Science.gov

Sample records for host interactions reveals

  1. Revealing the molecular signatures of host-pathogen interactions

    PubMed Central

    2011-01-01

    Advances in sequencing technology and genome-wide association studies are now revealing the complex interactions between hosts and pathogen through genomic variation signatures, which arise from evolutionary co-existence. PMID:22011345

  2. Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex Metabolic Interactions with the Host Cell

    PubMed Central

    Skliros, Dimitrios; Kalatzis, Panos G.; Katharios, Pantelis; Flemetakis, Emmanouil

    2016-01-01

    Sequencing and annotation was performed for two large double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage–host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other large Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the “schizoT4like” clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral open reading frames (ORFs) participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection. PMID:27895630

  3. Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex Metabolic Interactions with the Host Cell.

    PubMed

    Skliros, Dimitrios; Kalatzis, Panos G; Katharios, Pantelis; Flemetakis, Emmanouil

    2016-01-01

    Sequencing and annotation was performed for two large double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage-host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other large Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the "schizoT4like" clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral open reading frames (ORFs) participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number of genes involved in auxiliary NAD(+) and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection.

  4. Lassa Virus Cell Entry Reveals New Aspects of Virus-Host Cell Interaction.

    PubMed

    Torriani, Giulia; Galan-Navarro, Clara; Kunz, Stefan

    2017-02-15

    Viral entry represents the first step of every viral infection and is a determinant for the host range and disease potential of a virus. Here, we review the latest developments on cell entry of the highly pathogenic Old World arenavirus Lassa virus, providing novel insights into the complex virus-host cell interaction of this important human pathogen. We will cover new discoveries on the molecular mechanisms of receptor recognition, endocytosis, and the use of late endosomal entry factors.

  5. Modified inoculation and disease assessment methods reveal host specificity in Erwinia tracheiphila-Cucurbitaceae interactions.

    PubMed

    Nazareno, Eric S; Dumenyo, C Korsi

    2015-12-01

    We conducted a greenhouse trial to determine specific compatible interactions between Erwinia tracheiphila strains and cucurbit host species. Using a modified inoculation system, E. tracheiphila strains HCa1-5N, UnisCu1-1N, and MISpSq-N were inoculated to cucumber (Cucumis sativus) cv. 'Sweet Burpless', melon (Cucumis melo) cv. 'Athena Hybrid', and squash (Cucubita pepo) cv. 'Early Summer Crookneck'. We observed symptoms and disease progression for 30 days; recorded the number of days to wilting of the inoculated leaf (DWIL), days to wilting of the whole plant (DWWP), and days to death of the plant (DDP). We found significant interactions between host cultivar and pathogen strains, which imply host specificity. Pathogen strains HCa1-5N and UnisCu1-1N isolated from Cucumis species exhibited more virulence in cucumber and melon than in squash, while the reverse was true for strain MISpSq-N, an isolate from Cucurbita spp. Our observations confirm a previous finding that E. tracheiphila strains isolated from Cucumis species were more virulent on Cucumis hosts and those from Cucubita were more virulent on Cucubita hosts. This confirmation helps in better understanding the pathosystem and provides baseline information for the subsequent development of new disease management strategies for bacterial wilt. We also demonstrated the efficiency of our modified inoculation and disease scoring methods.

  6. Analysis of virus genomes from glacial environments reveals novel virus groups with unusual host interactions.

    PubMed

    Bellas, Christopher M; Anesio, Alexandre M; Barker, Gary

    2015-01-01

    Microbial communities in glacial ecosystems are diverse, active, and subjected to strong viral pressures and infection rates. In this study we analyse putative virus genomes assembled from three dsDNA viromes from cryoconite hole ecosystems of Svalbard and the Greenland Ice Sheet to assess the potential hosts and functional role viruses play in these habitats. We assembled 208 million reads from the virus-size fraction and developed a procedure to select genuine virus scaffolds from cellular contamination. Our curated virus library contained 546 scaffolds up to 230 Kb in length, 54 of which were circular virus consensus genomes. Analysis of virus marker genes revealed a wide range of viruses had been assembled, including bacteriophages, cyanophages, nucleocytoplasmic large DNA viruses and a virophage, with putative hosts identified as Cyanobacteria, Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes, eukaryotic algae and amoebae. Whole genome comparisons revealed the majority of circular genome scaffolds (CGS) formed 12 novel groups, two of which contained multiple phage members with plasmid-like properties, including a group of phage-plasmids possessing plasmid-like partition genes and toxin-antitoxin addiction modules to ensure their replication and a satellite phage-plasmid group. Surprisingly we also assembled a phage that not only encoded plasmid partition genes, but a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas adaptive bacterial immune system. One of the spacers was an exact match for another phage in our virome, indicating that in a novel use of the system, the lysogen was potentially capable of conferring immunity on its bacterial host against other phage. Together these results suggest that highly novel and diverse groups of viruses are present in glacial environments, some of which utilize very unusual life strategies and genes to control their replication and maintain a long-term relationship with their hosts.

