we reported that ENHANCED DISEASE RESISTANCE 1 (EDR1) plays a role in entry control against a non-adapted anthracnose fungus, which exhibits an infection style distinct from that of powdery mildews. Results obtained using edr1 pen2 double mutants indicate that the contribution of EDR1 to non-host resistance is independent of that of the PEN2-mediated defence pathway. Comparative transcript profiling revealed that EDR1 is critical for expression of four plant defensin genes. The MYC2-encoded transcription factor represses defensin expression. Inactivation of MYC fully restored defensin expression in edr1 mutants, implying that EDR1 cancels MYC2 function to regulate defensin expression. These findings indicate that EDR1 exerts a critical role in non-host resistance, in part by inducing antifungal peptide expression via interference in MYC2-mediated repressor function. PMID:22057322

  17. BMP7 Expression Correlates with Secondary Drug Resistance in Mantle Cell Lymphoma

    PubMed Central

    Roux, Sébastien; Lamy, Thierry; Bosq, Jacques; Bernard, Marc; Fest, Thierry; Lazar, Vladimir; Lenoir, Gilbert; Ribrag, Vincent

    2013-01-01

    Purpose We designed a gene profiling experiment to identify genes involved in secondary drug resistance in mantle cell lymphomas (MCL). Experimental Design We obtained paired tissue samples collected from the same patients before treatment and after relapse or progression. Variations in gene expression between the 2 samples were estimated for 5 patients. For each gene, the mean variation was estimated for patients with a refractory primary tumor and for responders who developed secondary drug resistance. Nine genes of interest were selected on the basis of the magnitude and statistical significance of the variation of expression in responders and non-responders. Results BMP7 was the only one with significantly increased expression at relapse in patients who developed secondary resistance. Validation of BMP7 as a key gene involved in secondary resistance was performed using cultures of cell line. Incubation of BMP7 with MCL cell lines increased their resistance to bortezomib and cytarabine, while inhibition of BMP7 expression by siRNA correlated with increased cell death linked to drug application. Conclusion Variations in gene expression after treatment point out BMP7 as a key gene involved in secondary resistance in mantle cell lymphoma. PMID:24069261

  18. Probable Levofloxacin-associated Secondary Intracranial Hypertension in a Child With Multidrug-resistant Tuberculosis.

    PubMed

    van der Laan, Louvina E; Schaaf, H Simon; Solomons, Regan; Willemse, Marianne; Mohamed, Nabil; Baboolal, Sandika O; Hesseling, Anneke C; van Toorn, Ronald; Garcia-Prats, Anthony J

    2016-06-01

    Fluoroquinolones are a key component of multidrug-resistant tuberculosis treatment. We describe the first reported case of probable levofloxacin-associated intracranial hypertension in a 6-year-old girl with pulmonary multidrug-resistant tuberculosis. The case highlights the potential risk of secondary intracranial hypertension in multidrug-resistant tuberculosis patients who require prolonged fluoroquinolone therapy and the need for ophthalmologic screening in children with suggestive signs and symptoms. PMID:26974890

  19. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics.

    PubMed

    Nakahara, Koichiro; Wakasa-Morimoto, Chiaki; Kobayashi, Masanori; Miki, Shigeru; Noshi, Takeshi; Seki, Takahiro; Kanamori-Koyama, Mikiko; Kawauchi, Shinobu; Suyama, Akemi; Fujishita, Toshio; Yoshinaga, Tomokazu; Garvey, Edward P; Johns, Brian A; Foster, Scott A; Underwood, Mark R; Sato, Akihiko; Fujiwara, Tamio

    2009-02-01

    Passage of HIV-1 in the presence of integrase inhibitors (INIs) generates resistant viruses that have mutations in the integrase region. Integrase-resistant mutations Q148K and Q148R were identified as primary mutations with the passage of HIV-1 IIIB in the presence of INIs S-1360 or S/GSK-364735, respectively. Secondary amino acid substitutions E138K or G140S were observed when passage with INI was continued. The role of these mutations was investigated with molecular clones. Relative to Q148K alone, Q148K/E138K had 2- and >6-fold increases in resistance to S-1360 and S/GSK-364735, respectively, and the double mutant had slightly better infectivity and replication kinetics. In contrast, Q148K/G140S and Q148R/E138K had nearly equivalent or slightly reduced fold resistance to the INI compared with their respective Q148 primary mutants, and had increases in infectivity and replication kinetics. Recovery of these surrogates of viral fitness coincided with the recovery of integration efficiency of viral DNA into the host cell chromosome for these double mutants. These data show that recovery of viral integration efficiency can be an important factor for the emergence and maintenance of INI-resistant mutations. PMID:19027039

  20. Codivergence of the primary bacterial endosymbiont of psyllids versus host switches and replacement of their secondary bacterial endosymbionts.

    PubMed

    Hall, Aidan A G; Morrow, Jennifer L; Fromont, Caroline; Steinbauer, Martin J; Taylor, Gary S; Johnson, Scott N; Cook, James M; Riegler, Markus

    2016-09-01

    Coevolution between insects and bacterial endosymbionts contributes to the success of many insect lineages. For the first time, we tested for phylogenetic codivergence across multiple taxonomic scales, from within genera to superfamily between 36 psyllid species of seven recognised families (Hemiptera: Psylloidea), their exclusive primary endosymbiont Carsonella and more diverse secondary endosymbionts (S-endosymbionts). Within Aphalaridae, we found that Carsonella and S-endosymbionts were fixed in one Glycaspis and 12 Cardiaspina populations. The dominant S-endosymbiont was Arsenophonus, while Sodalis was detected in one Cardiaspina species. We demonstrated vertical transmission for Carsonella and Arsenophonus in three Cardiaspina species. We found strong support for strict cospeciation and validated the informative content of Carsonella as extended host genome for inference of psyllid relationships. However, S-endosymbiont and host phylogenies were incongruent, and displayed signs of host switching and endosymbiont replacement. The high incidence of Arsenophonus in psyllids and other plant sap-feeding Hemiptera may be due to repeated host switching within this group. In two psyllid lineages, Arsenophonus and Sodalis genes exhibited accelerated evolutionary rates and AT-biases characteristic of long-term host associations. Together with strict vertical transmission and 100% prevalence within host populations, our results suggest an obligate, and not facultative, symbiosis between psyllids and some S-endosymbionts. PMID:27114069

  1. Distinct host cell proteins incorporated by SIV replicating in CD4+ T Cells from natural disease resistant versus non-natural disease susceptible hosts

    PubMed Central

    2010-01-01

    Background Enveloped viruses including the simian immunodeficiency virus (SIV) replicating within host cells acquire host proteins upon egress from the host cells. A number of studies have catalogued such host proteins, and a few have documented the potential positive and negative biological functions of such host proteins. The studies conducted herein utilized proteomic analysis to identify differences in the spectrum of host proteins acquired by a single source of SIV replicating within CD4+ T cells from disease resistant sooty mangabeys and disease susceptible rhesus macaques. Results While a total of 202 host derived proteins were present in viral preparations from CD4+ T cells from both species, there were 4 host-derived proteins that consistently and uniquely associated with SIV replicating within CD4+ T cells from rhesus macaques but not sooty mangabeys; and, similarly, 28 host-derived proteins that uniquely associated with SIV replicating within CD4+ T cells from sooty mangabeys, but not rhesus macaques. Of interest was the finding that of the 4 proteins uniquely present in SIV preparations from rhesus macaques was a 26 S protease subunit 7 (MSS1) that was shown to enhance HIV-1 'tat" mediated transactivation. Among the 28 proteins found in SIV preparations from sooty mangabeys included several molecules associated with immune function such as CD2, CD3ε, TLR4, TLR9 and TNFR and a bioactive form of IL-13. Conclusions The finding of 4 host proteins that are uniquely associated with SIV replicating within CD4+ T cells from disease susceptible rhesus macaques and 28 host proteins that are uniquely associated with SIV replicating within CD4+ T cells from disease resistant sooty mangabeys provide the foundation for determining the potential role of each of these unique host-derived proteins in contributing to the polarized clinical outcome in these 2 species of nonhuman primates. PMID:21162735

  2. Mannose-Binding Lectin Regulates Host Resistance and Pathology during Experimental Infection with Trypanosoma cruzi

    PubMed Central

    Rothfuchs, Antonio Gigliotti; Roffê, Ester; Gibson, Amanda; Cheever, Allen W.; Ezekowitz, R. Alan B.; Takahashi, Kazue; Steindel, Mario; Sher, Alan; Báfica, André

    2012-01-01

    Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas’ disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas’ disease. In this study we employed MBL−/− mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas’ disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL−/− mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL−/− mice. Importantly, MBL−/− mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen. PMID:23139754

  3. Mannose-binding lectin regulates host resistance and pathology during experimental infection with Trypanosoma cruzi.

    PubMed

    Rothfuchs, Antonio Gigliotti; Roffê, Ester; Gibson, Amanda; Cheever, Allen W; Ezekowitz, R Alan B; Takahashi, Kazue; Steindel, Mario; Sher, Alan; Báfica, André

    2012-01-01

    Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas' disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. In this study we employed MBL(-/-) mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas' disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL(-/-) mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL(-/-) mice. Importantly, MBL(-/-) mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen. PMID:23139754

  4. New tricks for old dogs: countering antibiotic resistance in tuberculosis with host-directed therapeutics

    PubMed Central

    Hawn, Thomas R.; Shah, Javeed A.; Kalman, Daniel

    2015-01-01

    Summary Despite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis (TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co-infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here we discuss recent progress in so called ‘host-directed therapeutics’ (HDTs), focusing on two general mechanistic strategies: (i) HDTs that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDTs that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDTs hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic-resistant strains, and may have activity against non-replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDTs to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDTs as effective adjunctive treatment options for TB. PMID:25703571

  5. Secondary mutations as mediators of resistance to targeted therapy in leukemia

    PubMed Central

    Cortes, Jorge; Ravandi, Farhad; Patel, Keyur P.; Burger, Jan A.; Konopleva, Marina; Kantarjian, Hagop

    2015-01-01

    The advent of small molecule-based targeted therapy has improved the treatment of both acute and chronic leukemias. Resistance to small molecule inhibitors has emerged as a common theme. The most frequent mode of acquired resistance is the acquisition of point mutations in the kinase domain. FLT3 inhibitors have improved response rates in FLT3-mutated acute myeloid leukemia (AML). The occurrence of the ATP-binding site and activation loop mutations confers varying degrees of resistance to the individual FLT3 inhibitors. Second-generation FLT3 inhibitors such as crenolanib may overcome the resistance of these mutations. Furthermore, nonmutational mechanisms of resistance such as prosurvival pathways and bone marrow signaling may be upregulated in FLT3 inhibitor-resistant AML with secondary kinase domain mutations. More recently, point mutations conferring resistance to the Bruton tyrosine kinase inhibitor ibrutinib in chronic lymphocytic leukemia, arsenic trioxide in acute promyelocytic leukemia, and the BH3-mimetic ABT199 in lymphoma have been identified. In chronic myeloid leukemia, the emergence of tyrosine kinase domain mutations has historically been the dominant mechanism of resistance. The early identification of secondary point mutations and their downstream effects along with the development of second- or third-generation inhibitors and rationally designed small molecule combinations are potential strategies to overcome mutation-mediated resistance. PMID:25795921

  6. Extracellular matrix-associated proteome changes during non-host resistance in citrus-Xanthomonas interactions.

    PubMed

    Swaroopa Rani, Tirupaati; Podile, Appa Rao

    2014-04-01

    Non-host resistance (NHR) is a most durable broad-spectrum resistance employed by the plants to restrict majority of pathogens. Plant extracellular matrix (ECM) is a critical defense barrier. Understanding ECM responses during interaction with non-host pathogen will provide insights into molecular events of NHR. In this study, the ECM-associated proteome was compared during interaction of citrus with pathogen Xanthomonas axonopodis pv. citri (Xac) and non-host pathogen Xanthomonas oryzae pv. oryzae (Xoo) at 8, 16, 24 and 48 h post inoculation. Comprehensive analysis of ECM-associated proteins was performed by extracting wall-bound and soluble ECM components using both destructive and non-destructive procedures. A total of 53 proteins was differentially expressed in citrus-Xanthomonas host and non-host interaction, out of which 44 were identified by mass spectrometry. The differentially expressed proteins were related to (1) defense-response (5 pathogenesis-related proteins, 3 miraculin-like proteins (MIR, MIR1 and MIR2) and 2 proteases); (2) enzymes of reactive oxygen species (ROS) metabolism [Cu/Zn superoxide dismutase (SOD), Fe-SOD, ascorbate peroxidase and 2-cysteine-peroxiredoxin]; (3) signaling (lectin, curculin-like lectin and concanavalin A-like lectin kinase); and (4) cell-wall modification (α-xylosidase, glucan 1, 3 β-glucosidase, xyloglucan endotransglucosylase/hydrolase). The decrease in ascorbate peroxidase and cysteine-peroxiredoxin could be involved in maintenance of ROS levels. Increase in defense, cell-wall remodeling and signaling proteins in citrus-Xoo interaction suggests an active involvement of ECM in execution of NHR. Partially compromised NHR in citrus against Xoo, upon Brefeldin A pre-treatment supported the role of non-classical secretory proteins in this phenomenon. PMID:24117905

  7. Heterogeneous Mechanisms of Secondary Resistance and Clonal Selection in Sarcoma during Treatment with Nutlin

    PubMed Central

    Laroche, Audrey; Tran-Cong, Kevin; Chaire, Vanessa; Lagarde, Pauline; Hostein, Isabelle; Coindre, Jean-Michel; Chibon, Frederic; Neuville, Agnes; Lesluyes, Tom; Lucchesi, Carlo; Italiano, Antoine

    2015-01-01

    Nutlin inhibits TP53-MDM2 interaction and is under investigation in soft-tissue sarcomas (STS) and other malignancies. Molecular mechanisms of secondary resistance to nutlin in STS are unknown. We performed whole-transcriptome sequencing (RNA-seq) on three pretreatment and secondary resistant STS cell lines selected based on their high primary sensitivity to nutlin. Our data identified a subset of cancer gene mutations and ploidy variations that were positively selected following treatment, including TP53 mutations in 2 out of 3 resistant cell lines. Further, secondary resistance to nutlin was associated with deregulation of apoptosis-related genes and marked productive autophagy, the inhibition of which resulted in significant restoration of nutlin-induced cell death. Collectively, our findings argue that secondary resistance to nutlin in STS involved heterogeneous mechanisms resulting from clonal evolution and several biological pathways. Alternative dosing regimens and combination with other targeted agents are needed to achieve successful development of nutlin in the clinical setting. PMID:26427052

  8. Dominant mechanisms of primary resistance differ from dominant mechanisms of secondary resistance to targeted therapies.

    PubMed

    Asić, Ksenija

    2016-01-01

    The effectiveness of targeted therapies is currently limited, as almost all patients eventually acquire resistance within year/year and a half from therapy initiation and a small subset of a patients fail to respond at all, demonstrating intrinsic resistance. The aim of this review was to determine the potential common features and differences between the mechanisms of intrinsic and acquired resistance to targeted therapies by analyzing established resistance-generating alterations for ten FDA-approved targeted drugs. The frequency of alterations underlying intrinsic and acquired resistance shows distinctive pattern, where dominant mechanisms of intrinsic resistance include aberrations of signals downstream or upstream of the targeted protein and dominant mechanisms of acquired resistance refer to lesions in the target itself or alterations of signals at target-level that can mimic or compensate for target function. It appears that during the evolution of acquired resistance, the tumor cell is inclined to preserve the same oncogene addiction on a targeted protein it had prior to drug administration. On the other hand, intrinsic resistance develops early in tumorogenesis and is based on randomly selected mutated signals between targeted and non-targeted signaling pathways, leading to the acquisition of cancer hallmarks. In general, there is an overlap between the mechanisms of intrinsic and acquired resistance, but the occurrence frequency and distribution of alterations underlying intrinsic and acquired resistance to targeted therapies are significantly different. Focus should be placed on different group of genes in pursuing predictive markers for intrinsic and acquired resistance to targeted therapies. PMID:26364890

  9. Host adaptation to viruses relies on few genes with different cross-resistance properties

    PubMed Central

    Martins, Nelson E.; Faria, Vítor G.; Nolte, Viola; Schlötterer, Christian; Teixeira, Luis; Sucena, Élio; Magalhães, Sara

    2014-01-01

    Host adaptation to one parasite may affect its response to others. However, the genetics of these direct and correlated responses remains poorly studied. The overlap between these responses is instrumental for the understanding of host evolution in multiparasite environments. We determined the genetic and phenotypic changes underlying adaptation of Drosophila melanogaster to Drosophila C virus (DCV). Within 20 generations, flies selected with DCV showed increased survival after DCV infection, but also after cricket paralysis virus (CrPV) and flock house virus (FHV) infection. Whole-genome sequencing identified two regions of significant differentiation among treatments, from which candidate genes were functionally tested with RNAi. Three genes were validated—pastrel, a known DCV-response gene, and two other loci, Ubc-E2H and CG8492. Knockdown of Ubc-E2H and pastrel also led to increased sensitivity to CrPV, whereas knockdown of CG8492 increased susceptibility to FHV infection. Therefore, Drosophila adaptation to DCV relies on few major genes, each with different cross-resistance properties, conferring host resistance to several parasites. PMID:24711428

  10. Accomplishments of a 10-year initiative to develop host plant resistance to root-knot and reniform nematodes in cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2003 Cotton Incorporated initiated a Beltwide research program to develop host plant resistance against root-knot (Meloidogyne incognita) and reniform (Rotylenchulus reniformis) nematodes. Objectives formulated at a coordinating meeting in 2003 that included participants from public institutions...

  11. The bacterial DNA repair protein Mfd confers resistance to the host nitrogen immune response.

    PubMed

    Guillemet, Elisabeth; Leréec, Alain; Tran, Seav-Ly; Royer, Corinne; Barbosa, Isabelle; Sansonetti, Philippe; Lereclus, Didier; Ramarao, Nalini

    2016-01-01

    Production of reactive nitrogen species (NO) is a key step in the immune response following infections. NO induces lesions to bacterial DNA, thus limiting bacterial growth within hosts. Using two pathogenic bacteria, Bacillus cereus and Shigella flexneri, we show that the DNA-repair protein Mfd (Mutation-Frequency-Decline) is required for bacterial resistance to the host-NO-response. In both species, a mutant deficient for mfd does not survive to NO, produced in vitro or by phagocytic cells. In vivo, the ∆mfd mutant is avirulent and unable to survive the NO-stress. Moreover, NO induces DNA-double-strand-breaks and point mutations in the Δmfd mutant. In overall, these observations demonstrate that NO damages bacterial DNA and that Mfd is required to maintain bacterial genomic integrity. This unexpected discovery reveals that Mfd, a typical housekeeping gene, turns out to be a true virulence factor allowing survival and growth of the pathogen in its host, due to its capacity to protect the bacterium against NO, a key molecule of the innate immune defense. As Mfd is widely conserved in the bacterial kingdom, these data highlight a mechanism that may be used by a large spectrum of bacteria to overcome the host immune response and especially the mutagenic properties of NO. PMID:27435260

  12. The bacterial DNA repair protein Mfd confers resistance to the host nitrogen immune response

    PubMed Central

    Guillemet, Elisabeth; Leréec, Alain; Tran, Seav-Ly; Royer, Corinne; Barbosa, Isabelle; Sansonetti, Philippe; Lereclus, Didier; Ramarao, Nalini

    2016-01-01

    Production of reactive nitrogen species (NO) is a key step in the immune response following infections. NO induces lesions to bacterial DNA, thus limiting bacterial growth within hosts. Using two pathogenic bacteria, Bacillus cereus and Shigella flexneri, we show that the DNA-repair protein Mfd (Mutation-Frequency-Decline) is required for bacterial resistance to the host-NO-response. In both species, a mutant deficient for mfd does not survive to NO, produced in vitro or by phagocytic cells. In vivo, the ∆mfd mutant is avirulent and unable to survive the NO-stress. Moreover, NO induces DNA-double-strand-breaks and point mutations in the Δmfd mutant. In overall, these observations demonstrate that NO damages bacterial DNA and that Mfd is required to maintain bacterial genomic integrity. This unexpected discovery reveals that Mfd, a typical housekeeping gene, turns out to be a true virulence factor allowing survival and growth of the pathogen in its host, due to its capacity to protect the bacterium against NO, a key molecule of the innate immune defense. As Mfd is widely conserved in the bacterial kingdom, these data highlight a mechanism that may be used by a large spectrum of bacteria to overcome the host immune response and especially the mutagenic properties of NO. PMID:27435260

  13. Host-synthesized secondary compounds influence the in vitro interactions between fungal endophytes of maize.

    PubMed

    Saunders, Megan; Kohn, Linda M

    2008-01-01

    Maize produces a suite of allelopathic secondary metabolites, the benzoxazinoids. 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one and 2,4-dihydroxy-2H-1,4-benzoxazin-3-one reside as glucosides in plant tissue and spontaneously degrade to 6-methoxy-2-benzoxazolinone (MBOA) and 2-benzoxazolinone (BOA) upon plant cell disruption. Several maize-associated fungi in the genus Fusarium can metabolize MBOA and BOA. BOA tolerance levels in 10 species of Fusarium and in the maize endophytes Nigrospora oryzae, Acremonium zeae, and Periconia macrospinosa were characterized. BOA tolerance ranged from 0.25 to 1.10 mg/ml among species. The influence of substrate alteration by one species on the subsequent growth of another species was assessed in the presence and absence of BOA. The colony area of the secondary colonizer in heterospecific interactions was compared to that in autospecific interactions (one isolate follows itself). In the presence of BOA, four of six secondary colonizers had greater growth (facilitation) when primary colonizers had higher BOA tolerance than the secondary colonizer. When the primary colonizer had lower tolerance than the secondary, three of six secondary colonizers were inhibited (competition) and three not significantly affected. In BOA-free medium, the number of isolates that were facilitated or inhibited was the same regardless of the tolerance level of the primary colonizer. Two of six secondary colonizers were facilitated, two inhibited, and two not significantly affected. This study provides some support for facilitation in stressful conditions under the Menge-Sutherland model. The results are not consistent with the corresponding prediction of competition in the absence of stress. The hypothesis drawn from these data is that in the presence of a toxin, fungal species that detoxify their substrate can enhance the colonization rate of less tolerant fungi. PMID:17993551

  14. Host-Synthesized Secondary Compounds Influence the In Vitro Interactions between Fungal Endophytes of Maize▿

    PubMed Central

    Saunders, Megan; Kohn, Linda M.