  7. Analysis of virus genomes from glacial environments reveals novel virus groups with unusual host interactions

    PubMed Central

    Bellas, Christopher M.; Anesio, Alexandre M.; Barker, Gary

    2015-01-01

    Microbial communities in glacial ecosystems are diverse, active, and subjected to strong viral pressures and infection rates. In this study we analyse putative virus genomes assembled from three dsDNA viromes from cryoconite hole ecosystems of Svalbard and the Greenland Ice Sheet to assess the potential hosts and functional role viruses play in these habitats. We assembled 208 million reads from the virus-size fraction and developed a procedure to select genuine virus scaffolds from cellular contamination. Our curated virus library contained 546 scaffolds up to 230 Kb in length, 54 of which were circular virus consensus genomes. Analysis of virus marker genes revealed a wide range of viruses had been assembled, including bacteriophages, cyanophages, nucleocytoplasmic large DNA viruses and a virophage, with putative hosts identified as Cyanobacteria, Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes, eukaryotic algae and amoebae. Whole genome comparisons revealed the majority of circular genome scaffolds (CGS) formed 12 novel groups, two of which contained multiple phage members with plasmid-like properties, including a group of phage-plasmids possessing plasmid-like partition genes and toxin-antitoxin addiction modules to ensure their replication and a satellite phage-plasmid group. Surprisingly we also assembled a phage that not only encoded plasmid partition genes, but a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas adaptive bacterial immune system. One of the spacers was an exact match for another phage in our virome, indicating that in a novel use of the system, the lysogen was potentially capable of conferring immunity on its bacterial host against other phage. Together these results suggest that highly novel and diverse groups of viruses are present in glacial environments, some of which utilize very unusual life strategies and genes to control their replication and maintain a long-term relationship with their hosts

  8. Combining genomic sequencing methods to explore viral diversity and reveal potential virus-host interactions

    PubMed Central

    Chow, Cheryl-Emiliane T.; Winget, Danielle M.; White, Richard A.; Hallam, Steven J.; Suttle, Curtis A.

    2015-01-01

    Viral diversity and virus-host interactions in oxygen-starved regions of the ocean, also known as oxygen minimum zones (OMZs), remain relatively unexplored. Microbial community metabolism in OMZs alters nutrient and energy flow through marine food webs, resulting in biological nitrogen loss and greenhouse gas production. Thus, viruses infecting OMZ microbes have the potential to modulate community metabolism with resulting feedback on ecosystem function. Here, we describe viral communities inhabiting oxic surface (10 m) and oxygen-starved basin (200 m) waters of Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia using viral metagenomics and complete viral fosmid sequencing on samples collected between April 2007 and April 2010. Of 6459 open reading frames (ORFs) predicted across all 34 viral fosmids, 77.6% (n = 5010) had no homology to reference viral genomes. These fosmids recruited a higher proportion of viral metagenomic sequences from Saanich Inlet than from nearby northeastern subarctic Pacific Ocean (Line P) waters, indicating differences in the viral communities between coastal and open ocean locations. While functional annotations of fosmid ORFs were limited, recruitment to NCBI's non-redundant “nr” database and publicly available single-cell genomes identified putative viruses infecting marine thaumarchaeal and SUP05 proteobacteria to provide potential host linkages with relevance to coupled biogeochemical cycling processes in OMZ waters. Taken together, these results highlight the power of coupled analyses of multiple sequence data types, such as viral metagenomic and fosmid sequence data with prokaryotic single cell genomes, to chart viral diversity, elucidate genomic and ecological contexts for previously unclassifiable viral sequences, and identify novel host interactions in natural and engineered ecosystems. PMID:25914678

  9. Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

    PubMed Central

    Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D.

    2016-01-01

    Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses. PMID:27808111

  10. Complex Evolutionary History of the Aeromonas veronii Group Revealed by Host Interaction and DNA Sequence Data

    PubMed Central

    Faucher, Joshua; Horneman, Amy J.; Gogarten, J. Peter; Graf, Joerg

    2011-01-01

    Aeromonas veronii biovar sobria, Aeromonas veronii biovar veronii, and Aeromonas allosaccharophila are a closely related group of organisms, the Aeromonas veronii Group, that inhabit a wide range of host animals as a symbiont or pathogen. In this study, the ability of various strains to colonize the medicinal leech as a model for beneficial symbiosis and to kill wax worm larvae as a model for virulence was determined. Isolates cultured from the leech out-competed other strains in the leech model, while most strains were virulent in the wax worms. Three housekeeping genes, recA, dnaJ and gyrB, the gene encoding chitinase, chiA, and four loci associated with the type three secretion system, ascV, ascFG, aexT, and aexU were sequenced. The phylogenetic reconstruction failed to produce one consensus tree that was compatible with most of the individual genes. The Approximately Unbiased test and the Genetic Algorithm for Recombination Detection both provided further support for differing evolutionary histories among this group of genes. Two contrasting tests detected recombination within aexU, ascFG, ascV, dnaJ, and gyrB but not in aexT or chiA. Quartet decomposition analysis indicated a complex recent evolutionary history for these strains with a high frequency of horizontal gene transfer between several but not among all strains. In this study we demonstrate that at least for some strains, horizontal gene transfer occurs at a sufficient frequency to blur the signal from vertically inherited genes, despite strains being adapted to distinct niches. Simply increasing the number of genes included in the analysis is unlikely to overcome this challenge in organisms that occupy multiple niches and can exchange DNA between strains specialized to different niches. Instead, the detection of genes critical in the adaptation to specific niches may help to reveal the physiological specialization of these strains. PMID:21359176

  11. Complex evolutionary history of the Aeromonas veronii group revealed by host interaction and DNA sequence data.

    PubMed

    Silver, Adam C; Williams, David; Faucher, Joshua; Horneman, Amy J; Gogarten, J Peter; Graf, Joerg

    2011-02-16

    Aeromonas veronii biovar sobria, Aeromonas veronii biovar veronii, and Aeromonas allosaccharophila are a closely related group of organisms, the Aeromonas veronii Group, that inhabit a wide range of host animals as a symbiont or pathogen. In this study, the ability of various strains to colonize the medicinal leech as a model for beneficial symbiosis and to kill wax worm larvae as a model for virulence was determined. Isolates cultured from the leech out-competed other strains in the leech model, while most strains were virulent in the wax worms. Three housekeeping genes, recA, dnaJ and gyrB, the gene encoding chitinase, chiA, and four loci associated with the type three secretion system, ascV, ascFG, aexT, and aexU were sequenced. The phylogenetic reconstruction failed to produce one consensus tree that was compatible with most of the individual genes. The Approximately Unbiased test and the Genetic Algorithm for Recombination Detection both provided further support for differing evolutionary histories among this group of genes. Two contrasting tests detected recombination within aexU, ascFG, ascV, dnaJ, and gyrB but not in aexT or chiA. Quartet decomposition analysis indicated a complex recent evolutionary history for these strains with a high frequency of horizontal gene transfer between several but not among all strains. In this study we demonstrate that at least for some strains, horizontal gene transfer occurs at a sufficient frequency to blur the signal from vertically inherited genes, despite strains being adapted to distinct niches. Simply increasing the number of genes included in the analysis is unlikely to overcome this challenge in organisms that occupy multiple niches and can exchange DNA between strains specialized to different niches. Instead, the detection of genes critical in the adaptation to specific niches may help to reveal the physiological specialization of these strains.

  12. Viral-host interaction in kidney reveals strategies to escape host immunity and persistently shed virus to the urine.

    PubMed

    Ou, Xumin; Mao, Sai; Jiang, Yifan; Zhang, Shengyong; Ke, Chen; Ma, Guangpeng; Cheng, Anchun; Wang, Mingshu; Zhu, Dekang; Chen, Shun; Jia, Renyong; Liu, Mafeng; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue

    2017-01-31

    Hepatitis A virus is one of five types of hepatotropic viruses that cause human liver disease. A similar liver disease is also identified in ducks caused by Duck Hepatitis A virus (DHAV). Notably, many types of hepatotropic viruses can be detected in urine. However, how those viruses enter into the urine is largely unexplored. To elucidate the potential mechanism, we used the avian hepatotropic virus to investigate replication strategies and immune responses in kidney until 280 days after infection. Immunohistochemistry and qPCR were used to detect viral distribution and copies in the kidney. Double staining of CD4+ or CD8+ T cells and virus and qPCR were used to investigate T cell immune responses and expression levels of cytokines. Histopathology was detected by standard HE staining. In this study, viruses were persistently located at scattered renal tubules. No CD4+ or CD8+ T cells were recruited to the kidney, which was only accompanied by transient cytokine storms. In conclusion, the extremely scattered infection was the viral strategy to escape host immunity and may persistently shed virus into urine. The deletion of Th or Tc cell responses and transient cytokine storms indeed provide an advantageous renal environment for their persistent survival.

  13. The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions

    PubMed Central

    Shitrit, Alina; Shani, Odem; Le-Trilling, Vu Thuy Khanh; Trilling, Mirko; Friedlander, Gilgi; Tanenbaum, Marvin; Stern-Ginossar, Noam

    2015-01-01

    Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus. PMID:26599541

  14. Receptor binding and cell entry of Old World arenaviruses reveal novel aspects of virus-host interaction.

    PubMed

    Kunz, Stefan

    2009-05-10

    Ten years ago, the first cellular receptor for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and the highly pathogenic Lassa virus (LASV) was identified as alpha-dystroglycan (alpha-DG), a versatile receptor for proteins of the extracellular matrix (ECM). Biochemical analysis of the interaction of alpha-DG with arenaviruses and ECM proteins revealed a strikingly similar mechanism of receptor recognition that critically depends on specific sugar modification on alpha-DG involving a novel class of putative glycosyltransferase, the LARGE proteins. Interestingly, recent genome-wide detection and characterization of positive selection in human populations revealed evidence for positive selection of a locus within the LARGE gene in populations from Western Africa, where LASV is endemic. While most enveloped viruses that enter the host cell in a pH-dependent manner use clathrin-mediated endocytosis, recent studies revealed that the Old World arenaviruses LCMV and LASV enter the host cell predominantly via a novel and unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the virus is rapidly delivered to endosomes via an unusual route of vesicular trafficking that is largely independent of the small GTPases Rab5 and Rab7. Since infection of cells with LCMV and LASV depends on DG, this unusual endocytotic pathway could be related to normal cellular trafficking of the DG complex. Alternatively, engagement of arenavirus particles may target DG for an endocytotic pathway not normally used in uninfected cells thereby inducing an entry route specifically tailored to the pathogen's needs.

  15. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells

    PubMed Central

    Song, BenBen; Zhou, Jianhua; Wang, Tony T.

    2016-01-01

    Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection. PMID:26808496

  16. Metatranscriptome analysis reveals host-microbiome interactions in traps of carnivorous Genlisea species

    PubMed Central

    Cao, Hieu X.; Schmutzer, Thomas; Scholz, Uwe; Pecinka, Ales; Schubert, Ingo; Vu, Giang T. H.