    2008-01-01

    Maize produces a suite of allelopathic secondary metabolites, the benzoxazinoids. 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one and 2,4-dihydroxy-2H-1,4-benzoxazin-3-one reside as glucosides in plant tissue and spontaneously degrade to 6-methoxy-2-benzoxazolinone (MBOA) and 2-benzoxazolinone (BOA) upon plant cell disruption. Several maize-associated fungi in the genus Fusarium can metabolize MBOA and BOA. BOA tolerance levels in 10 species of Fusarium and in the maize endophytes Nigrospora oryzae, Acremonium zeae, and Periconia macrospinosa were characterized. BOA tolerance ranged from 0.25 to 1.10 mg/ml among species. The influence of substrate alteration by one species on the subsequent growth of another species was assessed in the presence and absence of BOA. The colony area of the secondary colonizer in heterospecific interactions was compared to that in autospecific interactions (one isolate follows itself). In the presence of BOA, four of six secondary colonizers had greater growth (facilitation) when primary colonizers had higher BOA tolerance than the secondary colonizer. When the primary colonizer had lower tolerance than the secondary, three of six secondary colonizers were inhibited (competition) and three not significantly affected. In BOA-free medium, the number of isolates that were facilitated or inhibited was the same regardless of the tolerance level of the primary colonizer. Two of six secondary colonizers were facilitated, two inhibited, and two not significantly affected. This study provides some support for facilitation in stressful conditions under the Menge-Sutherland model. The results are not consistent with the corresponding prediction of competition in the absence of stress. The hypothesis drawn from these data is that in the presence of a toxin, fungal species that detoxify their substrate can enhance the colonization rate of less tolerant fungi. PMID:17993551

  15. Host cell reactivation studies with epidermal cells of mice sensitive and resistant to carcinogenesis

    SciTech Connect

    Strickland, J.E.; Strickland, A.G.

    1984-03-01

    Primary epidermal cells from AKR, BALB/c, CD-1, and SENCAR mice, listed in order of least to most sensitive to epidermal carcinogenesis by initiation and promotion protocols, were found to be equally competent to ''reactivate'' herpes simplex virus type 1 irradiated by germicidal ultraviolet radiation. Nontumorigenic BALB/c epidermal cell lines selected in vitro for resistance to terminal differentiation after in vivo or in vitro treatment with initiating doses of carcinogens showed virus survival curves similar to those of primary cells. Similarly, primary cultures which were allowed to grow to confluency following a single treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (100 ng/ml) retained normal host cell reactivation. Host cell reactivation studies with mouse dermal fibroblasts could not be done because of the failure of the herpes simplex virus to infect these cells and produce plaques. These results demonstrate that survival of ultraviolet light-damaged virus in primary epidermal cells in culture is unrelated to whether the cells are derived from mice sensitive or resistant to epidermal carcinogenesis. Furthermore, virus survival is not changed by tumor promoter treatment or by treatment with initiating doses of carcinogens which results in differentiation-resistant cells.

  16. Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9

    PubMed Central

    Yoder, Kristine E.; Bundschuh, Ralf

    2016-01-01

    CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance. PMID:27404981

  17. Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9.

    PubMed

    Yoder, Kristine E; Bundschuh, Ralf

    2016-01-01

    CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance. PMID:27404981

  18. Adaptation of a plant pathogen to partial host resistance: selection for greater aggressiveness in grapevine downy mildew.

    PubMed

    Delmas, Chloé E L; Fabre, Frédéric; Jolivet, Jérôme; Mazet, Isabelle D; Richart Cervera, Sylvie; Delière, Laurent; Delmotte, François

    2016-06-01

    An understanding of the evolution of pathogen quantitative traits in response to host selective pressures is essential for the development of durable management strategies for resistant crops. However, we still lack experimental data on the effects of partial host resistance on multiple phenotypic traits (aggressiveness) and evolutionary strategies in pathogens. We performed a cross-inoculation experiment with four grapevine hosts and 103 isolates of grapevine downy mildew (Plasmopara viticola) sampled from susceptible and partially resistant grapevine varieties. We analysed the neutral and adaptive genetic differentiation of five quantitative traits relating to pathogen transmission. Isolates from resistant hosts were more aggressive than isolates from susceptible hosts, as they had a shorter latency period and higher levels of spore production. This pattern of adaptation contrasted with the lack of neutral genetic differentiation, providing evidence for directional selection. No specificity for a particular host variety was detected. Adapted isolates had traits that were advantageous on all resistant varieties. There was no fitness cost associated with this genetic adaptation, but several trade-offs between pathogen traits were observed. These results should improve the accuracy of prediction of fitness trajectories for this biotrophic pathogen, an essential element for the modelling of durable deployment strategies for resistant varieties. PMID:27247621

  19. Overcoming Resistance to Achievement-based Unit Grading in Secondary Physical Education

    ERIC Educational Resources Information Center

    Johnson, Randall

    2008-01-01

    Achievement-based unit grading in secondary physical education is not commonly practiced due to resistance to grading students based on learning, performance, or achievement. Traditional grading practices based on managerial factors, such as attendance and good behavior, and on "pseudo-accountability" do little to make students accountable for…

  20. A Piece of Resistance: Exploring Behaviour Assessment and Political Subjectification in a Swedish Upper Secondary School

    ERIC Educational Resources Information Center

    Larsson, Joakim

    2014-01-01

    In 2007, students at a Swedish Upper Secondary School engaged in a series of protests and demonstrations against the implementation of a written assessment of student conduct. This article explores the motivations and manifestations of this resistance, mainly by analysing debate articles and web material from the student union that organized the…

  1. Sialic acids in different Leishmania sp., its correlation with nitric oxide resistance and host responses.

    PubMed

    Ghoshal, Angana; Gerwig, Gerrit J; Kamerling, Johannis P; Mandal, Chitra

    2010-05-01

    The presence of different derivatives of sialic acids (SA) on Leishmania donovani instigated us to investigate their status on different strains of Leishmania sp. causing different forms of the disease. Leishmania tropica (K27), Leishmania major (JISH118) and Leishmania mexicana (LV4) responsible for cutaneous, Leishmania braziliensis (L280) and Leishmania amazonensis (LV81) causing diffuse and Leishmania infantum (MON29) responsible for visceral leishmaniasis were included in this study. The strains showed a differential distribution of SA in spite of their close resemblance in pathogenesis. K27, JISH118, L280 and MON29 were categorized as high SA-containing strains having enhanced 9-O-acetyl sialic acid (9-O-AcSA(high)) whereas LV4 and LV81 evidenced considerably reduced SA. Interestingly, 9-O-AcSA(high) promastigotes showed significant viability as compared to their de-O-acetylated forms after exposure to NaNO(2) suggesting the involvement of 9-O-AcSA in conferring nitric oxide (NO) resistance. Enhanced intracellular survivability was demonstrated following infection of human macrophages with 9-O-AcSA(high) promastigotes in contrast to their de-O-acetylated forms indicating their contribution in bestowing a survival benefit. Additionally, reduced accumulation of NO, interleukin-12 and interferon-gamma in the supernatant of macrophages infected with 9-O-AcSA(high) promastigotes indicated suppression of leishmanicidal host responses. However, LV4 and LV81 with least 9-O-AcSA, before and after de-O-acetylation, showed unaltered NO resistance, multiplicity and host responses signifying the probable involvement of other determinants which may be a function of their inherent parasitic attribute. Hence, enhanced levels of 9-O-AcSA serve as one of the potential determinants responsible for increased NO resistance and survivability of parasites by inhibition of host responses. PMID:20085901

  2. Host-Mediated Bioactivation of Pyrazinamide: Implications for Efficacy, Resistance, and Therapeutic Alternatives

    PubMed Central

    Via, Laura E.; Savic, Rada; Weiner, Danielle M.; Zimmerman, Matthew D.; Prideaux, Brendan; Irwin, Scott M.; Lyon, Eddie; O’Brien, Paul; Gopal, Pooja; Eum, Seokyong; Lee, Myungsun; Lanoix, Jean-Philippe; Dutta, Noton K.; Shim, TaeSun; Cho, Jeong Su; Kim, Wooshik; Karakousis, Petros C.; Lenaerts, Anne; Nuermberger, Eric; Barry, Clifton E.; Dartois, Véronique

    2015-01-01

    Pyrazinamide has played a critical role in shortening therapy against drug-sensitive, drug-resistant, active, and latent tuberculosis (TB). Despite widespread recognition of its therapeutic importance, the sterilizing properties of this 60-year-old drug remain an enigma given its rather poor activity in vitro. Here we revisit longstanding paradigms and offer pharmacokinetic explanations for the apparent disconnect between in vitro activity and clinical impact. We show substantial host-mediated conversion of prodrug pyrazinamide (PZA) to the active form, pyrazinoic acid (POA), in TB patients and in animal models. We demonstrate favorable penetration of this pool of circulating POA from plasma into lung tissue and granulomas, where the pathogen resides. In standardized growth inhibition experiments, we show that POA exhibits superior in vitro potency compared to PZA, indicating that the vascular supply of host-derived POA may contribute to the in vivo efficacy of PZA, thereby reducing the apparent discrepancy between in vitro and in vivo activity. However, the results also raise the possibility that subinhibitory concentrations of POA generated by the host could fuel the emergence of resistance to both PZA and POA. In contrast to widespread expectations, we demonstrate good oral bioavailability and exposure in preclinical species in pharmacokinetic studies of oral POA. Baseline exposure of oral POA can be further increased by the xanthine oxidase inhibitor and approved gout drug allopurinol. These promising results pave the way for clinical investigations of oral POA as a therapeutic alternative or an add-on to overcome PZA resistance and salvage this essential TB drug. PMID:26086040

  3. Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor

    PubMed Central

    Gounder, Mrinal M.

    2012-01-01

    Small molecule kinase inhibitors have irrevocably altered cancer treatment. March 2010 marks the 10th anniversary of using imatinib in gastrointestinal stromal tumors (GIST), a cardinal example of the utility of such targeted therapy in a solid tumor. Before imatinib, metastatic GIST was frustrating to treat due to its resistance to standard cytotoxic chemotherapy. Median survival for patients with metastatic GIST improved from 19 to 60 months with imatinib. In treating patients with GIST, two patterns of tyrosine kinase inhibitor resistance have been observed. In the first, ~9–14% of patients have progression within 3 months of starting imatinib. These patients are classified as having primary or early resistance. Median progression-free survival (PFS) on imatinib is approximately 24 months; patients with later progression are classified as having secondary or acquired resistance. Primary studies and a meta-analysis of studies of imatinib in GIST patients have identified prognostic features that contribute to treatment failure. One of the strongest predictors for success of therapy is KIT or PDGFRA mutational status. Patients with KIT exon 11 mutant GIST have better response rates, PFS, and overall survival compared to other mutations. A great deal has been learned in the last decade about sensitivity and resistance of GIST to imatinib; however, many unanswered questions remain about secondary resistance mechanisms and clinical management in the third- and fourth-line setting. This review will discuss the role of dose effects, and early and late resistance to imatinib and their clinical implications. Patients intolerant to imatinib (5%) and those who progress on imatinib are treated with sunitinib. The mechanism of resistance to sunitinib is unknown at this time but is also appears related to growth of clones with secondary mutations in KIT. Third- and fourth-line treatments of GIST and with future treatment strategies are also discussed. PMID:21116624

  4. Temporal and Anatomical Host Resistance to Chronic Salmonella Infection Is Quantitatively Dictated by Nramp1 and Influenced by Host Genetic Background

    PubMed Central

    Loomis, Wendy P.; Johnson, Matthew L.; Brasfield, Alicia; Blanc, Marie-Pierre; Yi, Jaehun; Miller, Samuel I.; Cookson, Brad T.; Hajjar, Adeline M.

    2014-01-01

    The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS). NTS-susceptible C57BL/6 (B6) mice, which express the mutant Nramp1D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1G169 from resistant A/J mice (Nramp-Cg) or overexpressing Nramp1G169 from a transgene (Nramp-Tg), conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2–3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg) provided greater protection as indicated by decreased splenic bacterial colonization (Tghost resistance is conferred by Nramp1 expression in NTS-susceptible mice, 2) restriction of systemic bacterial growth in the spleens of NTS-susceptible mice is enhanced by Nramp1 expression and dose-dependent, and 3) host genes other than Nramp1 also contribute to the ability of NTS-resistant 129×1/SvJ mice to control bacterial replication during chronic infection. PMID:25350459

  5. Inoculation of Transgenic Resistant Potato by Phytophthora infestans Affects Host Plant Choice of a Generalist Moth.

    PubMed

    Abreha, Kibrom B; Alexandersson, Erik; Vossen, Jack H; Anderson, Peter; Andreasson, Erik

    2015-01-01

    Pathogen attack and the plant's response to this attack affect herbivore oviposition preference and larval performance. Introduction of major resistance genes against Phytophthora infestans (Rpi-genes), the cause of the devastating late blight disease, from wild Solanum species into potato changes the plant-pathogen interaction dynamics completely, but little is known about the effects on non-target organisms. Thus, we examined the effect of P. infestans itself and introduction of an Rpi-gene into the crop on host plant preference of the generalist insect herbivore, Spodoptera littoralis (Lepidoptera: Noctuidae). In two choice bioassays, S. littoralis preferred to oviposit on P. infestans-inoculated plants of both the susceptible potato (cv. Desiree) and an isogenic resistant clone (A01-22: cv. Desiree transformed with Rpi-blb1), when compared to uninoculated plants of the same genotype. Both cv. Desiree and clone A01-22 were equally preferred for oviposition by S. littoralis when uninoculated plants were used, while cv. Desiree received more eggs compared to the resistant clone when both were inoculated with the pathogen. No significant difference in larval and pupal weight was found between S. littoralis larvae reared on leaves of the susceptible potato plants inoculated or uninoculated with P. infestans. Thus, the herbivore's host plant preference in this system was not directly associated with larval performance. The results indicate that the Rpi-blb1 based resistance in itself does not influence insect behavior, but that herbivore oviposition preference is affected by a change in the plant-microbe interaction. PMID:26053171

  6. When virulence originates from nonagricultural hosts: evolutionary and epidemiological consequences of introgressions following secondary contacts in Venturia inaequalis.

    PubMed

    Leroy, Thibault; Caffier, Valérie; Celton, Jean-Marc; Anger, Nicolas; Durel, Charles-Eric; Lemaire, Christophe; Le Cam, Bruno

    2016-06-01

    In pathogens, introgressions through secondary contacts between divergent populations from agricultural and nonagricultural disease reservoirs are expected to have crucial evolutionary and epidemiological implications. Despite the importance of this question for disease management, experimental demonstrations of these implications remain scarce. Recently, we identified a virulent population of the apple scab pathogen Venturia inaequalis that migrated from nonagricultural hosts to European domestic apple orchards. Here, we investigated the occurrence of gene flow between agricultural and nonagricultural populations sampled in two orchards, and thereafter its consequences on the pathogenicity of hybrids. Population genetic structure and demographic inferences based on the genotypes of 104 strains revealed a high amount of gene flow between the two populations in one orchard. In this site, mating between populations was made possible by the presence of a common host. Our results revealed an invasion of the virulent trait in the agricultural population; a main direction of introgression in hybrids from the agricultural to nonagricultural genetic backgrounds; and a population of hybrids with transgressive traits. We demonstrate a secondary contact with gene flow between divergent populations of pathogens. Our findings highlight evolutionary and epidemiological changes in pathogens and have concrete implications for sustainable disease management. PMID:26853715

  7. Use of refuse in host plant resistance systems for the control of virulent biotype adaptation in the soybean aphid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Host plant resistant (HPR) soybean varieties have the potential to offer economic control of the soybean aphid (Aphis glycines). However, virulent aphid biotypes capable of overcoming plant resistance have caused challenges for the integration of HPR. The widespread planting of HPR soybean would inc...

  8. Splice variants and regulatory networks associated with host resistance to the intestinal worm Cooperia oncophora in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To elucidate the molecular mechanisms of host resistance, we characterized the jejunal transcriptome of Angus cattle selected for parasite resistance for over 20 years in response to infection caused by the intestinal worm Cooperia oncophora. The transcript abundance of 56 genes, such as that of muc...

  9. Genetic control of host resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection.

    PubMed

    Lunney, Joan K; Chen, Hongbo

    2010-12-01

    This manuscript focuses on the advances made using genomic approaches to identify biomarkers that define genes and pathways that are correlated with swine resistance to infection with porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important swine viral pathogen worldwide. International efforts are underway to assess resistance and susceptibility to infectious pathogens using tools such as gene arrays, single nucleotide polymorphisms (SNPs) chips, genome-wide association studies (GWAS), proteomics, and advanced bioinformatics. These studies should identify new candidate genes and biological pathways associated with host PRRS resistance and alternate viral disease processes and mechanisms; they may unveil biomarkers that account for genetic control of PRRS or, alternately, that reveal new targets for therapeutics or vaccines. Previous genomic approaches have expanded our understanding of quantitative trait loci (QTL) controlling traits of economic importance in pig production, e.g., feed efficiency, meat production, leanness; only recently have these included health traits and disease resistance. Genomic studies should have substantial impact for the pig industry since it is now possible to include the use of biomarkers for basic health traits alongside broader set of markers utilized for selection of pigs for improved performance and reproductive traits, as well as pork quality. Additionally these studies may reveal alternate PRRS control mechanisms that can be exploited for novel drugs, biotherapeutics and vaccine designs. PMID:20709118

  10. [Antibiotic resistance of bacteria to 6 antibiotics in secondary effluents of municipal wastewater treatment plants].

    PubMed

    Lu, Sun-Qin; Li, Yi; Huang, Jing-Jing; Wei, Bin; Hu, Hong-Ying

    2011-11-01

    Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned as an emerging contaminant. To estimate antibiotic resistance in secondary effluents of municipal wastewater treatment plants, antibiotic tolerance of heterotrophic bacteria, proportion of antibiotic-resistant bacteria and hemi-inhibitory concentrations of six antibiotics (penicillin, ampicillin, cefalexin, chloramphenicol, tetracycline and rifampicin) were determined at two wastewater treatment plants (WWTPs) in Beijing. The results showed that proportions of ampicillin-resistant bacteria in WWTP-G and chloramphenicol-resistant bacteria in WWTP-Q were highest to 59% and 44%, respectively. The concentrations of ampicillin-resistant bacteria in the effluents of WWTP-G and WWTP-Q were as high as 4.0 x 10(3) CFU x mL(-1) and 3.5 x 10(4) CFU x mL(-1), respectively; the concentrations of chloramphenicol-resistant bacteria were 4.9 x 10(2) CFU x mL(-1) and 4.6 x 10(4) CFU x mL(-1), respectively. The data also indicated that the hemi-inhibitory concentrations of heterotrophic bacteria to 6 antibiotics were much higher than common concentrations of antibiotics in sewages, which suggested that antibiotic-resistant bacteria could exist over a long period in the effluents with low concentrations of antibiotics. Antibiotic-resistant bacteria could be a potential microbial risk during sewage effluent reuse or emission into environmental waters. PMID:22295644

  11. Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis.

    PubMed

    Zumla, Alimuddin; Rao, Martin; Dodoo, Ernest; Maeurer, Markus

    2016-01-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication of M. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation. PMID:27301245

  12. Human host defense peptide LL-37 stimulates virulence factor production and adaptive resistance in Pseudomonas aeruginosa.