    2015-01-01

    In the carnivorous plant genus Genlisea a unique lobster pot trapping mechanism supplements nutrition in nutrient-poor habitats. A wide spectrum of microbes frequently occurs in Genlisea's leaf-derived traps without clear relevance for Genlisea carnivory. We sequenced the metatranscriptomes of subterrestrial traps vs. the aerial chlorophyll-containing leaves of G. nigrocaulis and of G. hispidula. Ribosomal RNA assignment revealed soil-borne microbial diversity in Genlisea traps, with 92 genera of 19 phyla present in more than one sample. Microbes from 16 of these phyla including proteobacteria, green algae, amoebozoa, fungi, ciliates and metazoans, contributed additionally short-lived mRNA to the metatranscriptome. Furthermore, transcripts of 438 members of hydrolases (e.g., proteases, phosphatases, lipases), mainly resembling those of metazoans, ciliates and green algae, were found. Compared to aerial leaves, Genlisea traps displayed a transcriptional up-regulation of endogenous NADH oxidases generating reactive oxygen species as well as of acid phosphatases for prey digestion. A leaf-vs.-trap transcriptome comparison reflects that carnivory provides inorganic P- and different forms of N-compounds (ammonium, nitrate, amino acid, oligopeptides) and implies the need to protect trap cells against oxidative stress. The analysis elucidates a complex food web inside the Genlisea traps, and suggests ecological relationships between this plant genus and its entrapped microbiome. PMID:26236284

  17. Genome sequencing and comparative genomics of honey bee microsporidia, Nosema apis reveal novel insights into host-parasite interactions

    PubMed Central

    2013-01-01

    Background The microsporidia parasite Nosema contributes to the steep global decline of honey bees that are critical pollinators of food crops. There are two species of Nosema that have been found to infect honey bees, Nosema apis and N. ceranae. Genome sequencing of N. apis and comparative genome analysis with N. ceranae, a fully sequenced microsporidia species, reveal novel insights into host-parasite interactions underlying the parasite infections. Results We applied the whole-genome shotgun sequencing approach to sequence and assemble the genome of N. apis which has an estimated size of 8.5 Mbp. We predicted 2,771 protein- coding genes and predicted the function of each putative protein using the Gene Ontology. The comparative genomic analysis led to identification of 1,356 orthologs that are conserved between the two Nosema species and genes that are unique characteristics of the individual species, thereby providing a list of virulence factors and new genetic tools for studying host-parasite interactions. We also identified a highly abundant motif in the upstream promoter regions of N. apis genes. This motif is also conserved in N. ceranae and other microsporidia species and likely plays a role in gene regulation across the microsporidia. Conclusions The availability of the N. apis genome sequence is a significant addition to the rapidly expanding body of microsprodian genomic data which has been improving our understanding of eukaryotic genome diversity and evolution in a broad sense. The predicted virulent genes and transcriptional regulatory elements are potential targets for innovative therapeutics to break down the life cycle of the parasite. PMID:23829473

  18. Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions

    PubMed Central

    2011-01-01

    Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary

  19. The Structure of Treponema pallidum Tp0751 (Pallilysin) Reveals a Non-canonical Lipocalin Fold That Mediates Adhesion to Extracellular Matrix Components and Interactions with Host Cells

    PubMed Central

    Pětrošová, Helena; Lithgow, Karen V.; Hof, Rebecca; Wetherell, Charmaine; Kao, Wei-Chien; Lin, Yi-Pin; Ebady, Rhodaba; Cameron, Caroline E.

    2016-01-01

    Syphilis is a chronic disease caused by the bacterium Treponema pallidum subsp. pallidum. Treponema pallidum disseminates widely throughout the host and extravasates from the vasculature, a process that is at least partially dependent upon the ability of T. pallidum to interact with host extracellular matrix (ECM) components. Defining the molecular basis for the interaction between T. pallidum and the host is complicated by the intractability of T. pallidum to in vitro culturing and genetic manipulation. Correspondingly, few T. pallidum proteins have been identified that interact directly with host components. Of these, Tp0751 (also known as pallilysin) displays a propensity to interact with the ECM, although the underlying mechanism of these interactions remains unknown. Towards establishing the molecular mechanism of Tp0751-host ECM attachment, we first determined the crystal structure of Tp0751 to a resolution of 2.15 Å using selenomethionine phasing. Structural analysis revealed an eight-stranded beta-barrel with a profile of short conserved regions consistent with a non-canonical lipocalin fold. Using a library of native and scrambled peptides representing the full Tp0751 sequence, we next identified a subset of peptides that showed statistically significant and dose-dependent interactions with the ECM components fibrinogen, fibronectin, collagen I, and collagen IV. Intriguingly, each ECM-interacting peptide mapped to the lipocalin domain. To assess the potential of these ECM-coordinating peptides to inhibit adhesion of bacteria to host cells, we engineered an adherence-deficient strain of the spirochete Borrelia burgdorferi to heterologously express Tp0751. This engineered strain displayed Tp0751 on its surface and exhibited a Tp0751-dependent gain-of-function in adhering to human umbilical vein endothelial cells that was inhibited in the presence of one of the ECM-interacting peptides (p10). Overall, these data provide the first structural insight into the

  20. Genome and metagenome analyses reveal adaptive evolution of the host and interaction with the gut microbiota in the goose

    PubMed Central

    Gao, Guangliang; Zhao, Xianzhi; Li, Qin; He, Chuan; Zhao, Wenjing; Liu, Shuyun; Ding, Jinmei; Ye, Weixing; Wang, Jun; Chen, Ye; Wang, Haiwei; Li, Jing; Luo, Yi; Su, Jian; Huang, Yong; Liu, Zuohua; Dai, Ronghua; Shi, Yixiang; Meng, He; Wang, Qigui