    PubMed

    Strempel, Nikola; Neidig, Anke; Nusser, Michael; Geffers, Robert; Vieillard, Julien; Lesouhaitier, Olivier; Brenner-Weiss, Gerald; Overhage, Joerg

    2013-01-01

    A multitude of different virulence factors as well as the ability to rapidly adapt to adverse environmental conditions are important features for the high pathogenicity of Pseudomonas aeruginosa. Both virulence and adaptive resistance are tightly controlled by a complex regulatory network and respond to external stimuli, such as host signals or antibiotic stress, in a highly specific manner. Here, we demonstrate that physiological concentrations of the human host defense peptide LL-37 promote virulence factor production as well as an adaptive resistance against fluoroquinolone and aminoglycoside antibiotics in P. aeruginosa PAO1. Microarray analyses of P. aeruginosa cells exposed to LL-37 revealed an upregulation of gene clusters involved in the production of quorum sensing molecules and secreted virulence factors (PQS, phenazine, hydrogen cyanide (HCN), elastase and rhamnolipids) and in lipopolysaccharide (LPS) modification as well as an induction of genes encoding multidrug efflux pumps MexCD-OprJ and MexGHI-OpmD. Accordingly, we detected significantly elevated levels of toxic metabolites and proteases in bacterial supernatants after LL-37 treatment. Pre-incubation of bacteria with LL-37 for 2 h led to a decreased susceptibility towards gentamicin and ciprofloxacin. Quantitative Realtime PCR results using a PAO1-pqsE mutant strain present evidence that the quinolone response protein and virulence regulator PqsE may be implicated in the regulation of the observed phenotype in response to LL-37. Further experiments with synthetic cationic antimicrobial peptides IDR-1018, 1037 and HHC-36 showed no induction of pqsE expression, suggesting a new role of PqsE as highly specific host stress sensor. PMID:24349231

  13. Human Host Defense Peptide LL-37 Stimulates Virulence Factor Production and Adaptive Resistance in Pseudomonas aeruginosa

    PubMed Central

    Strempel, Nikola; Neidig, Anke; Nusser, Michael; Geffers, Robert; Vieillard, Julien; Lesouhaitier, Olivier; Brenner-Weiss, Gerald; Overhage, Joerg

    2013-01-01

    A multitude of different virulence factors as well as the ability to rapidly adapt to adverse environmental conditions are important features for the high pathogenicity of Pseudomonas aeruginosa. Both virulence and adaptive resistance are tightly controlled by a complex regulatory network and respond to external stimuli, such as host signals or antibiotic stress, in a highly specific manner. Here, we demonstrate that physiological concentrations of the human host defense peptide LL-37 promote virulence factor production as well as an adaptive resistance against fluoroquinolone and aminoglycoside antibiotics in P. aeruginosa PAO1. Microarray analyses of P. aeruginosa cells exposed to LL-37 revealed an upregulation of gene clusters involved in the production of quorum sensing molecules and secreted virulence factors (PQS, phenazine, hydrogen cyanide (HCN), elastase and rhamnolipids) and in lipopolysaccharide (LPS) modification as well as an induction of genes encoding multidrug efflux pumps MexCD-OprJ and MexGHI-OpmD. Accordingly, we detected significantly elevated levels of toxic metabolites and proteases in bacterial supernatants after LL-37 treatment. Pre-incubation of bacteria with LL-37 for 2 h led to a decreased susceptibility towards gentamicin and ciprofloxacin. Quantitative Realtime PCR results using a PAO1-pqsE mutant strain present evidence that the quinolone response protein and virulence regulator PqsE may be implicated in the regulation of the observed phenotype in response to LL-37. Further experiments with synthetic cationic antimicrobial peptides IDR-1018, 1037 and HHC-36 showed no induction of pqsE expression, suggesting a new role of PqsE as highly specific host stress sensor. PMID:24349231

  14. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors

    PubMed Central

    Sasaki, Takaaki; Koivunen, Jussi; Ogino, Atsuko; Yanagita, Masahiko; Nikiforow, Sarah; Zheng, Wei; Lathan, Christopher; Marcoux, J. Paul; Du, Jinyan; Okuda, Katsuhiro; Capelletti, Marzia; Shimamura, Takeshi; Ercan, Dalia; Stumpfova, Magda; Xiao, Yun; Weremowicz, Stanislawa; Butaney, Mohit; Heon, Stephanie; Wilner, Keith; Christensen, James G.; Eck, Michel J.; Wong, Kwok-Kin; Lindeman, Neal; Gray, Nathanael S.; Rodig, Scott J.; Jänne, Pasi A.

    2011-01-01

    Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers. However, their efficacy will ultimately be limited by the development of acquired drug resistance. Here we report two mechanisms of ALK TKI resistance identified from, a crizotinib treated non-small cell lung cancer (NSCLC) patient and in a cell line generated from the resistant tumor (DFCI076), and from studying a resistant version of the ALK TKI (TAE684) sensitive H3122 cell line. The crizotinib resistant DFCI076 cell line, harboured a unique L1152R ALK secondary mutation, and was also resistant to the structurally unrelated ALK TKI TAE684. Although the DFCI076 cell line was still partially dependent on ALK for survival, it also contained concurrent co-activation of epidermal growth factor receptor (EGFR) signalling. In contrast, the TAE684 resistant (TR3) H3122 cell line did not contain an ALK secondary mutation but instead harboured co-activation of EGFR signalling. Dual inhibition of both ALK and EGFR was the most effective therapeutic strategy for the DFCI076 and H3122 TR3 cell lines. We further identified a subset (3/50; 6%) of treatment naïve NSCLC patients with ALK rearrangements that also had concurrent EGFR activating mutations. Our studies identify resistance mechanisms to ALK TKIs mediated by both ALK and by a bypass signalling pathway mediated by EGFR. These mechanisms can occur independently, or in the same cancer, suggesting that the combination of both ALK and EGFR inhibitors may represent an effective therapy for these subsets of NSCLC patients. PMID:21791641

  15. Extreme resistance as a host counter-counter defense against viral suppression of RNA silencing.

    PubMed

    Sansregret, Raphaël; Dufour, Vanessa; Langlois, Mathieu; Daayf, Fouad; Dunoyer, Patrice; Voinnet, Olivier; Bouarab, Kamal

    2013-01-01

    RNA silencing mediated by small RNAs (sRNAs) is a conserved regulatory process with key antiviral and antimicrobial roles in eukaryotes. A widespread counter-defensive strategy of viruses against RNA silencing is to deploy viral suppressors of RNA silencing (VSRs), epitomized by the P19 protein of tombusviruses, which sequesters sRNAs and compromises their downstream action. Here, we provide evidence that specific Nicotiana species are able to sense and, in turn, antagonize the effects of P19 by activating a highly potent immune response that protects tissues against Tomato bushy stunt virus infection. This immunity is salicylate- and ethylene-dependent, and occurs without microscopic cell death, providing an example of "extreme resistance" (ER). We show that the capacity of P19 to bind sRNA, which is mandatory for its VSR function, is also necessary to induce ER, and that effects downstream of P19-sRNA complex formation are the likely determinants of the induced resistance. Accordingly, VSRs unrelated to P19 that also bind sRNA compromise the onset of P19-elicited defense, but do not alter a resistance phenotype conferred by a viral protein without VSR activity. These results show that plants have evolved specific responses against the damages incurred by VSRs to the cellular silencing machinery, a likely necessary step in the never-ending molecular arms race opposing pathogens to their hosts. PMID:23785291

  16. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    PubMed

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  17. Apparent Acquired Resistance by a Weevil to Its Parasitoid Is Influenced by Host Plant.

    PubMed

    Goldson, Stephen L; Tomasetto, Federico

    2016-01-01

    Field parasitism rates of the Argentine stem weevil Listronotus bonariensis (Kuschel; Coleoptera: Curculionidae) by Microctonus hyperodae Loan (Hymenoptera: Braconidae) are known to vary according to different host Lolium species that also differ in ploidy. To further investigate this, a laboratory study was conducted to examine parasitism rates on tetraploid Italian Lolium multiflorum, diploid Lolium perenne and diploid hybrid L. perenne ×L. multiflorum; none of which were infected by Epichloë endophyte. At the same time, the opportunity was taken to compare the results of this study with observations made during extensive laboratory-based research and parasitoid-rearing in the 1990s using the same host plant species. This made it possible to determine whether there has been any change in weevil susceptibility to the parasitoid over a 20 year period when in the presence of the tetraploid Italian, diploid perennial and hybrid host grasses that were commonly in use in the 1990's. The incidence of parasitism in cages, in the presence of these three grasses mirrored what has recently been observed in the field. When caged, weevil parasitism rates in the presence of a tetraploid Italian ryegrass host were significantly higher (75%) than rates that occurred in the presence of either the diploid perennial (46%) or the diploid hybrid (52%) grass, which were not significantly different from each other. This is very different to laboratory parasitism rates in the 1990s when in the presence of both of the latter grasses high rates of parasitism (c. 75%) were recorded. These high rates are typical of those still found in weevils in the presence of both field and caged tetraploid Italian grasses. In contrast, the abrupt decline in weevil parasitism rates points to the possibility of evolved resistance by the weevil to the parasitoid in the diploid and hybrid grasses, but not so in the tetraploid. The orientation of plants in the laboratory cages had no significant effect on

  18. Apparent Acquired Resistance by a Weevil to Its Parasitoid Is Influenced by Host Plant

    PubMed Central

    Goldson, Stephen L.; Tomasetto, Federico

    2016-01-01

    Field parasitism rates of the Argentine stem weevil Listronotus bonariensis (Kuschel; Coleoptera: Curculionidae) by Microctonus hyperodae Loan (Hymenoptera: Braconidae) are known to vary according to different host Lolium species that also differ in ploidy. To further investigate this, a laboratory study was conducted to examine parasitism rates on tetraploid Italian Lolium multiflorum, diploid Lolium perenne and diploid hybrid L. perenne ×L. multiflorum; none of which were infected by Epichloë endophyte. At the same time, the opportunity was taken to compare the results of this study with observations made during extensive laboratory-based research and parasitoid-rearing in the 1990s using the same host plant species. This made it possible to determine whether there has been any change in weevil susceptibility to the parasitoid over a 20 year period when in the presence of the tetraploid Italian, diploid perennial and hybrid host grasses that were commonly in use in the 1990’s. The incidence of parasitism in cages, in the presence of these three grasses mirrored what has recently been observed in the field. When caged, weevil parasitism rates in the presence of a tetraploid Italian ryegrass host were significantly higher (75%) than rates that occurred in the presence of either the diploid perennial (46%) or the diploid hybrid (52%) grass, which were not significantly different from each other. This is very different to laboratory parasitism rates in the 1990s when in the presence of both of the latter grasses high rates of parasitism (c. 75%) were recorded. These high rates are typical of those still found in weevils in the presence of both field and caged tetraploid Italian grasses. In contrast, the abrupt decline in weevil parasitism rates points to the possibility of evolved resistance by the weevil to the parasitoid in the diploid and hybrid grasses, but not so in the tetraploid. The orientation of plants in the laboratory cages had no significant effect

  19. Nitric oxide production during murine Lyme disease: lack of involvement in host resistance or pathology.

    PubMed Central

    Seiler, K P; Vavrin, Z; Eichwald, E; Hibbs, J B; Weis, J J

    1995-01-01

    The murine model of Lyme disease was used to determine the role of inflammatory induced nitric oxide (NO) during infection by the spirochete Borrelia burgdorferi. The outer surface lipoproteins of B. burgdorferi are potent stimulators of inflammatory cytokines and NO production by cultured macrophages in vitro. The addition of NO to cultures of B. burgdorferi prevents growth, suggesting a protective role of NO for the infected host. NO is also a crucial effector in some models of arthritis. Therefore, the involvement of NO in controlling B. burgdorferi infection and its participation in pathological development of arthritis were investigated. Both mildly arthritic (BALB/c) and severely arthritic (C3H/HeJ) strains of mice systemically produced high levels of NO 1 week after infection with B. burgdorferi, as determined by urinary nitrate. NO production remained high throughout the infection in BALB/c mice, while in C3H/HeJ mice NO production returned rapidly to uninfected levels. The in vivo inhibitor of the NO synthase enzyme NG-L-monomethyl arginine (LMMA) was given to mice to investigate whether decreasing NO production would alter the course of disease. LMMA effectively blocked NO production in infected mice; however, there was no significant difference in arthritis development, spirochete infection of tissues, or production of specific antibody in LMMA-treated mice. These results indicate that B. burgdorferi is able to persist in the host even in the presence of high levels of NO. Furthermore, NO is not involved in the control of spirochete infection of tissues, nor is it involved in the development of arthritis. The potent activity of NO against intracellular pathogens and the in vivo resistance of B. burgdorferi to NO suggest that this organism is not located in an intracellular compartment during an essential portion of its infection of the mammalian host. PMID:7558296

  20. Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection

    PubMed Central

    Silva-Gomes, Sandro; Appelberg, Rui; Larsen, Rasmus; Soares, Miguel Parreira

    2013-01-01

    Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (Mϕ) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1−/−) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1+/+) controls. Furthermore, Hmox1−/− mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1−/− versus Hmox1+/+ SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected Mϕ, an effect mimicked by exogenous heme administration to M. avium-infected wild-type Mϕ in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in Mϕ, contributing critically to host resistance to Mycobacterium infection. PMID:23630967

  1. Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma

    PubMed Central

    WANG, TING-CHUNG; CHENG, CHUN-YU; YANG, WEI-HSUN; CHEN, WEN-CHENG; CHANG, PEY-JIUM

    2015-01-01

    The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life-threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague-Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma. PMID:26299849

  2. The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience.

    PubMed

    Ferrandon, Dominique

    2013-02-01

    Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs). PMID:23228366

  3. Impaired host resistance to endotoxin and malaria in polychlorinated biphenyl- and hexachlorobenzene-treated mice.

    PubMed Central

    Loose, L D; Silkworth, J B; Pittman, K A; Benitz, K F; Mueller, W

    1978-01-01

    The in vivo effect of polychlorinated biphenyl (PCB) and hexachlorobenzene (HCB) on murine endotoxin sensitivity and resistance to malaria (Plasmodium berghei NYU-2) infection was studied. The dietary administration of 167 ppm (167 microgram/g) of PCB 1242 or HCB for 3 weeks resulted in an enhanced sensitivity to gram-negative endotoxin (Salmonella typhosa), which was further increased in animals maintained on the diets for 6 weeks. By 6 weeks, a 5.2- or 32-fold increase in endotoxin sensitivity was seen in mice fed PCB or HCB, respectively. A 20% decrease in mean survival time of mice fed PCB 1242 for 3 or 6 weeks and inoculated with malaria was demonstrated. Infected mice that received HCB for 3 or 6 weeks manifested a reduction in mean survival time of 24 or 31%, respectively. Histopathological examination revealed a normal thymus, spleen, mesenteric lymph nodes, and lungs. Centrilobular and pericentral hepatocyte hypertrophy, common to organochlorine exposure, was observed. Electron capture gas chromatographic analysis for PCB 1242 or HCB in the tissues examined histologically revealed a significant deposit of the xenobiotics. HCB concentration was approximately 16 to 25 times greater than that of PCB. The data indicate that environmental chemicals impair host resistance and that the alteration may be related to the presence of the chemicals in the lymphoreticular organs. PMID:97225

  4. Elucidation of virus-host interactions to enhance resistance breeding for control of virus diseases in potato

    PubMed Central

    Valkonen, Jari P.T.

    2015-01-01

    Potato virus Y (PVY) and Potato mop-top virus (PMTV) are viruses whose geographical distribution is expanding and economic losses are increasing, in contrast to most of other viruses infecting potato crops. Most potato cultivars lack broad-spectrum resistance to the new, genetically complex strains of PVY, and no efficient resistance to PMTV is known in potato. Control of the vectors of these viruses is not an efficient or possible strategy to prevent infections. Studies on molecular virus-host interactions can discover plant genes that are important to viral infection or antiviral defence. Both types of genes may be utilized in resistance breeding, which is discussed in this paper. The advanced gene technologies provide means to fortify potato cultivars with effective virus resistance genes or mutated, non-functional host factors that interfere with virus infection. PMID:25931981

  5. Molecular mapping of a non-host resistance gene YrpstY1 in barley (Hordeum vulgare L.) for resistance to wheat stripe rust.

    PubMed

    Sui, Xinxia; He, Zhonghu; Lu, Yaming; Wang, Zhenlin; Xia, Xianchun

    2010-10-01

    Cultivated barley (Hordeum vulgare L.) is considered as a non-host or inappropriate host species for wheat stripe rust caused by Puccinia striiformis f. sp. tritici. Most barley cultivars show a broad-spectrum resistance to wheat stripe rust. To determine the genes for resistance to wheat stripe rust in barley, a cross was made between a resistant barley line Y12 and a susceptible line Y16. The two parents, F(1) and 147 BC(1) plants were tested at seedling stage with Chinese prevalent race CYR32 of Puccinia striiformis f. sp. tritici by artificial inoculation in greenhouse. The results indicated that Y12 possessed one dominant resistance gene to wheat stripe rust, designated YrpstY1 provisionally. A total of 388 simple sequence repeat (SSR) markers were used to map the resistance gene in Y12 using bulked segregant analysis. A linkage map, including nine SSR loci on chromosome 7H and YrpstY1, was constructed using the BC(1) population, indicating that the resistance gene YrpstY1 is located on chromosome 7H. It is potential to transfer the resistance gene into common wheat for stripe rust resistance. PMID:21039455

  6. Toward elucidation of genetic and functional genetic mechanisms in corn host resistance to Aspergillus flavus infection and aflatoxin contamination.

    PubMed

    Shan, Xueyan; Williams, W Paul

    2014-01-01

    Aflatoxins are carcinogenic mycotoxins produced by some species in the Aspergillus genus, such as A. flavus and A. parasiticus. Contamination of aflatoxins in corn profusely happens at pre-harvest stage when heat and drought field conditions favor A. flavus colonization. Commercial corn hybrids are generally susceptible to A. flavus infection. An ideal strategy for preventing aflatoxin contamination is through the enhancement of corn host resistance to Aspergillus infection and aflatoxin production. Constant efforts have been made by corn breeders to develop resistant corn genotypes. Significantly low levels of aflatoxin accumulation have been determined in certain resistant corn inbred lines. A number of reports of quantitative trait loci have provided compelling evidence supporting the quantitative trait genetic basis of corn host resistance to aflatoxin accumulation. Important findings have also been obtained from the investigation on candidate resistance genes through transcriptomics approach. Elucidation of molecular mechanisms will provide in-depth understanding of the host-pathogen interactions and hence facilitate the breeding of corn with resistance to A. flavus infection and aflatoxin accumulation. PMID:25101068

  7. The role of the secondary cell wall in plant resistance to pathogens.

    PubMed

    Miedes, Eva; Vanholme, Ruben; Boerjan, Wout; Molina, Antonio

    2014-01-01

    Plant resistance to pathogens relies on a complex network of constitutive and inducible defensive barriers. The plant cell wall is one of the barriers that pathogens need to overcome to successfully colonize plant tissues. The traditional view of the plant cell wall as a passive barrier has evolved to a concept that considers the wall as a dynamic structure that regulates both constitutive and inducible defense mechanisms, and as a source of signaling molecules that trigger immune responses. The secondary cell walls of plants also represent a carbon-neutral feedstock (lignocellulosic biomass) for the production of biofuels and biomaterials. Therefore, engineering plants with improved secondary cell wall characteristics is an interesting strategy to ease the processing of lignocellulosic biomass in the biorefinery. However, modification of the integrity of the cell wall by impairment of proteins required for its biosynthesis or remodeling may impact the plants resistance to pathogens. This review summarizes our understanding of the role of the plant cell wall in pathogen resistance with a focus on the contribution of lignin to this biological process. PMID:25161657

  8. The role of the secondary cell wall in plant resistance to pathogens

    PubMed Central

    Miedes, Eva; Vanholme, Ruben; Boerjan, Wout; Molina, Antonio

    2014-01-01

    Plant resistance to pathogens relies on a complex network of constitutive and inducible defensive barriers. The plant cell wall is one of the barriers that pathogens need to overcome to successfully colonize plant tissues. The traditional view of the plant cell wall as a passive barrier has evolved to a concept that considers the wall as a dynamic structure that regulates both constitutive and inducible defense mechanisms, and as a source of signaling molecules that trigger immune responses. The secondary cell walls of plants also represent a carbon-neutral feedstock (lignocellulosic biomass) for the production of biofuels and biomaterials. Therefore, engineering plants with improved secondary cell wall characteristics is an interesting strategy to ease the processing of lignocellulosic biomass in the biorefinery. However, modification of the integrity of the cell wall by impairment of proteins required for its biosynthesis or remodeling may impact the plants resistance to pathogens. This review summarizes our understanding of the role of the plant cell wall in pathogen resistance with a focus on the contribution of lignin to this biological process. PMID:25161657

  9. Development of Host-Plant Resistance as a Strategy to Reduce Damage from the Major Sunflower Insect Pests

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The major insect pests attacking cultivated sunflower include the sunflower stem weevil, the sunflower moth, the red sunflower seed weevil, the banded sunflower moth, and the sunflower midge. Strategies to reduce crop losses for these pests have focused on insecticidal control, but host-plant resist...

  10. Identification of maize genes associated with host plant resistance and susceptibility to Aspergillus flavus infection and aflatoxin accumulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus infection and aflatoxin contamination of maize pose negative impacts in agriculture and health. Commercial maize hybrids are generally susceptible to this fungus. Significant levels of host plant resistance have been observed in certain maize inbred lines. This study was conducted...

  11. Accomplishments of a 10-year initiative to develop host plant resistance to root-knot and reniform nematodes in cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2003 Cotton Incorporated initiated a Beltwide research program to develop host plant resistance to root-knot (Meloidogyne incognita) and reniform (Rotylenchulus reniformis) nematodes. Objectives formulated at a coordinating meeting in 2003 that included participants from public institutions and p...

  12. HOST RESISTANCE TO TRICHINELLA SPIRALIS INFECTION IN MICE AND RATS: SPECIES-DEPENDENT EFFECTS OF CYCLOPHOSPHAMIDE EXPOSURE

    EPA Science Inventory

    Host resistance to Trichinella spiralis infection was compared in rats (F344) and mice (C57BL/6J) following various cyclophosphamide (CY) treatment schedules. Dozes of CY given to mice were adjusted by body surface area to be comparable to rat doses. dult parasite elimination was...

  13. Host plant resistance to megacopta cribraria (Hemiptera: Plataspidae) in diverse soybean germplasm maturity groups V through VIII

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Initially discovered in Georgia in 2009, the exotic invasive plataspid, Megacopta cribraria Fabricius has become a serious pest of soybean. Managing M. cribraria in soybean typically involves the application of broad-spectrum insecticides. Soybean host plant resistance is an attractive alternative...

  14. Corrosion resistant positive electrode for high-temperature, secondary electrochemical cell

    DOEpatents

    Otto, Neil C.; Warner, Barry T.; Smaga, John A.; Battles, James E.

    1983-01-01

    The corrosion rate of low carbon steel within a positive electrode of a high-temperature, secondary electrochemical cell that includes FeS as active material is substantially reduced by incorporating therein finely divided iron powder in stoichiometric excess to the amount required to form FeS in the fully charged electrode. The cell typically includes an alkali metal or alkaline earth metal as negative electrode active material and a molten metal halide salt as electrolyte. The excess iron permits use of inexpensive carbon steel alloys that are substantially free of the costly corrosion resistant elements chromium, nickel and molybdenum while avoiding shorten cell life resulting from high corrosion rates.

  15. Corrosion resistant positive electrode for high-temperature, secondary electrochemical cell

    DOEpatents

    Otto, N.C.; Warner, B.T.; Smaga, J.A.; Battles, J.E.

    1982-07-07

    The corrosion rate of low carbon steel within a positive electrode of a high-temperature, secondary electrochemical cell that includes FeS as active material is substantially reduced by incorporating therein finely divided iron powder in stoichiometric excess to the amount required to form FeS in the fully charged electrode. The cell typically includes an alkali metal or alkaline earth metal as negative electrode active material and a molten metal halide salt as electrolyte. The excess iron permits use of inexpensive carbon steel alloys that are substantially free of the costly corrosion resistant elements chromium, nickel and molybdenum while avoiding shorten cell life resulting from high corrosion rates.

  16. Host Resistance to Intracellular Infection: Mutation of Natural Resistance-associated Macrophage Protein 1 (Nramp1) Impairs Phagosomal Acidification

    PubMed Central

    Hackam, David J.; Rotstein, Ori D.; Zhang, Wei-jian; Gruenheid, Samantha; Gros, Philippe; Grinstein, Sergio

    1998-01-01

    The mechanisms underlying the survival of intracellular parasites such as mycobacteria in host macrophages remain poorly understood. In mice, mutations at the Nramp1 gene (for natural resistance-associated macrophage protein), cause susceptibility to mycobacterial infections. Nramp1 encodes an integral membrane protein that is recruited to the phagosome membrane in infected macrophages. In this study, we used microfluorescence ratio imaging of macrophages from wild-type and Nramp1 mutant mice to analyze the effect of loss of Nramp1 function on the properties of phagosomes containing inert particles or live mycobacteria. The pH of phagosomes containing live Mycobacterium bovis was significantly more acidic in Nramp1- expressing macrophages than in mutant cells (pH 5.5 ± 0.06 versus pH 6.6 ± 0.05, respectively; P <0.005). The enhanced acidification could not be accounted for by differences in proton consumption during dismutation of superoxide, phagosomal buffering power, counterion conductance, or in the rate of proton “leak”, as these were found to be comparable in wild-type and Nramp1-deficient macrophages. Rather, after ingestion of live mycobacteria, Nramp1-expressing cells exhibited increased concanamycin-sensitive H+ pumping across the phagosomal membrane. This was associated with an enhanced ability of phagosomes to fuse with vacuolar-type ATPase–containing late endosomes and/or lysosomes. This effect was restricted to live M. bovis and was not seen in phagosomes containing dead M. bovis or latex beads. These data support the notion that Nramp1 affects intracellular mycobacterial replication by modulating phagosomal pH, suggesting that Nramp1 plays a central role in this process. PMID:9670047

  17. Enhancement of host resistance against Listeria infection by Lactobacillus casei: Role of macrophages

    SciTech Connect

    Sato, K.

    1984-05-01

    Among the 10 species of the genus Lactobacillus, L. casei showed the strongest protective action against Listeria monocytogenes infection in mice. The activity of L. casei differed with regard to the dose of administration. The anti-L. monocytogenes resistance in mice intravenously administered 5.5 X 10(7), 2.8 X 10(8), or 1.1 X 10(9) L. casei cells was most manifest at ca. 2, 2 and 13, and 3 to 21 days after its administration, respectively. The growth of L. monocytogenes in the liver of mice injected with L. casei (10(7), 10(8), or 10(9) cells) 48 h after infection was suppressed, particularly when 10(8) or 10(9) L. casei cells were given 2 or 13 days before the induced infection, respectively. This suppression of L. monocytogenes growth was overcome by carrageenan treatment or X-ray irradiation. (/sup 3/H)thymidine incorporation into the liver DNA increased 13 days after administration of L. casei, and augmentation of (/sup 3/H)thymidine incorporation during 6 to 48 h after infection was dependent on the dose of L. casei. Peritoneal macrophage accumulation observed 1 to 5 days after intraperitoneal injection of UV-killed L. monocytogenes was markedly enhanced when the mice were treated with L. casei cells 13 days before macrophage elicitation. Therefore, the enhanced host resistance by L. casei to L. monocytogenes infection may be mediated by macrophages migrating from the blood stream to the reticuloendothelial system in response to L. casei injection before or after L. monocytogenes infection.

  18. PR10 expression in maize and its effect on host resistance against Aspergillus flavus infection and aflatoxin production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize (Zea mays L.) is a major crop susceptible to Aspergillus flavus infection and subsequent contamination with aflatoxins, the potent carcinogenic secondary metabolites of the fungus. Protein profiles of maize genotypes resistant and susceptible to A. flavus infection and/or aflatoxin contaminati...

  19. Metagenomic Assembly Reveals Hosts of Antibiotic Resistance Genes and the Shared Resistome in Pig, Chicken, and Human Feces.

    PubMed

    Ma, Liping; Xia, Yu; Li, Bing; Yang, Ying; Li, Li-Guan; Tiedje, James M; Zhang, Tong

    2016-01-01

    The risk associated with antibiotic resistance disseminating from animal and human feces is an urgent public issue. In the present study, we sought to establish a pipeline for annotating antibiotic resistance genes (ARGs) based on metagenomic assembly to investigate ARGs and their co-occurrence with associated genetic elements. Genetic elements found on the assembled genomic fragments include mobile genetic elements (MGEs) and metal resistance genes (MRGs). We then explored the hosts of these resistance genes and the shared resistome of pig, chicken and human fecal samples. High levels of tetracycline, multidrug, erythromycin, and aminoglycoside resistance genes were discovered in these fecal samples. In particular, significantly high level of ARGs (7762 ×/Gb) was detected in adult chicken feces, indicating higher ARG contamination level than other fecal samples. Many ARGs arrangements (e.g., macA-macB and tetA-tetR) were discovered shared by chicken, pig and human feces. In addition, MGEs such as the aadA5-dfrA17-carrying class 1 integron were identified on an assembled scaffold of chicken feces, and are carried by human pathogens. Differential coverage binning analysis revealed significant ARG enrichment in adult chicken feces. A draft genome, annotated as multidrug resistant Escherichia coli, was retrieved from chicken feces metagenomes and was determined to carry diverse ARGs (multidrug, acriflavine, and macrolide). The present study demonstrates the determination of ARG hosts and the shared resistome from metagenomic data sets and successfully establishes the relationship between ARGs, hosts, and environments. This ARG annotation pipeline based on metagenomic assembly will help to bridge the knowledge gaps regarding ARG-associated genes and ARG hosts with metagenomic data sets. Moreover, this pipeline will facilitate the evaluation of environmental risks in the genetic context of ARGs. PMID:26650334

  20. Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition.

    PubMed

    Xiong, Haitao; Guo, Bingxiu; Gan, Zhenshun; Song, Deguang; Lu, Zeqing; Yi, Hongbo; Wu, Yueming; Wang, Yizhen; Du, Huahua

    2016-01-01

    Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days before E. coli O157:H7 challenge was designed to investigate porcine HDP expression, inflammation and E. coli O157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cells in vitro were examined. Butyrate treatment (i) alleviated the clinical symptoms of E. coli O157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced the E. coli O157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPs in vitro and in vivo via histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance of E. coli O157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition. PMID:27230284

  1. Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition

    PubMed Central

    Xiong, Haitao; Guo, Bingxiu; Gan, Zhenshun; Song, Deguang; Lu, Zeqing; Yi, Hongbo; Wu, Yueming; Wang, Yizhen; Du, Huahua

    2016-01-01

    Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days before E. coli O157:H7 challenge was designed to investigate porcine HDP expression, inflammation and E. coli O157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cells in vitro were examined. Butyrate treatment (i) alleviated the clinical symptoms of E. coli O157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced the E. coli O157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPs in vitro and in vivo via histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance of E. coli O157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition. PMID:27230284

  2. The effect of glucan--a host resistance activator--and ampicillin on experimental intraabdominal sepsis.

    PubMed

    Lahnborg, G; Hedström, K G; Nord, C E

    1982-11-01

    Glucan, a beta-1-3-polyglucosidic component of the cell wall of Saccharomyces cervisiae, was evaluated for its ability to influence the survival rate in rats with induced intraabdominal sepsis. To mimic closely the human bacteriological intestinal flora, the rats, in 4 groups each of 15 animals, were fed a lean meat diet. Intraabdominal sepsis was induced by resecting 1 cm of the intestine and reimplanting it in the abdominal cavity, reestablishing intestinal continuity by one-layer end-to-end anastomosis. The rats were injected with glucan, isovolumetric saline, and ampicillin or glucan plus ampicillin. The results indicate a significant decrease in mortality in the group treated with ampicillin compared with the group treated with saline only. The group treated with glucan plus ampicillin differed significantly from the group given ampicillin. The bacterial flora was not qualitatively influenced by glucan administration. It is concluded that glucan, in combination with ampicillin, has a significant effect on the survival rate of rats with induced peritonitis, probably by enhancing the activities of the reticuloendothelial system--an important part of the total host resistance. PMID:7161767

  3. Study on the thermal resistance in secondary particles chain of silica aerogel by molecular dynamics simulation

    SciTech Connect

    Liu, M.; Qiu, L. E-mail: jzzhengxinghua@163.com; Zheng, X. H. E-mail: jzzhengxinghua@163.com; Zhu, J.; Tang, D. W.

    2014-09-07

    In this article, molecular dynamics simulation was performed to study the heat transport in secondary particles chain of silica aerogel. The two adjacent particles as the basic heat transport unit were modelled to characterize the heat transfer through the calculation of thermal resistance and vibrational density of states (VDOS). The total thermal resistance of two contact particles was predicted by non-equilibrium molecular dynamics simulations (NEMD). The defects were formed by deleting atoms in the system randomly first and performing heating and quenching process afterwards to achieve the DLCA (diffusive limited cluster-cluster aggregation) process. This kind of treatment showed a very reasonable prediction of thermal conductivity for the silica aerogels compared with the experimental values. The heat transport was great suppressed as the contact length increased or defect concentration increased. The constrain effect of heat transport was much significant when contact length fraction was in the small range (<0.5) or the defect concentration is in the high range (>0.5). Also, as the contact length increased, the role of joint thermal resistance played in the constraint of heat transport was increasing. However, the defect concentration did not affect the share of joint thermal resistance as the contact length did. VDOS of the system was calculated by numerical method to characterize the heat transport from atomic vibration view. The smaller contact length and greater defect concentration primarily affected the longitudinal acoustic modes, which ultimately influenced the heat transport between the adjacent particles.

  4. Improved secondary caries resistance via augmented pressure displacement of antibacterial adhesive

    PubMed Central

    Zhou, Wei; Niu, Li-na; Huang, Li; Fang, Ming; Chang, Gang; Shen, Li-juan; Tay, Franklin R.; Chen, Ji-hua

    2016-01-01

    The present in vitro study evaluated the secondary caries resistance potential of acid-etched human coronal dentin bonded using augmented pressure adhesive displacement in conjunction with an experimental antibacterial adhesive. One hundred and twenty class I cavities were restored with a commercial non-antibacterial etch-and-rinse adhesive (N) or an experimental antibacterial adhesive (A) which was displaced by gentle air-blow (G) or augmented pressure air-blow (H). After bonding and restoration with resin composite, the resulted 4 groups (N-G, N-H, A-G and A-H) were exposed to Streptococcus mutans biofilm for 4, 8, 15, 20 or 25 days. The development of secondary caries in the bonding interface was then examined by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Data acquired from 15, 20 and 25 days of artificial caries induction were analyzed with three-way ANOVA at α = 0.05. The depth of the artificial carious lesions was significantly affected by “adhesive type” (Single Bond 2 vs experimental antibacterial adhesive p = 0.003), “intensity of adhesive displacement” (gentle vs augmented-pressure adhesive displacement; p < 0.001), as well as “artificial caries induction time” (p < 0.001). The combined use of augmented pressure adhesive displacement and experimental antibacterial adhesive reduces the progression of secondary caries. PMID:26928742

  5. Cotton Square Morphology Offers New Insights into Host Plant Resistance to Cotton Fleahopper (Hemiptera: Miridae) in Upland Cotton.

    PubMed

    McLoud, Laura Ann; Hague, Steven; Knutson, Allen; Wayne Smith, C; Brewer, Michael

    2016-02-01

    Cotton fleahopper, Pseudatomoscelis seriatus (Reuter) (Hemiptera: Miridae), is a piercing-sucking pest of cotton (Gossypium hirsutum L.) that feeds preferentially on developing flower buds, called squares. Heavy infestations cause yield reductions that result from abscission of squares damaged by the cotton fleahopper feeding. Antixenosis, or nonpreference, has been reported as a mechanism of host plant resistance in cotton to cotton fleahopper. Square structure, particularly the placement of the reproductive tissues, and stylet penetration were investigated as factors that influence resistance to cotton fleahopper in cotton lines derived from crosses with Pilose, a cultigen of upland cotton resistant to cotton fleahopper, and backcrossed with high-yielding, susceptible lines. Ovary depth varied among the lines tested and was found to be a heritable trait that affected the ability of a fleahopper's feeding stylets to penetrate the reproductive tissues in the square and might influence preference. Behavioral assays suggested antixenosis as a mechanism of host plant resistance, and the trait conferring antixenosis was found to be heritable. Results suggest ovary depth plays a role in conferring resistance to cotton fleahopper and is an exploitable trait in resistance breeding. PMID:26475922

  6. Toward elucidation of genetic and functional genetic mechanisms in corn host resistance to Aspergillus flavus infection and aflatoxin contamination

    PubMed Central

    Shan, Xueyan; Williams, W. Paul

    2014-01-01

    Aflatoxins are carcinogenic mycotoxins produced by some species in the Aspergillus genus, such as A. flavus and A. parasiticus. Contamination of aflatoxins in corn profusely happens at pre-harvest stage when heat and drought field conditions favor A. flavus colonization. Commercial corn hybrids are generally susceptible to A. flavus infection. An ideal strategy for preventing aflatoxin contamination is through the enhancement of corn host resistance to Aspergillus infection and aflatoxin production. Constant efforts have been made by corn breeders to develop resistant corn genotypes. Significantly low levels of aflatoxin accumulation have been determined in certain resistant corn inbred lines. A number of reports of quantitative trait loci have provided compelling evidence supporting the quantitative trait genetic basis of corn host resistance to aflatoxin accumulation. Important findings have also been obtained from the investigation on candidate resistance genes through transcriptomics approach. Elucidation of molecular mechanisms will provide in-depth understanding of the host–pathogen interactions and hence facilitate the breeding of corn with resistance to A. flavus infection and aflatoxin accumulation. PMID:25101068

  7. Learned parasite avoidance is driven by host personality and resistance to infection in a fish-trematode interaction.

    PubMed

    Klemme, Ines; Karvonen, Anssi

    2016-09-14

    Cognitive abilities related to the assessment of risk improve survival. While earlier studies have examined the ability of animals to learn to avoid predators, learned parasite avoidance has received little interest. In a series of behavioural trials with the trematode parasite Diplostomum pseudospathaceum, we asked whether sea trout (Salmo trutta trutta) hosts show associative learning in the context of parasitism and if so, whether learning capacity is related to the likelihood of infection mediated through host personality and resistance. We show that animals are capable of learning to avoid visual cues associated with the presence of parasites. However, avoidance behaviour ceased after the likely activation of host resistance following consecutive exposures during learning, suggesting that resistance to infection outweighs avoidance. Further, we found a positive relationship between learning ability and boldness, suggesting a compensation of risky lifestyles through increased investment in cognitive abilities. By contrast, an increased risk of infection due to low resistance was not balanced by learning ability. Instead, these traits were positively related, which may be explained by inherent physiological qualities controlling both traits. Overall, the results demonstrate that parasitism, in addition to other biological interactions such as predation, is an important selective factor in the evolution of animal cognition. PMID:27605504

  8. Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii.

    PubMed

    Oksanen, Anna; Aittomäki, Saara; Jankovic, Dragana; Ortutay, Zsuzsanna; Pulkkinen, Kati; Hämäläinen, Sanna; Rokka, Anne; Corthals, Garry L; Watford, Wendy T; Junttila, Ilkka; O'Shea, John J; Pesu, Marko

    2014-12-01

    The proprotein convertase subtilisin/kexin enzymes proteolytically convert immature proproteins into bioactive molecules, and thereby they serve as key regulators of cellular homeostasis. The archetype proprotein convertase subtilisin/kexin, FURIN, is a direct target gene of the IL-12/STAT4 pathway and it is upregulated in Th1 cells. We have previously demonstrated that FURIN expression in T cells critically regulates the maintenance of peripheral immune tolerance and the functional maturation of pro-TGF-β1 in vivo, but FURIN's role in cell-mediated immunity and Th polarization has remained elusive. In this article, we show that T cell-expressed FURIN is essential for host resistance against a prototypic Th1 pathogen, Toxoplasma gondii, and for the generation of pathogen-specific Th1 lymphocytes, including Th1-IL-10 cells. FURIN-deficient Th cells instead show elevated expression of IL-4R subunit α on cell surface, sensitized IL-4/STAT6 signaling, and a propensity to polarize toward the Th2 phenotype. By exploring FURIN-interacting proteins in Jurkat T cells with Strep-Tag purification and mass spectrometry, we further identify an association with a cytoskeleton modifying Ras-related C3 botulinum toxin substrate/dedicator of cytokinesis 2 protein complex and unravel that FURIN promotes F-actin polymerization, which has previously been shown to downregulate IL-4R subunit α cell surface expression and promote Th1 responses. In conclusion, our results demonstrate that in addition to peripheral immune tolerance, T cell-expressed FURIN is also a central regulator of cell-mediated immunity and Th1/2 cell balance. PMID:25355923

  9. Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii

    PubMed Central

    Oksanen, Anna; Aittomäki, Saara; Jankovic, Dragana; Ortutay, Zsuzsanna; Pulkkinen, Kati; Hämäläinen, Sanna; Rokka, Anne; Corthals, Garry L.; Watford, Wendy T.; Junttila, Ilkka; O’Shea, John J.; Pesu, Marko

    2014-01-01

    The proprotein convertase subtilisin/kexin (PCSK) enzymes proteolytically convert immature proproteins into bioactive molecules and thereby they serve as key regulators of cellular homeostasis. The archetype PCSK, FURIN is a direct target gene of the IL-12/STAT4 pathway and it is upregulated in T helper 1 type cells. We have previously demonstrated that FURIN expression in T cells critically regulates the maintenance of peripheral immune tolerance and the functional maturation of pro-TGFβ-1 in vivo, but FURIN’s role in cell-mediated immunity and Th polarization has remained elusive. Here, we show that T-cell-expressed FURIN is essential for host resistance against a prototypic Th1 pathogen, Toxoplasma gondii and for the generation of pathogen-specific Th1 lymphocytes, including Th1-IL-10 cells. FURIN-deficient Th cells instead show elevated expression of IL-4 receptor subunit alpha (IL-4Rα) on cell surface, sensitized IL-4/STAT6 signaling and a propensity to polarize towards the Th2 phenotype. By exploring FURIN-interacting proteins in Jurkat T cells with Strep-Tag purification and mass-spectrometry we further identify an association with a cytoskeleton modifying RAC/DOCK2 protein complex and unravel that FURIN promotes F-actin polymerization, which has previously been shown to down-regulate IL-4Rα cell surface expression and promote Th1 responses. In conclusion, our results demonstrate that in addition to peripheral immune tolerance, T-cell-expressed FURIN is also a central regulator of cell-mediated immunity and Th1/2 cell balance. PMID:25355923

  10. Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands

    PubMed Central

    Guo, Zhengyu; González, Jorge Francisco; Hernandez, Julia N.; McNeilly, Tom N.; Corripio-Miyar, Yolanda; Frew, David; Morrison, Tyler; Yu, Peng; Li, Robert W.

    2016-01-01

    Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10−4). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed. PMID:27197554

  11. Scaling up from greenhouse resistance to fitness in the field for a host of an emerging forest disease

    PubMed Central

    Hayden, Katherine J; Garbelotto, Matteo; Dodd, Richard; Wright, Jessica W

    2013-01-01

    Forest systems are increasingly threatened by emergent, exotic diseases, yet management strategies for forest trees may be hindered by long generation times and scant background knowledge. We tested whether nursery disease resistance and growth traits have predictive value for the conservation of Notholithocarpus densiflorus, the host most susceptible to sudden oak death. We established three experimental populations to assess nursery growth and resistance to Phytophthora ramorum, and correlations between nursery-derived breeding values with seedling survival in a field disease trial. Estimates of nursery traits’ heritability were low to moderate, with lowest estimates for resistance traits. Within the field trial, survival likelihood was increased in larger seedlings and decreased with the development of disease symptoms. The seed-parent family wide likelihood of survival was likewise correlated with family predictors for size and resistance to disease in 2nd year laboratory assays, though not resistance in 1st year leaf assays. We identified traits and seedling families with increased survivorship in planted tanoaks, and a framework to further identify seed parents favored for restoration. The additive genetic variation and seedling disease dynamics we describe hold promise to refine current disease models and expand the understanding of evolutionary dynamics of emergent infectious diseases in highly susceptible hosts. PMID:24062805

  12. Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands.