    2016-01-01

    The goose is an economically important waterfowl that exhibits unique characteristics and abilities, such as liver fat deposition and fibre digestion. Here, we report de novo whole-genome assemblies for the goose and swan goose and describe the evolutionary relationships among 7 bird species, including domestic and wild geese, which diverged approximately 3.4~6.3 million years ago (Mya). In contrast to chickens as a proximal species, the expanded and rapidly evolving genes found in the goose genome are mainly involved in metabolism, including energy, amino acid and carbohydrate metabolism. Further integrated analysis of the host genome and gut metagenome indicated that the most widely shared functional enrichment of genes occurs for functions such as glycolysis/gluconeogenesis, starch and sucrose metabolism, propanoate metabolism and the citrate cycle. We speculate that the unique physiological abilities of geese benefit from the adaptive evolution of the host genome and symbiotic interactions with gut microbes. PMID:27608918

  1. A yeast two-hybrid screen reveals a strong interaction between the Legionella chaperonin Hsp60 and the host cell small heat shock protein Hsp10.

    PubMed

    Nasrallah, Gheyath K

    2015-06-01

    L. pneumophila is an intracellular bacterium that replicates inside a membrane-bound vacuole called Legionella-containing vacuole (LCV), where it plentifully liberates its HtpB chaperonin. From LCV, HtpB reaches the host cell cytoplasm, where it interacts with SAMDC, a cytoplasmic protein required for synthesis of host polyamines that are important for intracellular growth of L. pneumophila. Additionally, cytoplasmic expression of HtpB in S. cerevisiae induces pseudohyphal growth, and in mammalian cells recruits mitochondria to LCV, and modifies actin microfilaments organization. This led us to hypothesize here that HtpB recruits a protein(s) from eukaryotic cells that is involved in the emergence of the aforementioned phenotypes. To identify this protein, a commercially available HeLa cDNA library was screened using a yeast two-hybrid system. Approximately 5×10(6) yeast clones carrying HeLa cDNA library plasmid were screened. Twenty-one positive clones were identified. DNA sequence analysis revealed that all of these positive clones encoded the mammalian small heat shock protein Hsp10. Based on the fact that chaperonions are required to interact with co-chaperonins to function properly in protein folding, we believe that HtpB recruits the host cell Hsp10 to appropriately interact with SAMDC and to induce the multifunction phenotypes deemed important in L. pneumophila pathogenesis.

  2. Evans Blue Staining Reveals Vascular Leakage Associated with Focal Areas of Host-Parasite Interaction in Brains of Pigs Infected with Taenia solium

    PubMed Central

    Paredes, Adriana; Cangalaya, Carla; Rivera, Andrea; Gonzalez, Armando E.; Mahanty, Siddhartha; Garcia, Hector H.; Nash, Theodore E.

    2014-01-01

    Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads to an acute pericystic host inflammatory response and blood brain barrier breakdown (BBB), commonly resulting in seizures. Naturally infected pigs, untreated or treated one time with praziquantel were sacrificed at 48 hr and 120 hr following the injection of Evans blue (EB) to assess the effect of treatment on larval parasites and surrounding tissue. Examination of harvested non encapsulated muscle cysts unexpectedly revealed one or more small, focal round region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas of eosinophil-rich inflammatory infiltrates that migrated from the capsule into the tegument and internal structures of the parasite. In addition some encapsulated brain cysts, in which the presence of REBI could not be directly assessed, showed histopathology identical to that of the REBI. Muscle cysts with REBI were more frequent in pigs that had received praziquantel (6.6% of 3736 cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2 pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed histopathology identical to muscle REBI cysts in praziquantel-treated pigs compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI infiltrates showed that EB was taken up only by eosinophils, a major component of the cellular infiltrates, which likely explains persistence of EB in the REBI. REBI likely represent early damaging host responses to T. solium cysts and highlight the focal nature of this initial host response and the importance of eosinophils at sites of host-parasite interaction. These findings suggest new avenues for immunomodulation to reduce inflammatory side effects of anthelmintic therapy. PMID:24915533

  3. Evans blue staining reveals vascular leakage associated with focal areas of host-parasite interaction in brains of pigs infected with Taenia solium.

    PubMed

    Marzal, Miguel; Guerra-Giraldez, Cristina; Paredes, Adriana; Cangalaya, Carla; Rivera, Andrea; Gonzalez, Armando E; Mahanty, Siddhartha; Garcia, Hector H; Nash, Theodore E

    2014-01-01

    Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads to an acute pericystic host inflammatory response and blood brain barrier breakdown (BBB), commonly resulting in seizures. Naturally infected pigs, untreated or treated one time with praziquantel were sacrificed at 48 hr and 120 hr following the injection of Evans blue (EB) to assess the effect of treatment on larval parasites and surrounding tissue. Examination of harvested non encapsulated muscle cysts unexpectedly revealed one or more small, focal round region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas of eosinophil-rich inflammatory infiltrates that migrated from the capsule into the tegument and internal structures of the parasite. In addition some encapsulated brain cysts, in which the presence of REBI could not be directly assessed, showed histopathology identical to that of the REBI. Muscle cysts with REBI were more frequent in pigs that had received praziquantel (6.6% of 3736 cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2 pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed histopathology identical to muscle REBI cysts in praziquantel-treated pigs compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI infiltrates showed that EB was taken up only by eosinophils, a major component of the cellular infiltrates, which likely explains persistence of EB in the REBI. REBI likely represent early damaging host responses to T. solium cysts and highlight the focal nature of this initial host response and the importance of eosinophils at sites of host-parasite interaction. These findings suggest new avenues for immunomodulation to reduce inflammatory side effects of anthelmintic therapy.

  4. Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions*

    PubMed Central

    Khatri, Kshitij; Klein, Joshua A.; White, Mitchell R.; Grant, Oliver C.; Leymarie, Nancy; Woods, Robert J.; Zaia, Joseph

    2016-01-01

    Despite sustained biomedical research effort, influenza A virus remains an imminent threat to the world population and a major healthcare burden. The challenge in developing vaccines against influenza is the ability of the virus to mutate rapidly in response to selective immune pressure. Hemagglutinin is the predominant surface glycoprotein and the primary determinant of antigenicity, virulence and zoonotic potential. Mutations leading to changes in the number of HA glycosylation sites are often reported. Such genetic sequencing studies predict at best the disruption or creation of sequons for N-linked glycosylation; they do not reflect actual phenotypic changes in HA structure. Therefore, combined analysis of glycan micro and macro-heterogeneity and bioassays will better define the relationships among glycosylation, viral bioactivity and evolution. We present a study that integrates proteomics, glycomics and glycoproteomics of HA before and after adaptation to innate immune system pressure. We combined this information with glycan array and immune lectin binding data to correlate the phenotypic changes with biological activity. Underprocessed glycoforms predominated at the glycosylation sites found to be involved in viral evolution in response to selection pressures and interactions with innate immune-lectins. To understand the structural basis for site-specific glycan microheterogeneity at these sites, we performed structural modeling and molecular dynamics simulations. We observed that the presence of immature, high-mannose type glycans at a particular site correlated with reduced accessibility to glycan remodeling enzymes. Further, the high mannose glycans at sites implicated in immune lectin recognition were predicted to be capable of forming trimeric interactions with the immune-lectin surfactant protein-D. PMID:26984886

  5. The 2.15 A crystal structure of Mycobacterium tuberculosis chorismate mutase reveals an unexpected gene duplication and suggests a role in host-pathogen interactions.

    PubMed

    Qamra, Rohini; Prakash, Prachee; Aruna, Bandi; Hasnain, Seyed E; Mande, Shekhar C

    2006-06-13

    Chorismate mutase catalyzes the first committed step toward the biosynthesis of the aromatic amino acids, phenylalanine and tyrosine. While this biosynthetic pathway exists exclusively in the cell cytoplasm, the Mycobacterium tuberculosis enzyme has been shown to be secreted into the extracellular medium. The secretory nature of the enzyme and its existence in M. tuberculosis as a duplicated gene are suggestive of its role in host-pathogen interactions. We report here the crystal structure of homodimeric chorismate mutase (Rv1885c) from M. tuberculosis determined at 2.15 A resolution. The structure suggests possible gene duplication within each subunit of the dimer (residues 35-119 and 130-199) and reveals an interesting proline-rich region on the protein surface (residues 119-130), which might act as a recognition site for protein-protein interactions. The structure also offers an explanation for its regulation by small ligands, such as tryptophan, a feature previously unknown in the prototypical Escherichia coli chorismate mutase. The tryptophan ligand is found to be sandwiched between the two monomers in a dimer contacting residues 66-68. The active site in the "gene-duplicated" monomer is occupied by a sulfate ion and is located in the first half of the polypeptide, unlike in the Saccharomyces cerevisiae (yeast) enzyme, where it is located in the later half. We hypothesize that the M. tuberculosis chorismate mutase might have a role to play in host-pathogen interactions, making it an important target for designing inhibitor molecules against the deadly pathogen.

  6. Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion

    PubMed Central

    Tenor, Jennifer L.; Oehlers, Stefan H.; Yang, Jialu L.

    2015-01-01

    ABSTRACT The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of Cryptococcus mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that C. neoformans is able to penetrate the zebrafish brain following intravenous infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformans platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. PMID:26419880

  7. Meningococcal interactions with the host.

    PubMed

    Carbonnelle, Etienne; Hill, Darryl J; Morand, Philippe; Griffiths, Natalie J; Bourdoulous, Sandrine; Murillo, Isabel; Nassif, Xavier; Virji, Mumtaz

    2009-06-24

    Neisseria meningitidis interacts with host tissues through hierarchical, concerted and co-ordinated actions of a number of adhesins; many of which undergo antigenic and phase variation, a strategy that helps immune evasion. Three major structures, pili, Opa and Opc predominantly influence bacterial adhesion to host cells. Pili and Opa proteins also determine host and tissue specificity while Opa and Opc facilitate efficient cellular invasion. Recent studies have also implied a role of certain adhesin-receptor pairs in determining increased host susceptibility to infection. This chapter examines our current knowledge of meningococcal adhesion and invasion mechanisms particularly related to human epithelial and endothelial cells which are of primary importance in the disease process.

  8. A Profile of an Endosymbiont-enriched Fraction of the Coral Stylophora pistillata Reveals Proteins Relevant to Microbial-Host Interactions*

    PubMed Central

    Weston, Andrew J.; Dunlap, Walter C.; Shick, J. Malcolm; Klueter, Anke; Iglic, Katrina; Vukelic, Ana; Starcevic, Antonio; Ward, Malcolm; Wells, Mark L.; Trick, Charles G.; Long, Paul F.