    PubMed

    Guo, Zhengyu; González, Jorge Francisco; Hernandez, Julia N; McNeilly, Tom N; Corripio-Miyar, Yolanda; Frew, David; Morrison, Tyler; Yu, Peng; Li, Robert W

    2016-01-01

    Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10(-4)). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed. PMID:27197554

  13. Non-Thermal Plasma Treatment Diminishes Fungal Viability and Up-Regulates Resistance Genes in a Plant Host

    PubMed Central

    Panngom, Kamonporn; Lee, Sang Hark; Park, Dae Hoon; Sim, Geon Bo; Kim, Yong Hee; Uhm, Han Sup; Park, Gyungsoon; Choi, Eun Ha

    2014-01-01

    Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation) while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar) plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR) genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance. PMID:24911947

  14. Interplay between Parasitism and Host Ontogenic Resistance in the Epidemiology of the Soil-Borne Plant Pathogen Rhizoctonia solani

    PubMed Central

    Delarue, Patrick; Morlière, Stéphanie; Montfort, Françoise; Hervé, Maxime R.; Poggi, Sylvain

    2014-01-01

    Spread of soil-borne fungal plant pathogens is mainly driven by the amount of resources the pathogen is able to capture and exploit should it behave either as a saprotroph or a parasite. Despite their importance in understanding the fungal spread in agricultural ecosystems, experimental data related to exploitation of infected host plants by the pathogen remain scarce. Using Rhizoctonia solani / Raphanus sativus as a model pathosystem, we have obtained evidence on the link between ontogenic resistance of a tuberizing host and (i) its susceptibility to the pathogen and (ii) after infection, the ability of the fungus to spread in soil. Based on a highly replicable experimental system, we first show that infection success strongly depends on the host phenological stage. The nature of the disease symptoms abruptly changes depending on whether infection occurred before or after host tuberization, switching from damping-off to necrosis respectively. Our investigations also demonstrate that fungal spread in soil still depends on the host phenological stage at the moment of infection. High, medium, or low spread occurred when infection was respectively before, during, or after the tuberization process. Implications for crop protection are discussed. PMID:25127238

  15. Interplay between parasitism and host ontogenic resistance in the epidemiology of the soil-borne plant pathogen Rhizoctonia solani.

    PubMed

    Simon, Thomas E; Le Cointe, Ronan; Delarue, Patrick; Morlière, Stéphanie; Montfort, Françoise; Hervé, Maxime R; Poggi, Sylvain

    2014-01-01

    Spread of soil-borne fungal plant pathogens is mainly driven by the amount of resources the pathogen is able to capture and exploit should it behave either as a saprotroph or a parasite. Despite their importance in understanding the fungal spread in agricultural ecosystems, experimental data related to exploitation of infected host plants by the pathogen remain scarce. Using Rhizoctonia solani / Raphanus sativus as a model pathosystem, we have obtained evidence on the link between ontogenic resistance of a tuberizing host and (i) its susceptibility to the pathogen and (ii) after infection, the ability of the fungus to spread in soil. Based on a highly replicable experimental system, we first show that infection success strongly depends on the host phenological stage. The nature of the disease symptoms abruptly changes depending on whether infection occurred before or after host tuberization, switching from damping-off to necrosis respectively. Our investigations also demonstrate that fungal spread in soil still depends on the host phenological stage at the moment of infection. High, medium, or low spread occurred when infection was respectively before, during, or after the tuberization process. Implications for crop protection are discussed. PMID:25127238

  16. Increased plant growth and copper uptake of host and non-host plants by metal-resistant and plant growth-promoting endophytic bacteria.

    PubMed

    Sun, Leni; Wang, Xiaohan; Li, Ya

    2016-05-01

    The effects of inoculation with two metal-resistant and plant growth-promoting endophytic bacteria (Burkholderia sp. GL12 and Bacillus megaterium JL35) were evaluated on the plant growth and Cu uptake in their host Elsholtzia splendens and non-host Brassica napus plants grown in natural Cu-contaminated soil. The two strains showed a high level of ACC deaminase activities. In pot experiments, inoculation with strain GL12 significantly increased root and above-ground tissue dry weights of both plants, consequently increasing the total Cu uptake of E. splendens and Brassica napus by 132% and 48.2% respectively. Inoculation with strain JL35 was found to significantly increase not only the biomass of B. napus, consequently increasing the total Cu uptake of B. napus by 31.3%, but Cu concentration of E. splendens for above-ground tissues by 318% and roots by 69.7%, consequently increasing the total Cu uptake of E. splendens by 223%. The two strains could colonize the rhizosphere soils and root interiors of both plants. Notably, strain JL35 could colonize the shoot tissues and significantly increase the translocation factors and bioaccumulation factors of E. splendens. These results suggested that Burkholderia sp. GL12 and B. megaterium JL35 were valuable bacterial resource which had the potential in improving the efficiency of Cu phytoextraction by E. splendens and B. napus in a natural Cu-contaminated soil. PMID:26587767

  17. Interplay between seven secondary metal uptake systems is required for full metal resistance of Cupriavidus metallidurans.

    PubMed

    Herzberg, M; Bauer, L; Kirsten, A; Nies, D H

    2016-03-01

    The beta-proteobacterium Cupriavidus metallidurans is able to grow in metal-contaminated environments due to having sophisticated metal efflux systems. Here, the contribution of all seven known secondary metal uptake systems (ZupT, PitA, CorA1, CorA2, CorA3, ZntB, HoxN) to metal resistance is characterized. In a strategic deletion approach, all ten double deletion mutants, a variety of triple and quadruple mutants, and from the Δ4 mutant (ΔzupT ΔcorA1 ΔcorA2 ΔcorA3) the mutants Δ5 (=Δ4 ΔpitA), Δ6 (=Δ4 ΔpitA ΔzntB), and finally Δ7 (ΔzupT ΔcorA1 ΔcorA2 ΔcorA3 ΔpitA ΔzntB ΔhoxN) were constructed. Metal resistance, metal content, and regulation of expression of these genes were characterized in these mutants. The ΔzupT single deletion strain exhibited an extended lag phase in Tris-buffered liquid mineral salts medium (TMM) compared to its parent strain AE104, indicating a decreased fitness level. Further deletions up to Δ6 did not influence growth in TMM without added metals but fitness of the Δ7 strain dropped to a lower level compared to Δ6, Δ5 and ΔzupT. The cells of the Δ7 multiple deletion strain still contained all essential metals, demonstrating that additional metal import systems must exist in C. metallidurans. PitA was an important contributor of metal:phosphate complexes to C. metallidurans. Up to Δ5 no evidence was found for increased expression of the transporter genes to recruit substitutes for the deleted importers. Only the hoxN-lacZ reporter gene fusion displayed a changed expression pattern in the Δ6 strain, indicating recruitment of HoxN. Metal resistance of the deletion strains decreased along the deletion series although all strains still contained metal efflux systems: up to the Δ6 mutant the overall fitness was kept at the ΔzupT mutant strain level at the cost of a diminished competence to handle μM concentrations of transition metals. Together, these data demonstrated an important contribution of the seven

  18. Cell Wall Biomolecular Composition Plays a Potential Role in the Host Type II Resistance to Fusarium Head Blight in Wheat.

    PubMed

    Lahlali, Rachid; Kumar, Saroj; Wang, Lipu; Forseille, Li; Sylvain, Nicole; Korbas, Malgorzata; Muir, David; Swerhone, George; Lawrence, John R; Fobert, Pierre R; Peng, Gary; Karunakaran, Chithra

    2016-01-01

    Fusarium head blight (FHB) is a serious disease of wheat worldwide. Cultivar resistance to FHB depends on biochemical factors that confine the pathogen spread in spikes. Breeding for cultivar resistance is considered the most practical way to manage this disease. In this study, different spectroscopy and microscopy techniques were applied to discriminate resistance in wheat genotypes against FHB. Synchrotron-based spectroscopy and imaging techniques, including focal plane array infrared and X-ray fluorescence (XRF) spectroscopy were used to understand changes in biochemical and nutrients in rachis following FHB infection. Sumai3 and Muchmore were used to represent resistant and susceptible cultivars to FHB, respectively, in this study. The histological comparison of rachis showed substantial differences in the cell wall thickness between the cultivars after infection. Synchrotron-based infrared imaging emphasized substantial difference in biochemical composition of rachis samples between the two cultivars prior to visible symptoms; in the resistant Sumai3, infrared bands representing lignin and hemicellulose were stronger and more persistent compared to the susceptible cultivar. These bands may be the candidates of biochemical markers for FHB resistance. Focal plane array infrared imaging (FPA) spectra from the rachis epidermis and vascular bundles revealed a new band (1710 cm(-1)) related to the oxidative stress on the susceptible cultivar only. XRF spectroscopy data revealed differences in nutrients composition between cultivars, and between controls and inoculated samples, with substantial increases observed for Ca, K, Mn, Fe, Zn, and Si in the resistant cultivar. These nutrients are related to cell wall stability, metabolic process, and plant defense mechanisms such as lignification pathway and callose deposition. The combination of cell wall composition and lignification plays a role in the mechanism of type II host resistance to FHB. Biochemical profiling

  19. Cell Wall Biomolecular Composition Plays a Potential Role in the Host Type II Resistance to Fusarium Head Blight in Wheat

    PubMed Central

    Lahlali, Rachid; Kumar, Saroj; Wang, Lipu; Forseille, Li; Sylvain, Nicole; Korbas, Malgorzata; Muir, David; Swerhone, George; Lawrence, John R.; Fobert, Pierre R.; Peng, Gary; Karunakaran, Chithra

    2016-01-01

    Fusarium head blight (FHB) is a serious disease of wheat worldwide. Cultivar resistance to FHB depends on biochemical factors that confine the pathogen spread in spikes. Breeding for cultivar resistance is considered the most practical way to manage this disease. In this study, different spectroscopy and microscopy techniques were applied to discriminate resistance in wheat genotypes against FHB. Synchrotron-based spectroscopy and imaging techniques, including focal plane array infrared and X-ray fluorescence (XRF) spectroscopy were used to understand changes in biochemical and nutrients in rachis following FHB infection. Sumai3 and Muchmore were used to represent resistant and susceptible cultivars to FHB, respectively, in this study. The histological comparison of rachis showed substantial differences in the cell wall thickness between the cultivars after infection. Synchrotron-based infrared imaging emphasized substantial difference in biochemical composition of rachis samples between the two cultivars prior to visible symptoms; in the resistant Sumai3, infrared bands representing lignin and hemicellulose were stronger and more persistent compared to the susceptible cultivar. These bands may be the candidates of biochemical markers for FHB resistance. Focal plane array infrared imaging (FPA) spectra from the rachis epidermis and vascular bundles revealed a new band (1710 cm−1) related to the oxidative stress on the susceptible cultivar only. XRF spectroscopy data revealed differences in nutrients composition between cultivars, and between controls and inoculated samples, with substantial increases observed for Ca, K, Mn, Fe, Zn, and Si in the resistant cultivar. These nutrients are related to cell wall stability, metabolic process, and plant defense mechanisms such as lignification pathway and callose deposition. The combination of cell wall composition and lignification plays a role in the mechanism of type II host resistance to FHB. Biochemical profiling

  20. Computational Analysis of HIV-1 Resistance Based on Gene Expression Profiles and the Virus-Host Interaction Network

    PubMed Central

    Huang, Tao; Xu, Zhongping; Chen, Lei; Cai, Yu-Dong; Kong, Xiangyin

    2011-01-01

    A very small proportion of people remain negative for HIV infection after repeated HIV-1 viral exposure, which is called HIV-1 resistance. Understanding the mechanism of HIV-1 resistance is important for the development of HIV-1 vaccines and Acquired Immune Deficiency Syndrome (AIDS) therapies. In this study, we analyzed the gene expression profiles of CD4+ T cells from HIV-1-resistant individuals and HIV-susceptible individuals. One hundred eighty-five discriminative HIV-1 resistance genes were identified using the Minimum Redundancy-Maximum Relevance (mRMR) and Incremental Feature Selection (IFS) methods. The virus protein target enrichment analysis of the 185 HIV-1 resistance genes suggested that the HIV-1 protein nef might play an important role in HIV-1 infection. Moreover, we identified 29 infection information exchanger genes from the 185 HIV-1 resistance genes based on a virus-host interaction network analysis. The infection information exchanger genes are located on the shortest paths between virus-targeted proteins and are important for the coordination of virus infection. These proteins may be useful targets for AIDS prevention or therapy, as intervention in these pathways could disrupt communication with virus-targeted proteins and HIV-1 infection. PMID:21394196

  1. Recessive resistance in Pisum sativum and potyvirus pathotype resolved in a gene-for-cistron correspondence between host and virus.

    PubMed

    Johansen, I E; Lund, O S; Hjulsager, C K; Laursen, J

    2001-07-01

    Pea seed-borne mosaic potyvirus (PSbMV) isolates are divided into pathotypes P-1, P-2, and P-4 according to their infection profile on a panel of Pisum sativum lines. P. sativum PI 269818 is resistant to P-1 and P-2 isolates and is susceptible to P-4 isolates. Resistance to P-1 is inherited as a single recessive gene, denoted sbm-1, and the pathogenicity determinant has previously been mapped to the virus-coded protein VPg. In the cultivar Bonneville, a second recessive gene, sbm-2, confers specific resistance to P-2. By exchanging cistrons between a P-2 and a P-4 isolate, the P3-6k1 cistron was identified as the PSbMV host-specific pathogenicity determinant on Bonneville. Exchange of P3-6k1 did not affect infection on PI 269818, and infection of Bonneville was not altered by substitution of the VPg cistron, indicating that P3-6k1 and VPg are independent determinants of pathotype-specific infectivity. On PI 269818 the pathogenicity determinant of both P-1 and P-2 mapped to the N terminus of VPg. This suggests that VPg from the P-1 and P-2 isolates are functionally similar on this host and that resistance to P-1 and P-2 in PI 269818 may operate by the same mechanism. Identification of VPg-sbm-1 and P3-6k1-sbm-2 as independent pairs of genetic interactors between PSbMV and P. sativum provides a simple explanation of the three known pathotypes of PSbMV. Furthermore, analysis of beta-glucuronidase-tagged P-2 virus indicated that sbm-2 resistance affected an early step in infection, implying that the P3-6k1 region plays a critical role in potyvirus replication or cell-to-cell movement. PMID:11413328

  2. Natural resistance-associated macrophage protein is a cellular receptor for sindbis virus in both insect and mammalian hosts.

    PubMed

    Rose, Patrick P; Hanna, Sheri L; Spiridigliozzi, Anna; Wannissorn, Nattha; Beiting, Daniel P; Ross, Susan R; Hardy, Richard W; Bambina, Shelly A; Heise, Mark T; Cherry, Sara

    2011-08-18

    Alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were nonpermissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multipass membrane proteins for infection. PMID:21843867

  3. The mode of host resistance to Plasmopara viticola infection of grapevines.

    PubMed

    Yu, Ying; Zhang, Yali; Yin, Ling; Lu, Jiang

    2012-11-01

    ABSTRACT The resistance and susceptibility of grapevines to downy mildew (DM) disease caused by Plasmopara viticola were compared among different cultivars/accessions belonging to Vitis vinifera, V. rotundifolia, and 10 oriental Vitis species. After inoculation with P. viticola pathogen, no symptom was found in V. rotundifolia grapevines at all, while oriental species V. davidii and V. piasezkii, like V. vinifera, were susceptible to DM disease. The other eight oriental Vitis species showed various resistance levels to DM disease. Intraspecific resistant variations were also observed in V. amurensis. Microscopy studies were conducted on various time courses after pathogen infection on grape leaves. P. viticola hyphae were not observed in V. rotundifolia cultivars, while symptoms with varying degrees of severity were observed among the Euvitis species. In general, the DM resistant oriental species showed a slower development of hypha and less formation of haustoria than DM susceptible V. vinifera grapevines. Cells with distinctive fluorescence were observed in V. rotundifolia and the oriental species V. pseudoreticulata, and callose deposits were observed in V. rotundifolia, V. pseudoreticulata, and V. amurensis grapevines. Based on the results of morphological observations and microscopy studies, we concluded that there were five levels of grapevine resistance to P. viticola pathogen: (i) immune, (ii) extremely resistant, (iii) resistant, (iv) partly resistant, and (v) susceptible. PMID:22877313

  4. Potential of host-plant resistance as an alternative control measure for sugarbeet root maggot

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugarbeet (Beta vulgaris L.) Germplasm lines with sugarbeet root maggot (Tetanops myopaeformis von Röder) (SBRM) resistance have been available since 1996. Two resistant germplasm lines, F1015 and F1016, and a susceptible germplasm line, F1010, crossed with three susceptible CMS lines (L53cms, FC50...

  5. Resistance to Plasmopara viticola in a grapevine segregating population is associated with stilbenoid accumulation and with specific host transcriptional responses

    PubMed Central

    2011-01-01

    the categories defense response, photosynthesis, primary and secondary metabolism, signal transduction and transport. Conclusions This study reports the results of a combined metabolic and transcriptional profiling of a grapevine population segregating for resistance to P. viticola. Some resistant individuals were identified and further characterized at the molecular level. These results will be valuable to future grapevine breeding programs. PMID:21838877

  6. Selection and Characterization of Phage-Resistant Mutant Strains of Listeria monocytogenes Reveal Host Genes Linked to Phage Adsorption

    PubMed Central

    Denes, Thomas; den Bakker, Henk C.; Tokman, Jeffrey I.; Guldimann, Claudia

    2015-01-01

    Listeria-infecting phages are readily isolated from Listeria-containing environments, yet little is known about the selective forces they exert on their host. Here, we identified that two virulent phages, LP-048 and LP-125, adsorb to the surface of Listeria monocytogenes strain 10403S through different mechanisms. We isolated and sequenced, using whole-genome sequencing, 69 spontaneous mutant strains of 10403S that were resistant to either one or both phages. Mutations from 56 phage-resistant mutant strains with only a single mutation mapped to 10 genes representing five loci on the 10403S chromosome. An additional 12 mutant strains showed two mutations, and one mutant strain showed three mutations. Two of the loci, containing seven of the genes, accumulated the majority (n = 64) of the mutations. A representative mutant strain for each of the 10 genes was shown to resist phage infection through mechanisms of adsorption inhibition. Complementation of mutant strains with the associated wild-type allele was able to rescue phage susceptibility for 6 out of the 10 representative mutant strains. Wheat germ agglutinin, which specifically binds to N-acetylglucosamine, bound to 10403S and mutant strains resistant to LP-048 but did not bind to mutant strains resistant to only LP-125. We conclude that mutant strains resistant to only LP-125 lack terminal N-acetylglucosamine in their wall teichoic acid (WTA), whereas mutant strains resistant to both phages have disruptive mutations in their rhamnose biosynthesis operon but still possess N-acetylglucosamine in their WTA. PMID:25888172

  7. Selection and Characterization of Phage-Resistant Mutant Strains of Listeria monocytogenes Reveal Host Genes Linked to Phage Adsorption.

    PubMed

    Denes, Thomas; den Bakker, Henk C; Tokman, Jeffrey I; Guldimann, Claudia; Wiedmann, Martin

    2015-07-01

    Listeria-infecting phages are readily isolated from Listeria-containing environments, yet little is known about the selective forces they exert on their host. Here, we identified that two virulent phages, LP-048 and LP-125, adsorb to the surface of Listeria monocytogenes strain 10403S through different mechanisms. We isolated and sequenced, using whole-genome sequencing, 69 spontaneous mutant strains of 10403S that were resistant to either one or both phages. Mutations from 56 phage-resistant mutant strains with only a single mutation mapped to 10 genes representing five loci on the 10403S chromosome. An additional 12 mutant strains showed two mutations, and one mutant strain showed three mutations. Two of the loci, containing seven of the genes, accumulated the majority (n = 64) of the mutations. A representative mutant strain for each of the 10 genes was shown to resist phage infection through mechanisms of adsorption inhibition. Complementation of mutant strains with the associated wild-type allele was able to rescue phage susceptibility for 6 out of the 10 representative mutant strains. Wheat germ agglutinin, which specifically binds to N-acetylglucosamine, bound to 10403S and mutant strains resistant to LP-048 but did not bind to mutant strains resistant to only LP-125. We conclude that mutant strains resistant to only LP-125 lack terminal N-acetylglucosamine in their wall teichoic acid (WTA), whereas mutant strains resistant to both phages have disruptive mutations in their rhamnose biosynthesis operon but still possess N-acetylglucosamine in their WTA. PMID:25888172

  8. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. I...

  9. Host resistance to phytophthora fruit rot in U.S. watermelon plant introductions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora capsici, distributed worldwide, is an aggressive pathogen with a broad host range, infecting solanaceous, leguminaceous, and cucurbitaceous crops. Phytophthora fruit rot of watermelon (Citrullus lanatus) caused by P. capsici was first reported in the U.S. in 1940. Since then, the dise...

  10. Host plant resistance in melon to sweetpotato whitefly in California and Arizona

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sweetpotato whitefly biotype B (MEAM1 cryptic species of Bemisia tabaci; SPWF) feeding severely impacts fall season melon (Cucumis melo L.) yield and quality in the lower deserts of California and Arizona. Melon accessions PI 313970 and TGR 1551 (PI 482420) have been reported to exhibit host plant r...

  11. Understanding mechanisms of host resistance against greenbug in cereal crops - an interdisciplinary, collaborative approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    At Texas AgriLife Research - Amarillo, we have an ongoing research program focusing on elucidating the mechanisms of interactions between the phloem-feeding aphid pests and cereal crop hosts using the wheat-greenbug as a model system. During this workshop, recent results from our research on the fo...

  12. Bacillus thuringiensis-toxin resistance management: Stable isotope assessment of alternate host use by Helicoverpa zea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data have been lacking on the proportion of H. zea larvae that develop on non-cotton host plants that can serve as a refuge from selection pressure for adaptation to Bt-cotton. We found that individual H. zea moths that develop as larvae on cotton and other plants with C3 physiology have a differen...

  13. UV light tolerance and reactivation potential of tetracycline-resistant bacteria from secondary effluents of a wastewater treatment plant.