    2012-01-01

    This study examines the response of Symbiodinium sp. endosymbionts from the coral Stylophora pistillata to moderate levels of thermal “bleaching” stress, with and without trace metal limitation. Using quantitative high throughput proteomics, we identified 8098 MS/MS events relating to individual peptides from the endosymbiont-enriched fraction, including 109 peptides meeting stringent criteria for quantification, of which only 26 showed significant change in our experimental treatments; 12 of 26 increased expression in response to thermal stress with little difference affected by iron limitation. Surprisingly, there were no significant increases in antioxidant or heat stress proteins; those induced to higher expression were generally involved in protein biosynthesis. An outstanding exception was a massive 114-fold increase of a viral replication protein indicating that thermal stress may substantially increase viral load and thereby contribute to the etiology of coral bleaching and disease. In the absence of a sequenced genome for Symbiodinium or other photosymbiotic dinoflagellate, this proteome reveals a plethora of proteins potentially involved in microbial-host interactions. This includes photosystem proteins, DNA repair enzymes, antioxidant enzymes, metabolic redox enzymes, heat shock proteins, globin hemoproteins, proteins of nitrogen metabolism, and a wide range of viral proteins associated with these endosymbiont-enriched samples. Also present were 21 unusual peptide/protein toxins thought to originate from either microbial consorts or from contamination by coral nematocysts. Of particular interest are the proteins of apoptosis, vesicular transport, and endo/exocytosis, which are discussed in context of the cellular processes of coral bleaching. Notably, the protein complement provides evidence that, rather than being expelled by the host, stressed endosymbionts may mediate their own departure. PMID:22351649

  9. Host-Pathogen Coupled Interactions

    DTIC Science & Technology

    2015-01-04

    AFRL- RH -WP-TP-2015-0012 Host-Pathogen Coupled Interactions Peter J. Robinson C. Eric Hack Jeffery M...them. Qualified requestors may obtain copies of this report from the Defense Technical Information Center (DTIC) (http://www.dtic.mil). (AFRL- RH ...Branch Wright-Patterson AFB OH 45433-5707 10. SPONSOR/MONITOR’S ACRONYM(S) 711 HPW/RHDJ 11. SPONSORING/MONITORING AGENCY REPORT NUMBER AFRL- RH -WP

  10. The genome of the amoeba symbiont "Candidatus Amoebophilus asiaticus" reveals common mechanisms for host cell interaction among amoeba-associated bacteria.

    PubMed

    Schmitz-Esser, Stephan; Tischler, Patrick; Arnold, Roland; Montanaro, Jacqueline; Wagner, Michael; Rattei, Thomas; Horn, Matthias

    2010-02-01

    Protozoa play host for many intracellular bacteria and are important for the adaptation of pathogenic bacteria to eukaryotic cells. We analyzed the genome sequence of "Candidatus Amoebophilus asiaticus," an obligate intracellular amoeba symbiont belonging to the Bacteroidetes. The genome has a size of 1.89 Mbp, encodes 1,557 proteins, and shows massive proliferation of IS elements (24% of all genes), although the genome seems to be evolutionarily relatively stable. The genome does not encode pathways for de novo biosynthesis of cofactors, nucleotides, and almost all amino acids. "Ca. Amoebophilus asiaticus" encodes a variety of proteins with predicted importance for host cell interaction; in particular, an arsenal of proteins with eukaryotic domains, including ankyrin-, TPR/SEL1-, and leucine-rich repeats, which is hitherto unmatched among prokaryotes, is remarkable. Unexpectedly, 26 proteins that can interfere with the host ubiquitin system were identified in the genome. These proteins include F- and U-box domain proteins and two ubiquitin-specific proteases of the CA clan C19 family, representing the first prokaryotic members of this protein family. Consequently, interference with the host ubiquitin system is an important host cell interaction mechanism of "Ca. Amoebophilus asiaticus". More generally, we show that the eukaryotic domains identified in "Ca. Amoebophilus asiaticus" are also significantly enriched in the genomes of other amoeba-associated bacteria (including chlamydiae, Legionella pneumophila, Rickettsia bellii, Francisella tularensis, and Mycobacterium avium). This indicates that phylogenetically and ecologically diverse bacteria which thrive inside amoebae exploit common mechanisms for interaction with their hosts, and it provides further evidence for the role of amoebae as training grounds for bacterial pathogens of humans.

  11. Secretomic Analysis of Host-Pathogen Interactions Reveals That Elongation Factor-Tu Is a Potential Adherence Factor of Helicobacter pylori during Pathogenesis.

    PubMed

    Chiu, Kuo-Hsun; Wang, Ling-Hui; Tsai, Tsung-Ting; Lei, Huan-Yao; Liao, Pao-Chi

    2017-01-06

    The secreted proteins of bacteria are usually accompanied by virulence factors, which can cause inflammation and damage host cells. Identifying the secretomes arising from the interactions of bacteria and host cells could therefore increase understanding of the mechanisms during initial pathogenesis. The present study used a host-pathogen coculture system of Helicobacter pylori and monocytes (THP-1 cells) to investigate the secreted proteins associated with initial H. pylori pathogenesis. The secreted proteins from the conditioned media from H. pylori, THP-1 cells, and the coculture were collected and analyzed using SDS-PAGE and LC-MS/MS. Results indicated the presence of 15 overexpressed bands in the coculture. Thirty-one proteins were identified-11 were derived from THP-1 cells and 20 were derived from H. pylori. A potential adherence factor from H. pylori, elongation factor-Tu (EF-Tu), was selected for investigation of its biological function. Results from confocal microscopic and flow cytometric analyses indicated the contribution of EF-Tu to the binding ability of H. pylori in THP-1. The data demonstrated that fluorescence of EF-Tu on THP-1 cells increased after the addition of the H. pylori-conditioned medium. This study reports a novel secretory adherence factor in H. pylori, EF-Tu, and further elucidates mechanisms of H. pylori adaptation for host-pathogen interaction during pathogenesis.