    PubMed

    Huang, Jing-Jing; Xi, Jinying; Hu, Hong-Ying; Li, Yi; Lu, Sun-Qin; Tang, Fang; Pang, Yu-Chen

    2016-03-01

    Tetracycline-resistant bacteria (TRB) are of concern as emerging microbial contaminants in reclaimed water. To understand the effects of UV disinfection on TRB, both inactivation and reactivation profiles of TRB, as well as 16 tetracycline-resistant isolates from secondary effluent, were characterized in this study. The inactivation ratio of TRB was significantly lower (3.0-log) than that of heterotrophic bacteria (>4.0-log) in the secondary effluent. Additionally, the proportion of TRB significantly increased from 1.65% to 15.51% under 20mJ/cm(2) ultraviolet (UV) exposure. The inactivation rates of tetracycline-resistant isolates ranged from 0.57/s to 1.04/s, of which tetracycline-resistant Enterobacter-1 was the most tolerant to UV light. The reactivation of TRB, tetracycline-resistant isolated strains, as well as heterotrophic bacteria commonly occurred in the secondary effluent even after 20mJ/cm(2) UV exposure. The colony forming ability of TRB and heterotrophic bacteria reached 3.2-log and 3.0-log under 20mJ/cm(2) UV exposure after 22hr incubation. The final inactivation ratio of tetracycline-resistant Enterobacter-1 was 1.18-log under 20mJ/cm(2) UV exposure after 22hr incubation, which is similar to those of TRB (1.18-log) and heterotrophic bacteria (1.19-log). The increased proportion of TRB and the reactivation of tetracycline-resistant enterobacteria in reclaimed water could induce a microbial health risk during wastewater reuse. PMID:26969060

  14. Comparison of gene expression changes in susceptible, tolerant, and resistant hosts in response to infection with citrus tristeza virus and huanglongbing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogens Candidatus Liberibacter asiaticus (Las) and Citrus tristeza virus (CTV) are both phloem limited and have significant economic impact on citrus production wherever they are found. Studies of host resistance have indicated that Poncirus trifoliata has tolerance or resistance to both path...

  15. DNA repair in cells sensitive and resistant to cis-diamminedichloroplatinum(II): Host cell reactivation of damaged plasmid DNA

    SciTech Connect

    Sheibani, N.; Jennerwein, M.M.; Eastman, A. )

    1989-04-04

    cis-Diamminedichloroplatinum(II) (cis-DDP) has a broad clinical application as an effective anticancer drug. However, development of resistance to the cytotoxic effects is a limiting factor. In an attempt to understand the mechanism of resistance, the authors have employed a host cell reactivation assay of DNA repair using a cis-DDP-damaged plasmid vector. The efficiency of DNA repair was assayed by measuring the activity of an enzyme coded for by the plasmid vector. The plasmid expression vector pRSV cat contains the bacterial gene coding for chloramphenicol acetyltransferase (CAT) in a configuration which permits expression in mammalian cells. The plasmid was transfected into repair-proficient and -deficient Chinese hamster ovary cells, and CAT activity was subsequently measured in cell lysates. In the repair-deficient cells, one cis-DDP adduct per cat gene was sufficient to eliminate expression. An equivalent inhibition of CAT expression in the repair-proficient cells did not occur until about 8 times the amount of damage was introduced into the plasmid. These results implicate DNA intrastrand cross-links as the lesions responsible for the inhibition of CAT expression. This assay was used to investigate the potential role of DNA repair in mediating cis-DDP resistance in murine leukemia L1210 cells. The assay readily detects the presence or absence of repair and confirms that these resistant L1210 cells have an enhanced capacity for repair of cis-DDP-induced intrastrand cross-links.

  16. Introgression of an imidazolinone-resistance gene from winter wheat (Triticum aestivum L.) into jointed goatgrass (Aegilops cylindrica Host).

    PubMed

    Perez-Jones, Alejandro; Mallory-Smith, Carol A; Hansen, Jennifer L; Zemetra, Robert S

    2006-12-01

    Imidazolinone-resistant winter wheat (Triticum aestivum L.) is being commercialized in the USA. This technology allows wheat growers to selectively control jointed goatgrass (Aegilops cylindrica Host), a weed that is especially problematic because of its close genetic relationship with wheat. However, the potential movement of the imidazolinone-resistance gene from winter wheat to jointed goatgrass is a concern. Winter wheat and jointed goatgrass have the D genome in common and can hybridize and backcross under natural field conditions. Since the imidazolinone-resistance gene (Imi1) is located on the D genome, it is possible for resistance to be transferred to jointed goatgrass via hybridization and backcrossing. To study the potential for gene movement, BC(2)S(2) plants were produced artificially using imidazolinone-resistant winter wheat (cv. FS-4) as the female parent and a native jointed goatgrass collection as the male recurrent parent. FS-4, the jointed goatgrass collection, and 18 randomly selected BC(2)S(2) populations were treated with imazamox. The percentage of survival was 100% for the FS-4, 0% for the jointed goatgrass collection and 6 BC(2)S(2) populations, 40% or less for 2 BC(2)S(2) populations, and 50% or greater for the remaining 10 BC(2)S(2) populations. Chromosome counts in BC(2)S(3) plants showed a restoration of the chromosome number of jointed goatgrass, with four out of four plants examined having 28 chromosomes. Sequencing of AHASL1D in BC(2)S(3) plants derived from BC(2)S(2)-6 revealed the sexual transmission of Imi1 from FS-4 to jointed goatgrass. Imi1 conferred resistance to the imidazolinone herbicide imazamox, as shown by the in vitro assay for acetohydroxyacid synthase (AHAS) activity. PMID:17058103

  17. Androgen Deprivation Therapy and Secondary Hormone Therapy in the Management of Hormone-sensitive and Castration-resistant Prostate Cancer.

    PubMed

    Saad, Fred; Fizazi, Karim

    2015-11-01

    Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer (mPC). However, nearly all patients with mPC progress to castration-resistant PC (CRPC). Arrays of treatments, including secondary hormonal therapies, are available for the treatment of mPC and CRPC, which show efficacy when administered with ADT. Continuation of ADT is recommended for CRPC treatment as therapies are added. New secondary hormonal therapies include abiraterone, targeting the CYP17 enzyme family, and enzalutamide, an androgen receptor inhibitor with heightened binding specificity. The optimal decision-making process for CRPC treatment option remains unclear, pending further research and experience. PMID:26282624

  18. The Vibrio cholerae Mrp System: Cation/Proton Antiport Properties and Enhancement of Bile Salt Resistance in a Heterologous Host

    PubMed Central

    Dzioba-Winogrodzki, Judith; Winogrodzki, Olga; Krulwich, Terry A.; Boin, Markus A.; Häse, Claudia C.; Dibrov, Pavel

    2009-01-01

    The mrp operon from Vibrio cholerae encoding a putative multisubunit Na+/H+ antiporter was cloned and functionally expressed in the antiporter-deficient strain of Escherichia coli EP432. Cells of EP432 expressing Vc-Mrp exhibited resistance to Na+ and Li+ as well as to natural bile salts such as sodium cholate and taurocholate. When assayed in everted membrane vesicles of the E. coli EP432 host, Vc-Mrp had sufficiently high antiport activity to facilitate the first extensive analysis of Mrp system from a Gram-negative bacterium encoded by a group 2 mrp operon. Vc-Mrp was found to exchange protons for Li+, Na+, and K+ ions in pH-dependent manner with maximal activity at pH 9.0–9.5. Exchange was electrogenic (more than one H+ translocated per cation moved in opposite direction). The apparent Km at pH 9.0 was 1.08, 1.30, and 68.5 mM for Li+, Na+, and K+, respectively. Kinetic analyses suggested that Vc-Mrp operates in a binding exchange mode with all cations and protons competing for binding to the antiporter. The robust ion antiport activity of Vc-Mrp in sub-bacterial vesicles and its effect on bile resistance of the heterologous host make Vc-Mrp an attractive experimental model for the further studies of biochemistry and physiology of Mrp systems. PMID:18311075

  19. Regulatory Variation in HIV-1 Dependency Factor ZNRD1 Associates with Host Resistance to HIV-1 Acquisition

    PubMed Central

    An, Ping; Goedert, James J.; Donfield, Sharyne; Buchbinder, Susan; Kirk, Gregory D.; Detels, Roger; Winkler, Cheryl A.

    2014-01-01

    Background. ZNRD1 was identified as a host protein required for the completion of the human immunodeficiency virus (HIV) lifecycle in a genome-wide screen using small interfering RNA gene silencing. Subsequently, a genome-wide association study (GWAS) of host determinants for HIV-1 disease identified an association of single nucleotide polymorphisms (SNPs) in the ZNRD1 region with CD4+ T-cell depletion. Methods. We investigated the effects of SNPs in the ZNRD1 region on human immunodeficiency virus type 1 (HIV-1) infection and progression to clinical outcomes in 5 US-based HIV-1 longitudinal cohorts consisting of men who have sex with men, males with hemophilia, and injection drug users (IDUs) (n = 1865). SNP function was evaluated by electrophoretic mobility shift assay and promoter luciferase assay. Results. A haplotype in the ZNRD1 gene showed significant association with a 35% decreased risk of HIV-1 acquisition (OR = 0.65, 95% CI, .47–.89), independent of HLA-C rs9264942, in European Americans. The SNP rs3132130 tagging this haplotype, located in the ZNRD1 5′ upstream region, caused a loss of nuclear factor binding and decrease in ZNRD1 promoter activity. ZNRD1 variants also affected HIV-1 disease progression in European- and African-American cohorts. Conclusions. This study provides novel evidence that ZNRD1 polymorphism may confer host resistance to HIV-1 acquisition. PMID:24842830

  20. Competing pathways control host resistance to virus via tRNA modification and programmed ribosomal frameshifting.

    PubMed

    Maynard, Nathaniel D; Macklin, Derek N; Kirkegaard, Karla; Covert, Markus W

    2012-01-01

    Viral infection depends on a complex interplay between host and viral factors. Here, we link host susceptibility to viral infection to a network encompassing sulfur metabolism, tRNA modification, competitive binding, and programmed ribosomal frameshifting (PRF). We first demonstrate that the iron-sulfur cluster biosynthesis pathway in Escherichia coli exerts a protective effect during lambda phage infection, while a tRNA thiolation pathway enhances viral infection. We show that tRNA(Lys) uridine 34 modification inhibits PRF to influence the ratio of lambda phage proteins gpG and gpGT. Computational modeling and experiments suggest that the role of the iron-sulfur cluster biosynthesis pathway in infection is indirect, via competitive binding of the shared sulfur donor IscS. Based on the universality of many key components of this network, in both the host and the virus, we anticipate that these findings may have broad relevance to understanding other infections, including viral infection of humans. PMID:22294093

  1. Resistance and Susceptibility to Malarial Infection: A Host Defense Strategy against Malaria

    PubMed Central

    BAKIR, Hanaa; YONES, Doaa; GALAL, Lamia; HUSEEIN, Enas

    2015-01-01

    Background: In an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence. Methods: Two groups of mice from different genotypes were used (C57BL/6 (B6) and DBA/2 mice). The mice were infected with a virulent parasite line Plasmodium yoelii 17XL (P. yoelii 17XL). Parasitemia, hematocrit value and lymphocytes yielded by livers and spleens were evaluated. Fluorescence Activated Cell Sorting (FACS) analysis illustrated phenotypic characterization of lymphocytes. Results: Infection with P. yoelii 17XL did not result in the death of DBA/2 mice. In contrast, B6 mice developed significantly high parasitemia and succumbed to death. Using (FACS) analysis, DBA/2 mice were found to experience a marked expansion of interleukin (IL)-2Rβ+ CD3int cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 mice. Conclusion: The outcome of murine malaria infections depends on the dynamic interplay between the immune-mediator and the genotype of the host. PMID:26811732

  2. Temporal Effects of a Begomovirus Infection and Host Plant Resistance on the Preference and Development of an Insect Vector, Bemisia tabaci, and Implications for Epidemics

    PubMed Central

    Legarrea, Saioa; Barman, Apurba; Marchant, Wendy; Diffie, Stan; Srinivasan, Rajagopalbabu

    2015-01-01

    Persistent plant viruses, by altering phenotypic and physiological traits of their hosts, could modulate the host preference and fitness of hemipteran vectors. A majority of such modulations increase vector preference for virus-infected plants and improve vector fitness, ultimately favouring virus spread. Nevertheless, it remains unclear how these virus-induced modulations on vectors vary temporally, and whether host resistance to the pathogen influences such effects. This study addressed the two questions using a Begomovirus-whitefly-tomato model pathosystem. Tomato yellow leaf curl virus (TYLCV) -susceptible and TYLCV-resistant tomato genotypes were evaluated by whitefly-mediated transmission assays. Quantitative PCR revealed that virus accumulation decreased after an initial spike in all genotypes. TYLCV accumulation was less in resistant than in susceptible genotypes at 3, 6, and 12 weeks post inoculation (WPI). TYLCV acquisition by whiteflies over time from resistant and susceptible genotypes was also consistent with virus accumulation in the host plant. Furthermore, preference assays indicated that non-viruliferous whiteflies preferred virus-infected plants, whereas viruliferous whiteflies preferred non-infected plants. However, this effect was prominent only with the susceptible genotype at 6 WPI. The development of whiteflies on non-infected susceptible and resistant genotypes was not significantly different. However, developmental time was reduced when a susceptible genotype was infected with TYLCV. Together, these results suggest that vector preference and development could be affected by the timing of infection and by host resistance. These effects could play a crucial role in TYLCV epidemics. PMID:26529402

  3. Experimental elimination of parasites in nature leads to the evolution of increased resistance in hosts

    PubMed Central

    Dargent, Felipe; Scott, Marilyn E.; Hendry, Andrew P.; Fussmann, Gregor F.

    2013-01-01

    A reduction in the strength of selection is expected to cause the evolution of reduced trait expression. Elimination of a parasite should thus cause the evolution of reduced resistance to that parasite. To test this prediction in nature, we studied the fourth- and eighth-generation descendants of guppies (Poecilia reticulata) introduced into four natural streams following experimental elimination of a common and deleterious parasite (Gyrodactylus spp.). After two generations of laboratory rearing to control for plasticity and maternal effects, we infected individual fish to assess their resistance to the parasite. Contrary to theoretical expectations, the introduced guppy populations had rapidly and repeatably evolved increased resistance to the now-absent parasite. This evolution was not owing to a resistance-tolerance trade-off, nor to differences in productivity among the sites. Instead, a leading candidate hypothesis is that the rapid life-history evolution typical in such introductions pleiotropically increases parasite resistance. Our study adds a new dimension to the growing evidence for contemporary evolution in the wild, and also points to the need for a re-consideration of simple expectations from host–parasite theory. In particular, our results highlight the need for increased consideration of multiple sources of selection and pleiotropy when studying evolution in natural contexts. PMID:24197417

  4. Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors

    PubMed Central

    Zhang, Peisheng; Chen, Lei; Baird, Jason R.; Demidenko, Eugene; Turk, Mary Jo; Hoopes, P. Jack; Conejo-Garcia, Jose R.; Fiering, Steven

    2014-01-01

    Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic filed (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 minutes activated dendritic cells (DCs) and subsequently CD8+ T cells in the draining lymph node (dLN) and conferred resistance against rechallenge with B16 (but not unrelated Lewis Lung carcinoma) given 7 days post hyperthermia on both the primary tumor side and the contralateral side in a CD8+ T cell-dependent manner. Mice with heated primary tumors also resisted rechallenge given 30 days post hyperthermia. Mice with larger heated primary tumors had greater resistance to secondary tumors. No rechallenge resistance occurred when tumors were heated at 45°C. Our results demonstrate the promising potential of local hyperthermia treatment applied to identified tumors in inducing anti-tumor immune responses that reduce the risk of recurrence and metastasis. PMID:24566274

  5. A Multiple Decrement Life Table Reveals That Host Plant Resistance and Parasitism Are Major Causes of Mortality for the Wheat Stem Sawfly.

    PubMed

    Buteler, Micaela; Peterson, Robert K D; Hofland, Megan L; Weaver, David K

    2015-12-01

    This study investigated the dynamics of parasitism, host plant resistance, pathogens, and predation on the demography of wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), developing in susceptible (hollow stem) and resistant (solid stem) wheat hosts. This study is also the first to investigate the prevalence and impact of cannibalism on wheat stem sawfly mortality. Wheat stem sawflies were sampled in two commercial wheat fields over 4 yr from the egg stage through adult emergence, and multiple decrement life tables were constructed and analyzed. Cannibalism, host plant resistance, or unknown factors were the most prevalent factors causing egg mortality. Summer mortality of prediapause larvae ranged from 28 to 84%, mainly due to parasitism by Bracon cephi (Gahan) and Bracon lissogaster Muesebeck, cannibalism, and host plant resistance. Winter mortality ranged from 6 to 54% of the overwintering larvae, mainly due to unknown factors or pathogens. Cannibalism is a major cause of irreplaceable mortality because it is absolute, with only a single survivor in every multiple infested stem. Subsequent to obligate cannibalism, mortality of feeding larvae due to host plant resistance was lower in hollow stem wheat than in solid stem wheat. Mortality from host plant resistance was largely irreplaceable. Irreplaceable mortality due to parasitoids was greater in hollow stem wheat than in solid stem wheat. Host plant resistance due to stem solidness and parasitism in hollow stems cause substantial mortality in populations of actively feeding larvae responsible for all crop losses. Therefore, enhancing these mortality factors is vital to effective integrated pest management of wheat stem sawfly. PMID:26314030

  6. 22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... facet of U.S. culture at his or her discretion. How did you learn about being a host family? References: ... functioning business? (e.g., daycare, farm) g. Description of each household member (e.g., level of education... meals and transportation to and from school activities” b. Describe if anyone residing in the...

  7. Host Presidents' Address: A Discussion on Ways Catholic Higher Education Institutions Can Assist Catholic Elementary and Secondary Schools

    ERIC Educational Resources Information Center

    Leahy, William P.; McShane, Joseph M.

    2011-01-01

    As part of the third Catholic Higher Education Collaborative Conference (CHEC), an event cosponsored by Boston College and Fordham University, the host university presidents, Rev. William P. Leahy, S. J., and Rev. Joseph M. McShane, S. J., addressed conference attendees and discussed ways higher education institutions can assist Catholic…

  8. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice.

    PubMed

    Deshmukh, Hitesh S; Liu, Yuhong; Menkiti, Ogechukwu R; Mei, Junjie; Dai, Ning; O'Leary, Claire E; Oliver, Paula M; Kolls, Jay K; Weiser, Jeffrey N; Worthen, G Scott

    2014-05-01

    Neonatal colonization by microbes, which begins immediately after birth, is influenced by gestational age and the mother's microbiota and is modified by exposure to antibiotics. In neonates, prolonged duration of antibiotic therapy is associated with increased risk of late-onset sepsis (LOS), a disorder controlled by neutrophils. A role for the microbiota in regulating neutrophil development and susceptibility to sepsis in the neonate remains unclear. We exposed pregnant mouse dams to antibiotics in drinking water to limit transfer of maternal microbes to the neonates. Antibiotic exposure of dams decreased the total number and composition of microbes in the intestine of the neonates. This was associated with decreased numbers of circulating and bone marrow neutrophils and granulocyte/macrophage-restricted progenitor cells in the bone marrow of antibiotic-treated and germ-free neonates. Antibiotic exposure of dams reduced the number of interleukin-17 (IL-17)-producing cells in the intestine and production of granulocyte colony-stimulating factor (G-CSF). Granulocytopenia was associated with impaired host defense and increased susceptibility to Escherichia coli K1 and Klebsiella pneumoniae sepsis in antibiotic-treated neonates, which could be partially reversed by administration of G-CSF. Transfer of a normal microbiota into antibiotic-treated neonates induced IL-17 production by group 3 innate lymphoid cells (ILCs) in the intestine, increasing plasma G-CSF levels and neutrophil numbers in a Toll-like receptor 4 (TLR4)- and myeloid differentiation factor 88 (MyD88)-dependent manner and restored IL-17-dependent resistance to sepsis. Specific depletion of ILCs prevented IL-17- and G-CSF-dependent granulocytosis and resistance to sepsis. These data support a role for the intestinal microbiota in regulation of granulocytosis, neutrophil homeostasis and host resistance to sepsis in neonates. PMID:24747744

  9. Host-derived probiotics Enterococcus casseliflavus improves resistance against Streptococcus iniae infection in rainbow trout (Oncorhynchus mykiss) via immunomodulation.

    PubMed

    Safari, Reza; Adel, Milad; Lazado, Carlo C; Caipang, Christopher Marlowe A; Dadar, Maryam

    2016-05-01

    The present study evaluated the benefits of dietary administration of host-derived candidate probiotics Enterococcus casseliflavus in juvenile rainbow trout Oncorhynchus mykiss. Experimental diets were prepared by incorporating the microorganisms in the basal feed at 3 inclusion levels (i.e. 10(7) CFU g(-1) of feed [T1], 10(8) CFU g(-1) of feed [T2], 10(9) CFU g(-1) of feed [T3]). The probiotic feeds were administered for 8 weeks, with a group fed with the basal diet serving as control. The effects on growth performance, gut health, innate immunity and disease resistance were evaluated. Results showed that growth performance parameters were significantly improved in T2 and T3 groups. Activities of digestive enzymes such as trypsin and lipase were significantly higher in these two groups as well. Gut micro-ecology was influenced by probiotic feeding as shown by the significant increase in intestinal lactic acid bacteria and total viable aerobic counts in T2 and T3. Humoral immunity was impacted by dietary probiotics as total serum protein and albumin were significantly elevated in T3. The levels of serum IgM significantly increased in all probiotic fed groups at week 8; with the T3 group registering the highest increment. Respiratory burst activity of blood leukocytes were significantly improved in T2 and T3. Hematological profiling further revealed that neutrophil counts significantly increased in all probiotic fed groups. Challenge test showed that probiotic feeding significantly improved host resistance to Streptococcus iniae infection, specifically in T2 and T3 where a considerable modulation of immune responses was observed. Taken together, this study demonstrated E. casseliflavus as a potential probiotics for rainbow trout with the capability of improving growth performance and enhancing disease resistance by immunomodulation. PMID:26997202

  10. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    PubMed

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection. PMID:27114544

  11. Host resistance to pear psylla of breeding program selections and cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Twenty-one pear cultivars and breeders’ selections with interspecific pedigrees involving Pyrus ussuriensis Max. or P. pyrifolia (Burm.) Nakai crossed with P. communis were assessed to resistance pear psylla (Cacopsylla pyricola Förster) using a nymphal feeding antixenosis assay. The proportion of ...

  12. Host Plant Resistance to Green Peach Aphid, Myzus persicae (Sulzar), by Some Wild Types of Watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The green peach aphid, Myzus persicae (Sulzar), is an important pest of many vegetable crops. It damages crops by feeding and vectoring viruses. Potential sources of plant resistance against M. persicae were examined for watermelon. A multiple choice experiment was conducted with leaves of six wi...

  13. PULMONARY HOST DEFENSES AND RESISTANCE TO INFECTION FOLLOWING SUBCHRONIC EXPOSURE TO PHOSGENE

    EPA Science Inventory

    Acute exposure to phosgene, a toxic gas widely used in industrial processes, decreases resistance to bacteria in mice and rats and enhances susceptibility to B16 tumor cell challenge in mice. hese effects appear to be due to impaired alveolar macrophage and natural killer (NK) ce...

  14. EFFECTS OF ACUTE EXPOSURE TO PHOSGENE ON PULMONARY HOST DEFENSES AND RESISTANCE TO INFECTION

    EPA Science Inventory

    Phosgene is a toxic gas widely used in industrial processes. he most sensitive endpoint for phosgene toxicity in mice is decreased resistance to challenge with bacterial infection or tumor cells. were attributed to impaired alveolar macrophage (AM) and pulmonary natural killer ce...

  15. Suppression of bacterial blight on mustard greens with host plant resistance and Acibenzolar-S-Methyl

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial blight, caused by Pseudomonas cannabina pv. alisalensis, attacks the leaves of most brassica vegetables, including mustard greens (Brassica juncea). ‘Carolina Broadleaf,’ a new mustard cultivar, is resistant to bacterial blight. Acibenzolar-S-methyl (trade name Actigard) has been used to m...

  16. Interaction of sugarbeet host resistance and Rhizoctonia solani AG-2-2 IIIB strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Rhizoctonia root rot caused by Rhizoctonia solani can cause serious economic losses in sugarbeet fields. Preliminary evidence suggests there could be interactions between different strains and resistance sources. Thus, field studies were conducted to determine if nine R. solani AG-2-2 IIIB str...

  17. Pursuing Post-Secondary Education in the Host Country and the Occupational Attainment of Highly Educated Immigrants to Canada

    ERIC Educational Resources Information Center

    Adamuti-Trache, Maria

    2016-01-01

    This paper examines the occupational attainment of highly educated adult immigrants by employing a secondary analysis of three waves of the Longitudinal Survey of Immigrants to Canada that provide data on immigrant arrivals in 2000-2001. Occupational attainment is described in terms of matching immigrants' pre-migration occupation with the main…

  18. 22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... three (3) square meals daily? High School Information: a. Name and address of school (private or public...) participate(s) in at the school i. Does any member of your household work for the high school in a coaching... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Information To Be Collected on Secondary...

  19. 22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... three (3) square meals daily? High School Information: a. Name and address of school (private or public...) participate(s) in at the school i. Does any member of your household work for the high school in a coaching... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Information To Be Collected on Secondary...

  20. Geography and genealogy of the human host harbouring a distinctive drug-resistant strain of tuberculosis.

    PubMed

    Brassard, Paul; Henry, Kevin A; Schwartzman, Kevin; Jomphe, Michèle; Olson, Sherry H

    2008-05-01

    For a strain of Mycobacterium tuberculosis mono-resistant to pyrazinamide (PZA), we report the geographic distribution within Quebec of the 77 cases diagnosed during 1990-2000. Known as the Quebec mutation (or the pncA deletion), the strain is rare in urban areas and showed an unexpected concentration in Mauricie, one of the 16 health districts of the province, with a cluster of 10 cases situated in a rural area of 35-km radius. The cases occurred among people >50 (98%), of French Canadian origins (90%), and are understood to have arisen by reactivation. The rarity in Montreal and smaller cities is explained by the youthfulness of massive postwar migrations. To reach back into the history of settlement, we examined genealogies: 92,429 ancestral marriages for 32 of the 77 PZA-resistant isolates and 226,535 for a set of 85 controls with isolates of more diverse mycobacterial strains. Genealogical analysis showed no salient common ancestor for the cases, and kinship among them was no greater than observed in control samples from the same regions. But it identified an unsuspected geographical region as the site of ancestral concentrations prior to 1840, for both resistant strains and controls. The following scenario is proposed for the resistant strain: endemic in a specific geographical region by 1800, it dispersed with families moving into regions opened to settlement in the 1840s and 1850s, among them Mauricie, where dispersion was intensified by seasonal mobility of labour in logging, milling and marketing timber. In high-incidence areas, it is difficult to distinguish cases of reactivation from recent infections, but the low-incidence context allows us to observe a 200-year trajectory of a distinctive drug-resistant strain of M. tuberculosis. PMID:18316250

  1. Invasion of Ceratomyxa shasta (Myxozoa) and comparison of migration to the intestine between susceptible and resistant fish hosts.

    PubMed

    Bjork, Sarah J; Bartholomew, Jerri L

    2010-08-01

    The myxozoan parasite Ceratomyxa shasta infects salmonids causing ceratomyxosis, a disease elicited by proliferation of the parasite in the intestine. This parasite is endemic to the Pacific Northwest of North America and salmon and trout strains from endemic river basins show increased resistance to the parasite. It has been suggested that these resistant fish (i) exclude the parasite at the site of invasion and/or (ii) prevent establishment in the intestine. Using parasites pre-labeled with a fluorescent stain, carboxyfluorescein succinimidyl diacetate (CFSE), the gills were identified as the site of attachment of C. shasta in a susceptible fish strain. In situ hybridization (ISH) of histological sections was then used to describe the invasion of the parasites in the gill filaments. To investigate differences in the progress of infection between resistant and susceptible fish, a C. shasta-susceptible strain of rainbow trout (Oncorhynchus mykiss) and a C. shasta-resistant strain of Chinook salmon (Oncorhynchus tshawytscha) were sampled at consecutive time points following exposure at an endemic site. Using ISH in both species, the parasite was observed to migrate from the gill epithelium into the gill blood vessels where replication and release of parasite stages occurred. Quantitative PCR verified entry of the parasite into the blood. Parasite levels in blood increased 4days p.i. and remained at a consistent level until the second week when parasite abundance increased further and coincided with host mortality. The timing of parasite replication and migration to the intestine were similar for both fish species. The field exposure dose was unexpectedly high and apparently overwhelmed the Chinook salmon's defenses, as no evidence of resistance to parasite penetration into the gills or prevention of parasite establishment in the intestine was observed. PMID:20385137

  2. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    PubMed Central

    Hu, Zongli; Parekh, Urvi; Maruta, Natsumi; Trusov, Yuri; Botella, Jose R.

    2015-01-01

    Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Delivered RNA interference (HD-RNAi) technology to partially silence three different genes (FOW2, FRP1, and OPR) in the hemi-biotrophic fungus F. oxysporum f. sp. conglutinans. Expression of double stranded RNA (dsRNA) molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75, 83, and 72% reduction for FOW2, FRP1, and OPR, respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30–50% survival and OPR between 45 and 70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants. PMID:25654075

  3. New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation

    PubMed Central

    Kieft, Jeffrey S; Rabe, Jennifer L; Chapman, Erich G

    2015-01-01

    Arthropod-borne flaviviruses (FVs) are a growing world-wide health threat whose incidence and range are increasing. The pathogenicity and cytopathicity of these single-stranded RNA viruses are influenced by viral subgenomic non-protein-coding RNAs (sfRNAs) that the viruses produce to high levels during infection. To generate sfRNAs the virus co-opts the action of the abundant cellular exonuclease Xrn1, which is part of the cell's normal RNA turnover machinery. This exploitation of the cellular machinery is enabled by discrete, highly structured, Xrn1-resistant RNA elements (xrRNAs) in the 3′UTR that interact with Xrn1 to halt processive 5′ to 3′ decay of the viral genomic RNA. We recently solved the crystal structure of a functional xrRNA, revealing a novel fold that provides a mechanistic model for Xrn1 resistance. Continued analysis and interpretation of the structure reveals that the tertiary contacts that knit the xrRNA fold together are shared by a wide variety of arthropod-borne FVs, conferring robust Xrn1 resistance in all tested. However, there is some variability in the structures that correlates with unexplained patterns in the viral 3′ UTRs. Finally, examination of these structures and their behavior in the context of viral infection leads to a new hypothesis linking RNA tertiary structure, overall 3′ UTR architecture, sfRNA production, and host adaptation. PMID:26399159

  4. New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation.

    PubMed

    Kieft, Jeffrey S; Rabe, Jennifer L; Chapman, Erich G

    2015-01-01

    Arthropod-borne flaviviruses (FVs) are a growing world-wide health threat whose incidence and range are increasing. The pathogenicity and cytopathicity of these single-stranded RNA viruses are influenced by viral subgenomic non-protein-coding RNAs (sfRNAs) that the viruses produce to high levels during infection. To generate sfRNAs the virus co-opts the action of the abundant cellular exonuclease Xrn1, which is part of the cell's normal RNA turnover machinery. This exploitation of the cellular machinery is enabled by discrete, highly structured, Xrn1-resistant RNA elements (xrRNAs) in the 3'UTR that interact with Xrn1 to halt processive 5' to 3' decay of the viral genomic RNA. We recently solved the crystal structure of a functional xrRNA, revealing a novel fold that provides a mechanistic model for Xrn1 resistance. Continued analysis and interpretation of the structure reveals that the tertiary contacts that knit the xrRNA fold together are shared by a wide variety of arthropod-borne FVs, conferring robust Xrn1 resistance in all tested. However, there is some variability in the structures that correlates with unexplained patterns in the viral 3' UTRs. Finally, examination of these structures and their behavior in the context of viral infection leads to a new hypothesis linking RNA tertiary structure, overall 3' UTR architecture, sfRNA production, and host adaptation. PMID:26399159

  5. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    NASA Astrophysics Data System (ADS)

    Hu, Zongli; Parekh, Urvi; Maruta, Natsumi; Trusov, Yuri; Botella, Jimmy

    2015-01-01

    Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi) technology to partially silence three different genes (FOW2, FRP1 and OPR) in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  6. SOBIR1 contributes to non-host resistance to Magnaporthe oryzae in Arabidopsis.

    PubMed

    Takahashi, Toshiharu; Shibuya, Haruki; Ishikawa, Atsushi

    2016-08-01

    The rate of entry of Magnaporthe oryzae into Arabidopsis pen2 sobir1 plants was significantly higher than that into pen2 plants. The length of the infection hyphae in pen2 sobir1 plants was significantly longer than that in pen2 plants. These results suggest that SOBIR1 is involved in both penetration and post-penetration resistance to M. oryzae in Arabidopsis. PMID:27023441

  7. Resistance to niclosamide in Oncomelania hupensis, the intermediate host of Schistosoma japonicum: should we be worried?

    PubMed

    Dai, Jian-Rong; Li, You-Zi; Wang, Wei; Xing, Yun-Tian; Qu, Guo-Li; Liang, You-Sheng

    2015-02-01

    As the currently only available molluscicide, niclosamide has been widely used for snail control for over 2 decades in China. There is therefore a concern about the emergence of niclosamide-resistant snail populations following repeated, extensive use of the chemical. The purpose of this study was to investigate the likelihood of niclosamide resistance in Oncomelania hupensis in China. Active adult O. hupensis snails derived from 20 counties of 10 schistosomiasis-endemic provinces of China, of 10 snails in each drug concentration, were immersed in solutions of 1, 0.5, 0.25, 0.125, 0.063, 0.032, 0.016 and 0.008 mg L-1 of a 50% wettable powder of niclosamide ethanolamine salt (WPN) for 24 and 48 h at 25 °C, and the median lethal concentration (LC50) was estimated. Then, the 24- and 48-h WPN LC50 values were compared with those determined in the same sampling sites in 2002. The results indicated that the 24- and 48-h WPN LC50 values for O. hupensis were not significantly different from those determined in 2002 (P = 0.202 and 0.796, respectively). It is concluded that the current sensitivity of O. hupensis to niclosamide has not changed after more than 2 decades of repeated, extensive application in the main endemic foci of China, and there is no evidence of resistance to niclosamide detected in O. hupensis. PMID:25003984

  8. Patterns of host-parasite adaptation in three populations of monarch butterflies infected with a naturally occurring protozoan disease: virulence, resistance, and tolerance.

    PubMed

    Sternberg, Eleanore D; Li, Hui; Wang, Rebecca; Gowler, Camden; de Roode, Jacobus C

    2013-12-01

    Many studies have used host-parasite systems to study local adaptation, but few of these studies have found unequivocal evidence for adaptation. One potential reason is that most studies have focused on limited measures of host and parasite fitness that are generally assumed to be under negative frequency-dependent selection. We have used reciprocal cross-infection experiments to test for local adaptation in Hawaiian, south Floridian, and eastern North American populations of monarch butterflies and their protozoan parasites. Sympatric host-parasite combinations did not result in greater host or parasite fitness, as would be expected under coevolutionary dynamics driven by negative frequency-dependent selection. Instead, we found that Hawaiian hosts were more resistant and carried more infective and virulent parasites, which is consistent with theoretical predictions for virulence evolution and coevolutionary arms race dynamics. We also found that Hawaiian hosts were more tolerant, particularly of Hawaiian parasites, indicating that increased resistance does not preclude increased tolerance within a population and that hosts may be more tolerant of local parasites. We did not find a similar pattern in the south Floridian or eastern populations, possibly because host-parasite adaptation occurs within the context of a greater ecological community. PMID:24231547

  9. Ability of the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) to detoxify juglone, the main secondary metabolite of the non-host plant walnut.

    PubMed

    Piskorski, Rafal; Ineichen, Simon; Dorn, Silvia

    2011-10-01

    Many plant species produce toxic secondary metabolites that limit attacks by herbivorous insects, and may thereby constrain insect expansion to new hosts. Walnut is a host for the codling moth Cydia pomonella, which efficiently detoxifies the main walnut defensive compound juglone (5-hydroxy-1,4-naphthoquinone). The oriental fruit moth Grapholita molesta, which also belongs to the tribe Grapholitini, does not feed on walnut. We tested the performance of G. molesta, a highly invasive species, on artificial diets containing juglone at levels mimicking those found in walnut over the growing season. Juglone-fed G. molesta survived relatively well to adulthood, but larval and adult body weights were reduced, and larval developmental time was prolonged in a dose-dependent fashion. Chemical analysis of frass from larvae that had been fed a juglone-containing diet suggests that G. molesta reduces juglone to non-toxic 1,4,5-trihydroxynaphthalene in its gut. This unexpected tolerance of G. molesta to high levels of juglone may facilitate expansion of the host range beyond the current rosacean fruit trees used by this invasive pest. PMID:21901444

  10. Heterogeneity of mprF sequences in methicillin-resistant Staphylococcus aureus clinical isolates: role in cross-resistance between daptomycin and host defense antimicrobial peptides.

    PubMed

    Bayer, Arnold S; Mishra, Nagendra N; Sakoulas, George; Nonejuie, Poochit; Nast, Cynthia C; Pogliano, Joseph; Chen, Kuan-Tsen; Ellison, Steven N; Yeaman, Michael R; Yang, Soo-Jin

    2014-12-01

    Over the past several years, single-nucleotide polymorphisms (SNPs) within the mprF open reading frame (ORF) have been proposed to be associated with a gain-of-function phenotype in terms of daptomycin (DAP) nonsusceptibility (referred to as daptomycin resistance [DAP-R] herein for ease of presentation) in Staphylococcus aureus. We investigated the frequencies of SNPs within the mprF ORF and the relationships of such SNPs to cross-resistance between DAP and cationic host defense peptides (HDPs). Thirty-five well-characterized, unique DAP-susceptible (DAP-S) and DAP-R methicillin-resistant S. aureus (MRSA) isolates of the clonal complex 5 genotype were used. In addition to mprF SNPs and DAP-HDP cross-resistance, several other key genotypic and phenotypic metrics often associated with DAP-R were delineated, as follows: (i) mprF expression, (ii) membrane phospholipid content, (iii) positive surface charge, (iv) DAP binding, and (v) cell wall thickness profiles. A number of DAP-S strains (MICs of ≤ 1 μg/ml) exhibited mprF SNPs, occasionally with high-level mprF sequence variation from the genotype reference strain. However, none of these SNPs were localized to well-chronicled mprF hot spot locations associated with DAP-R in S. aureus. In contrast, all 8 DAP-R isolates demonstrated SNPs within such known mprF hot spots. Moreover, only the DAP-R strains showed MprF gain-of-function phenotypes, enhanced mprF expression, higher survival against two prototypical HDPs, and reduced DAP binding. Although a heterogenous array of mprF SNPs were often found in DAP-S strains, only selected hot spot SNPs, combined with concurrent mprF dysregulation, were associated with the DAP-R phenotype. PMID:25288091

  11. Host resistance of CD18 knockout mice against systemic infection with Listeria monocytogenes

    NASA Technical Reports Server (NTRS)

    Wu, Huaizhu; Prince, Joseph E.; Brayton, Cory F.; Shah, Chirayu; Zeve, Daniel; Gregory, Stephen H.; Smith, C. Wayne; Ballantyne, Christie M.

    2003-01-01

    Mice with targeted mutations of CD18, the common beta2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a gram-positive extracellular bacterium. Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a gram-positive intracellular bacterium. We induced systemic listeriosis in CD18 knockout (CD18-ko) and wild-type (WT) mice by tail vein injection with Listeria. By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (P < 0.01). Quantitative organ culture showed that numbers of Listeria organisms in livers and spleens were similar in both groups at 20 min postinfection. By 3, 5, and 7 dpi, however, numbers of Listeria organisms were significantly lower in livers and spleens of CD18-ko mice than in WT mice. Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice. Cytokine assays indicated that baseline interleukin-1beta and granulocyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT mice and that CD18-ko splenocytes produced higher levels of interleukin-1beta and G-CSF than WT splenocytes under the same amount of Listeria stimulation. These findings show that CD18 is not an absolute requirement for antilisterial innate immunity or hepatic neutrophil recruitment. We propose that the absence of CD18 in the mice results in the priming of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments antilisterial defense.

  12. Host Resistance of CD18 Knockout Mice against Systemic Infection with Listeria monocytogenes

    PubMed Central

    Wu, Huaizhu; Prince, Joseph E.; Brayton, Cory F.; Shah, Chirayu; Zeve, Daniel; Gregory, Stephen H.; Smith, C. Wayne; Ballantyne, Christie M.

    2003-01-01

    Mice with targeted mutations of CD18, the common β2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a gram-positive extracellular bacterium. Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a gram-positive intracellular bacterium. We induced systemic listeriosis in CD18 knockout (CD18-ko) and wild-type (WT) mice by tail vein injection with Listeria. By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (P < 0.01). Quantitative organ culture showed that numbers of Listeria organisms in livers and spleens were similar in both groups at 20 min postinfection. By 3, 5, and 7 dpi, however, numbers of Listeria organisms were significantly lower in livers and spleens of CD18-ko mice than in WT mice. Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice. Cytokine assays indicated that baseline interleukin-1β and granulocyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT mice and that CD18-ko splenocytes produced higher levels of interleukin-1β and G-CSF than WT splenocytes under the same amount of Listeria stimulation. These findings show that CD18 is not an absolute requirement for antilisterial innate immunity or hepatic neutrophil recruitment. We propose that the absence of CD18 in the mice results in the priming of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments antilisterial defense. PMID:14500519

  13. Diversity in Betasatellites Associated with Cotton Leaf Curl Disease During Source-To-Sink Movement Through a Resistant Host.

    PubMed

    Khan, Iftikhar Ali; Akhtar, Khalid Pervaiz; Akbar, Fazal; Hassan, Ishtiaq; Amin, Imran; Saeed, Muhammad; Mansoor, Shahid

    2016-02-01

    Cotton leaf curl is devastating disease of cotton characterized by leaf curling, vein darkening and enations. The disease symptoms are induced by DNA satellite known as Cotton leaf curl Multan betasatellite (CLCuMuB), dominant betasatellite in cotton but another betasatellite known as Chili leaf curl betasatellite (ChLCB) is also found associated with the disease. Grafting experiment was performed to determine if host plant resistance is determinant of dominant population of betasatellite in cotton (several distinct strains of CLCuMuB are associated with the disease). Infected scion of Gossypium hirsutum collected from field (the source) was grafted on G. arboreum, a diploid cotton species, resistant to the disease. A healthy scion of G. hirsutum (sink) was grafted at the top of G. arboreum to determine the movement of virus/betasatellite to upper susceptible scion of G. hirsutum. Symptoms of disease appeared in the upper scion and presence of virus/betasatellite in the upper scion was confirmed via molecular techniques, showing that virus/betasatellite was able to move to upper scion through resistant G. arboreum. However, no symptoms appeared on G. arboreum. Betasatelites were cloned and sequenced from lower scion, upper scion and G. arboreum which show that the lower scion contained both CLCuMuB and ChLCB, however only ChLCB was found in G. arboreum. The upper scion contained CLCuMuB with a deletion of 78 nucleotides (nt) in the non-coding region between A-rich sequence and βC1 gene and insertion of 27 nt in the middle of βC1 ORF. This study may help in investigating molecular basis of resistance in G. arboreum. PMID:26889114

  14. Diversity in Betasatellites Associated with Cotton Leaf Curl Disease During Source-To-Sink Movement Through a Resistant Host

    PubMed Central

    Khan, Iftikhar Ali; Akhtar, Khalid Pervaiz; Akbar, Fazal; Hassan, Ishtiaq; Amin, Imran; Saeed, Muhammad; Mansoor, Shahid

    2016-01-01

    Cotton leaf curl is devastating disease of cotton characterized by leaf curling, vein darkening and enations. The disease symptoms are induced by DNA satellite known as Cotton leaf curl Multan betasatellite (CLCuMuB), dominant betasatellite in cotton but another betasatellite known as Chili leaf curl betasatellite (ChLCB) is also found associated with the disease. Grafting experiment was performed to determine if host plant resistance is determinant of dominant population of betasatellite in cotton (several distinct strains of CLCuMuB are associated with the disease). Infected scion of Gossypium hirsutum collected from field (the source) was grafted on G. arboreum, a diploid cotton species, resistant to the disease. A healthy scion of G. hirsutum (sink) was grafted at the top of G. arboreum to determine the movement of virus/betasatellite to upper susceptible scion of G. hirsutum. Symptoms of disease appeared in the upper scion and presence of virus/betasatellite in the upper scion was confirmed via molecular techniques, showing that virus/betasatellite was able to move to upper scion through resistant G. arboreum. However, no symptoms appeared on G. arboreum. Betasatelites were cloned and sequenced from lower scion, upper scion and G. arboreum which show that the lower scion contained both CLCuMuB and ChLCB, however only ChLCB was found in G. arboreum. The upper scion contained CLCuMuB with a deletion of 78 nucleotides (nt) in the non-coding region between A-rich sequence and βC1 gene and insertion of 27 nt in the middle of βC1 ORF. This study may help in investigating molecular basis of resistance in G. arboreum. PMID:26889114

  15. ST2 as a Marker for Risk of Therapy-Resistant Graft-versus-Host Disease and Death

    PubMed Central

    Vander Lugt, Mark T.; Braun, Thomas M.; Hanash, Samir; Ritz, Jerome; Ho, Vincent T.; Antin, Joseph H.; Zhang, Qing; Wong, Chee-Hong; Wang, Hong; Chin, Alice; Gomez, Aurélie; Harris, Andrew C.; Levine, John E.; Choi, Sung W.; Couriel, Daniel; Reddy, Pavan; Ferrara, James L. M.; Paczesny, Sophie

    2013-01-01

    Background No plasma biomarkers are associated with the response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation. Methods We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation. Results Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95% confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95% CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11% vs. 31% among patients with grade I or II GVHD and 14% vs. 67% among patients with grade III or IV GVHD, P<0.001 for both comparisons). Plasma ST2 values at day 14 after transplantation were associated with 6-month mortality without relapse, regardless of the intensity of the conditioning regimen. Conclusions ST2 levels measured at the initiation of therapy for GVHD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplantation. (Funded by the National Institutes of Health.) PMID:23924003

  16. Aminoglycoside resistance 16S rRNA methyltransferases block endogenous methylation, affect translation efficiency and fitness of the host

    PubMed Central

    Lioy, Virginia S.; Goussard, Sylvie; Guerineau, Vincent; Yoon, Eun-Jeong; Courvalin, Patrice; Galimand, Marc; Grillot-Courvalin, Catherine

    2014-01-01

    In Gram-negative bacteria, acquired 16S rRNA methyltransferases ArmA and NpmA confer high-level resistance to all clinically useful aminoglycosides by modifying, respectively, G1405 and A1408 in the A-site. These enzymes must coexist with several endogenous methyltransferases that are essential for fine-tuning of the decoding center, such as RsmH and RsmI in Escherichia coli, which methylate C1402 and RsmF C1407. The resistance methyltransferases have a contrasting distribution—ArmA has spread worldwide, whereas a single clinical isolate producing NpmA has been reported. The rate of dissemination of resistance depends on the fitness cost associated with its expression. We have compared ArmA and NpmA in isogenic Escherichia coli harboring the corresponding structural genes and their inactive point mutants cloned under the control of their native constitutive promoter in the stable plasmid pGB2. Growth rate determination and competition experiments showed that ArmA had a fitness cost due to methylation of G1405, whereas NpmA conferred only a slight disadvantage to the host due to production of the enzyme. MALDI MS indicated that ArmA impeded one of the methylations at C1402 by RsmI, and not at C1407 as previously proposed, whereas NpmA blocked the activity of RsmF at C1407. A dual luciferase assay showed that methylation at G1405 and A1408 and lack of methylation at C1407 affect translation accuracy. These results indicate that resistance methyltransferases impair endogenous methylation with different consequences on cell fitness. PMID:24398977

  17. Diversification of broad host range plasmids correlates with the presence of antibiotic resistance genes.

    PubMed

    Li, Xiaobin; Wang, Yafei; Brown, Celeste J; Yao, Fei; Jiang, Yong; Top, Eva M; Li, Hui

    2016-01-01

    The IncP-1ε subgroup is a recently identified phylogenetic clade within IncP-1 plasmids, which plays an important role in the spread of antibiotic resistance and degradation of xenobiotic pollutants. Here, four IncP-1ε plasmids were exogenously captured from a petroleum-contaminated habitat in China and compared phylogenetically and genomically with previously reported IncP-1ε and other IncP-1 plasmids. The IncP-1ε plasmids can be clearly subdivided into two subclades, designated as ε-I and ε-II, based on phylogenetic analysis of backbone proteins TraI and TrfA. This was further supported by comparison of concatenated backbone genes. Moreover, the two subclades differed in the transposon types, phenotypes and insertion locations of the accessory elements. The accessory genes on ε-I plasmids were inserted between parA and traC, and harbored ISPa17 and Tn402-like transposon modules, typically carrying antibiotic resistance genes. In contrast, the accessory elements on ε-II plasmids were typically located between trfA and oriV, and contained IS1071, which was commonly inserted within the Tn501-like transposon, typically harboring a cluster of genes encoding mercury resistance and/or catabolic pathways. Our study is one of the first to compare IncP-1 plasmid genomes from China, expands the available collection of IncP-1ε plasmids and enhances our understanding of their diversity, biogeography and evolutionary history. PMID:26635412

  18. Amphotericin B Resistant Apophysomyces elegans Causing Rhino-oculo-Cerebral Mucormycosis in an Immunocompetent Host.

    PubMed

    Biswas, Debasis; Kotwal, Aarti; Kakati, Barnali; Ahmad, Sohaib

    2015-08-01

    Mucormycosis, an angioinvasive infection is caused by the ubiquitous filamentous fungi of the order Mucorales and class Mucormycetes. Reports of this disease are on the rise over the past few decades. Rhino-oculo-Cerebral presentation associated with uncontrolled diabetes is the predominant characteristic of this entity. We report here a case of rhinooculocerebral mucormycosis (ROCM) due to Apophysomyces elegans (A. elegans) in a 45-year-old diabetic lady with background illness of hypothyroidism and polyradiculoneuropathy. Though this condition is usually managed with surgical debridement of the affected tissue and medical therapy with Amphotericin B, the isolate recovered in our case was found to be resistant to Amphotericin B. PMID:26435947

  19. Amphotericin B Resistant Apophysomyces elegans Causing Rhino-oculo-Cerebral Mucormycosis in an Immunocompetent Host

    PubMed Central

    Biswas, Debasis; Kakati, Barnali; Ahmad, Sohaib

    2015-01-01

    Mucormycosis, an angioinvasive infection is caused by the ubiquitous filamentous fungi of the order Mucorales and class Mucormycetes. Reports of this disease are on the rise over the past few decades. Rhino-oculo-Cerebral presentation associated with uncontrolled diabetes is the predominant characteristic of this entity. We report here a case of rhinooculocerebral mucormycosis (ROCM) due to Apophysomyces elegans (A. elegans) in a 45-year-old diabetic lady with background illness of hypothyroidism and polyradiculoneuropathy. Though this condition is usually managed with surgical debridement of the affected tissue and medical therapy with Amphotericin B, the isolate recovered in our case was found to be resistant to Amphotericin B. PMID:26435947

  20. Requirement for CD4+ T Lymphocytes in Host Resistance against Cryptococcus neoformans in the Central Nervous System of Immunized Mice

    PubMed Central

    Buchanan, Kent L.; Doyle, Hester A.

    2000-01-01

    The importance of cell-mediated immunity (CMI) and CD4+ T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4+ T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-γ], CD4+ T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in C. neoformans-infected brains of immune mice. In vivo depletion of CD4+ T cells, but not CD8+ T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4+ T cells or neutralization of IFN-γ exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS. PMID:10639404

  1. Natural Resistance-associated Macrophage Protein (NRAMP) is a cellular receptor for Sindbis virus in both insect and mammalian hosts

    PubMed Central

    Rose, Patrick P.; Hanna, Sheri L.; Spiridigliozzi, Anna; Wannissorn, Nattha; Beiting, Daniel P.; Ross, Susan R.; Hardy, Richard W.; Bambina, Shelly A.; Heise, Mark T.; Cherry, Sara

    2011-01-01

    Summary Alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of for this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter Natural Resistance-Associated Macrophage Protein (NRAMP), as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were non-permissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multi-pass membrane proteins for infection. PMID:21843867

  2. IL-18 triggered by the Nlrp3 inflammasome induces host innate resistance in a pulmonary model of fungal infection.

    PubMed

    Ketelut-Carneiro, Natália; Silva, Grace Kelly; Rocha, Fernanda Agostini; Milanezi, Cristiane Maria; Cavalcanti-Neto, Florêncio Figueiredo; Zamboni, Dario Simões; Silva, João Santana

    2015-05-01

    Pathogens are sensed by innate immune receptors that initiate an efficient adaptive immune response upon activation. The elements of the innate immune recognition process for Paracoccidioides brasiliensis include TLR-2, TLR-4, and dectin-1. However, there are additional receptors necessary for the host immune responses to P. brasiliensis. The nucleotide-binding oligomerization domain-like receptor (NLRs), which activate inflammasomes, are candidate receptors that deserve renewed investigation. After pathogen infection, the NLRs form large signaling platforms called inflammasomes, which lead to caspase-1 activation and maturation of proinflammatory cytokines (IL-18 and IL-1β). In this study, we showed that NLR family pyrin domain-containing 3 (Nlrp3) is required to induce caspase-1 activation and further secretion of IL-1β and IL-18 by P. brasiliensis-infected macrophages. Additionally, potassium efflux and lysosomal acidification induced by the fungus were important steps in the caspase-1 activation mechanism. Notably, Nlrp3 and caspase-1 knockout mice were more susceptible to infection than were the wild-type animals, suggesting that the Nlrp3-dependent inflammasomes contribute to host protection against P. brasiliensis. This protective effect occurred owing to the inflammatory response mediated by IL-18, as shown by an augmented fungus burden in IL-18 knockout mice. Taken together, our results show that the Nlrp3 inflammasome is essential for resistance against P. brasiliensis because it orchestrates robust caspase-1 activation and triggers an IL-18-dependent proinflammatory response. PMID:25825440

  3. Fabrication of a photocontrolled surface with switchable wettability based on host-guest inclusion complexation and protein resistance.

    PubMed

    Shen, Qiongxia; Liu, Lichao; Zhang, Weian

    2014-08-12

    A novel surface-modification strategy has been developed for the construction of a photocontrolled silicon wafer surface with switchable wettability based on host-guest inclusion complexation. The silicon wafer was first modified by guest molecule azobenzene (Azo) via a silanization reaction. Subsequently, a series of polymers with different polarities were attached to host molecule β-cyclodextrin (β-CD) to prepare β-CD-containing hemitelechelic polymers via click chemistry. Finally, a photocontrolled silicon wafer surface modified with polymers was fabricated by inclusion complexation between β-CD and Azo, and the surface properties of the substrate are dependent on the polymers we used. The elemental composition, surface morphology, and hydrophilic/hydrophobic property of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscope, and contact angle measurements, respectively. The antifouling property of the PEG-functionalized surface was evaluated by a protein adsorption assay using bovine serum albumin, which was also characterized by XPS. The results demonstrate that the surface modified with PEG possesses good protein-resistant properties. PMID:25053175

  4. Targeting chitinase gene of Helicoverpa armigera by host-induced RNA interference confers insect resistance in tobacco and tomato.

    PubMed

    Mamta; Reddy, K R K; Rajam, M V

    2016-02-01

    Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a devastating agricultural insect pest with broad spectrum of host range, causing million dollars crop loss annually. Limitations in the present conventional and transgenic approaches have made it crucial to develop sustainable and environmental friendly methods for crop improvement. In the present study, host-induced RNA interference (HI-RNAi) approach was used to develop H. armigera resistant tobacco and tomato plants. Chitinase (HaCHI) gene, critically required for insect molting and metamorphosis was selected as a potential target. Hair-pin RNAi construct was prepared from the conserved off-target free partial HaCHI gene sequence and was used to generate several HaCHI-RNAi tobacco and tomato plants. Northern hybridization confirmed the production of HaCHI gene-specific siRNAs in HaCHI-RNAi tobacco and tomato lines. Continuous feeding on leaves of RNAi lines drastically reduced the target gene transcripts and consequently, affected the overall growth and survival of H. armigera. Various developmental deformities were also manifested in H. armigera larvae after feeding on the leaves of RNAi lines. These results demonstrated the role of chitinase in insect development and potential of HI-RNAi for effective management of H. armigera. PMID:26659592

  5. An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains.

    PubMed

    Alcazar-Fuoli, L; Buitrago, Mj; Gomez-Lopez, A; Mellado, E

    2015-01-01

    Aspergillus fumigatus is the most common mold involved in human infections. However, the number of non-fumigatus species able to cause disease is continuously increasing. Among them, Aspergillus lentulus is reported in hematological and cystic fibrosis patients and in those treated with corticosteroids. A. lentulus differs from A. fumigatus in some clinically relevant aspects such as virulence and antifungal susceptibility, showing high MICs to most antifungals. Previous studies proved that A. lentulus was pathogenic in immunocompromised mice, although the course of the infection was delayed compared to A. fumigatus. These differences could explain why A. lentulus is mostly found in mixed infections with A. fumigatus challenging the diagnosis and treatment. We used the alternative model host Galleria mellonella to compare virulence, host interaction, fungal burden and antifungal response when larvae were infected with A. fumigatus or A. lentulus alone, and with a mixture of both species. A. lentulus was pathogenic in G. mellonella but infected larvae did not respond to therapeutic doses of voriconazole. We were able to simultaneously detect A. fumigatus and A. lentulus by a multiplex Nested Real Time PCR (MN-PCR). Comparative analysis of larvae histological sections showed melanization of both species but presented a different pattern of immune response by haemocytes. Analysis of fungal burden and histology showed that A. lentulus survived in the G. mellonella despite the antifungal treatment in single and mixed infections. We conclude that the simultaneous presence of antifungal susceptible and resistant Aspergillus species would likely complicate the management of these infections. PMID:26065322

  6. Myosins XI modulate host cellular responses and penetration resistance to fungal pathogens

    PubMed Central

    Yang, Long; Qin, Li; Liu, Guosheng; Peremyslov, Valera V.; Dolja, Valerian V.; Wei, Yangdou

    2014-01-01

    The rapid reorganization and polarization of actin filaments (AFs) toward the pathogen penetration site is one of the earliest cellular responses, yet the regulatory mechanism of AF dynamics is poorly understood. Using live-cell imaging in Arabidopsis, we show that polarization coupled with AF bundling involves precise spatiotemporal control at the site of attempted penetration by the nonadapted barley powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We further show that the Bgh-triggered AF mobility and organelle aggregation are predominately driven by the myosin motor proteins. Inactivation of myosins by pharmacological inhibitors prevents bulk aggregation of organelles and blocks recruitment of lignin-like compounds to the penetration site and deposition of callose and defensive protein, PENETRATION 1 (PEN1) into the apoplastic papillae, resulting in attenuation of penetration resistance. Using gene knockout analysis, we demonstrate that highly expressed myosins XI, especially myosin XI-K, are the primary contributors to cell wall-mediated penetration resistance. Moreover, the quadruple myosin knockout mutant xi-1 xi-2 xi-i xi-k displays impaired trafficking pathway responsible for the accumulation of PEN1 at the cell periphery. Strikingly, this mutant shows not only increased penetration rate but also enhanced overall disease susceptibility to both adapted and nonadapted fungal pathogens. Our findings establish myosins XI as key regulators of plant antifungal immunity. PMID:25201952

  7. Rapid and multiregional adaptation to host partial resistance in a plant pathogenic oomycete: evidence from European populations of Plasmopara viticola, the causal agent of grapevine downy mildew.

    PubMed

    Delmotte, François; Mestre, Pere; Schneider, Christophe; Kassemeyer, Hanns-Heinz; Kozma, Pál; Richart-Cervera, Sylvie; Rouxel, Mélanie; Delière, Laurent

    2014-10-01

    Crop pathogens evolve rapidly to adapt to their hosts. The use of crops with quantitative disease resistance is expected to alter selection of pathogen life-history traits. This may result in differential adaptation of the pathogen to host cultivars and, sometimes, to the erosion of quantitative resistance. Here, we assessed the level of host adaptation in an oomycete plant pathogenic species. We analysed the phenotypic and genetic variability of 17 Plasmopara viticola isolates collected on Vitis vinifera and 35 isolates from partially resistant varieties (Regent and genotypes carrying the Rpv1 gene). Cross-inoculation experiments assessed two components of aggressiveness and a life-history trait of the pathogen: disease severity, sporangial production and sporangia size. The results contribute evidence to the emergence of P. viticola aggressive isolates presenting a high level of sporulation on the partially resistant Regent. By contrast, no adaptation to the Rpv1 gene was found in this study. The erosion of Regent resistance may have occurred in less than 5years and at least three times independently in three distant wine-producing areas. Populations from resistant varieties showed a significant increase in sporangia production capacity, indicating an absence of fitness costs for this adaptation. The increase in the number of sporangia was correlated with a reduction in sporangia size, a result which illustrates how partial plant disease resistance can impact selection of the pathogen's life-history traits. This case study on grapevine downy mildew shows how new plant pathogen populations emerge in agro-ecosystems by adapting to partial host resistance. This adaptive pattern highlights the need for wise management of plant partial disease resistance to ensure its sustainability over time. PMID:24184095

  8. Tobamovirus-resistant tobacco generated by RNA interference directed against host genes.

    PubMed

    Asano, Momoko; Satoh, Rena; Mochizuki, Atsuko; Tsuda, Shinya; Yamanaka, Takuya; Nishiguchi, Masamichi; Hirai, Katsuyuki; Meshi, Tetsuo; Naito, Satoshi; Ishikawa, Masayuki

    2005-08-15

    Two homologous Nicotiana tabacum genes NtTOM1 and NtTOM3 have been identified. These genes encode polypeptides with amino acid sequence similarity to Arabidopsis thaliana TOM1 and TOM3, which function in parallel to support tobamovirus multiplication. Simultaneous RNA interference against NtTOM1 and NtTOM3 in N. tabacum resulted in nearly complete inhibition of the multiplication of Tomato mosaic virus and other tobamoviruses, but did not affect plant growth or the ability of Cucumber mosaic virus to multiply. As TOM1 and TOM3 homologues are present in a variety of plant species, their inhibition via RNA interference should constitute a useful method for generating tobamovirus-resistant plants. PMID:16081069

  9. Thiamine induced resistance to Plasmopara viticola in grapevine and elicited host-defense responses, including HR like-cell death.

    PubMed

    Boubakri, Hatem; Wahab, Mohamed Ali; Chong, Julie; Bertsch, Christophe; Mliki, Ahmed; Soustre-Gacougnolle, Isabelle

    2012-08-01

    Recently, thiamine (VitaminB1) has been shown to induce resistance against Pseudomonas syringae in Arabidopsis plants through priming of defense responses. In this paper, we have demonstrated the efficiency of thiamine to induce resistance against downy mildew caused by the oomycete Plasmopara viticola in a susceptible Vitis vinifera cultivar "Chardonnay" under glasshouse controlled conditions by providing a dual mode of action involving direct antifungal activity and elicitation of host-defense responses. Thiamine-induced defense responses included the generation of hydrogen peroxide (H(2)O(2)) in both grapevine suspension cultured cells (SCC) and plant leaves, upregulation of an array of defense-related genes and the induction of other defense responses at subcellular level such as callose deposition in stomata cells, phenolic compounds accumulation and hypersensitive response (HR) like-cell death. Epifluorescence microscopy studies revealed dramatic changes in P. viticola individual developmental stages during its colonization of the intercellular space of the leaf mesophyll in thiamine-treated plants. Collectively, our report evidenced the efficiency of thiamine in the control of downy mildew in grapevine by direct and indirect effects, suggesting that thiamine could be an attractive alternative to chemical fungicides in disease management in vineyards. PMID:22698755

  10. Stevens-Johnson syndrome-like exanthema secondary to methotrexate histologically simulating acute graft-versus-host disease.

    PubMed

    Hani, N; Casper, C; Groth, W; Krieg, T; Hunzelmann, N

    2000-01-01

    A 61 year old male patient suffering from psoriasis vulgaris developed a severe skin reaction with toxic myelosuppression three days after administration of 20 mg methotrexate (MTX) p.o. per week and concomitant 100 mg acetylic salicylic acid (ASA) per day. The skin lesions simulated Stevens-Johnson syndrome with ulcerations of the oral mucosa and erythema multiforme-like target lesions. The histology of the epidermis resembled an acute graft-versus-host reaction. The increased toxic effect of MTX on keratinocytes in our patient was most likely caused by a lowered plasma binding capacity and reduced renal excretion of MTX due to concomitant administration of ASA. Thus in the treatment of severe forms of psoriasis with MTX, the combined administration of drugs aggravating MTX toxicity, particularly of ASA, should be carefully considered, due to the increased toxicity and risk of severe skin reactions. PMID:11056429