  12. Genome sequence reveals that Pseudomonas fluorescens F113 possesses a large and diverse array of systems for rhizosphere function and host interaction

    PubMed Central

    2013-01-01

    Background Pseudomonas fluorescens F113 is a plant growth-promoting rhizobacterium (PGPR) isolated from the sugar-beet rhizosphere. This bacterium has been extensively studied as a model strain for genetic regulation of secondary metabolite production in P. fluorescens, as a candidate biocontrol agent against phytopathogens, and as a heterologous host for expression of genes with biotechnological application. The F113 genome sequence and annotation has been recently reported. Results Comparative analysis of 50 genome sequences of strains belonging to the P. fluorescens group has revealed the existence of five distinct subgroups. F113 belongs to subgroup I, which is mostly composed of strains classified as P. brassicacearum. The core genome of these five strains is highly conserved and represents approximately 76% of the protein-coding genes in any given genome. Despite this strong conservation, F113 also contains a large number of unique protein-coding genes that encode traits potentially involved in the rhizocompetence of this strain. These features include protein coding genes required for denitrification, diterpenoids catabolism, motility and chemotaxis, protein secretion and production of antimicrobial compounds and insect toxins. Conclusions The genome of P. fluorescens F113 is composed of numerous protein-coding genes, not usually found together in previously sequenced genomes, which are potentially decisive during the colonisation of the rhizosphere and/or interaction with other soil organisms. This includes genes encoding proteins involved in the production of a second flagellar apparatus, the use of abietic acid as a growth substrate, the complete denitrification pathway, the possible production of a macrolide antibiotic and the assembly of multiple protein secretion systems. PMID:23350846

  13. Host-microorganism interactions in lung diseases.

    PubMed

    Marsland, Benjamin J; Gollwitzer, Eva S

    2014-12-01

    Until recently, the airways were thought to be sterile unless infected; however, a shift towards molecular methods for the quantification and sequencing of bacterial DNA has revealed that the airways harbour a unique steady-state microbiota. This paradigm shift is changing the way that respiratory research is approached, with a clear need now to consider the effects of host-microorganism interactions in both healthy and diseased lungs. We propose that akin to recent discoveries in intestinal research, dysbiosis of the airway microbiota could underlie susceptibility to, and progression and chronicity of lung disease. In this Opinion article, we summarize current knowledge of the airway microbiota and outline how host-microorganism interactions in the lungs and other tissues might influence respiratory health and disease.

  14. RNA-Sequencing Reveals the Progression of Phage-Host Interactions between φR1-37 and Yersinia enterocolitica.

    PubMed

    Leskinen, Katarzyna; Blasdel, Bob G; Lavigne, Rob; Skurnik, Mikael

    2016-04-22

    Despite the expanding interest in bacterial viruses (bacteriophages), insights into the intracellular development of bacteriophage and its impact on bacterial physiology are still scarce. Here we investigate during lytic infection the whole-genome transcription of the giant phage vB_YecM_φR1-37 (φR1-37) and its host, the gastroenteritis causing bacterium Yersinia enterocolitica. RNA sequencing reveals that the gene expression of φR1-37 does not follow a pattern typical observed in other lytic bacteriophages, as only selected genes could be classified as typically early, middle or late genes. The majority of the genes appear to be expressed constitutively throughout infection. Additionally, our study demonstrates that transcription occurs mainly from the positive strand, while the negative strand encodes only genes with low to medium expression levels. Interestingly, we also detected the presence of antisense RNA species, as well as one non-coding intragenic RNA species. Gene expression in the phage-infected cell is characterized by the broad replacement of host transcripts with phage transcripts. However, the host response in the late phase of infection was also characterized by up-regulation of several specific bacterial gene products known to be involved in stress response and membrane stability, including the Cpx pathway regulators, ATP-binding cassette (ABC) transporters, phage- and cold-shock proteins.

  15. RNA-Sequencing Reveals the Progression of Phage-Host Interactions between φR1-37 and Yersinia enterocolitica

    PubMed Central

    Leskinen, Katarzyna; Blasdel, Bob G.; Lavigne, Rob; Skurnik, Mikael

    2016-01-01

    Despite the expanding interest in bacterial viruses (bacteriophages), insights into the intracellular development of bacteriophage and its impact on bacterial physiology are still scarce. Here we investigate during lytic infection the whole-genome transcription of the giant phage vB_YecM_φR1-37 (φR1-37) and its host, the gastroenteritis causing bacterium Yersinia enterocolitica. RNA sequencing reveals that the gene expression of φR1-37 does not follow a pattern typical observed in other lytic bacteriophages, as only selected genes could be classified as typically early, middle or late genes. The majority of the genes appear to be expressed constitutively throughout infection. Additionally, our study demonstrates that transcription occurs mainly from the positive strand, while the negative strand encodes only genes with low to medium expression levels. Interestingly, we also detected the presence of antisense RNA species, as well as one non-coding intragenic RNA species. Gene expression in the phage-infected cell is characterized by the broad replacement of host transcripts with phage transcripts. However, the host response in the late phase of infection was also characterized by up-regulation of several specific bacterial gene products known to be involved in stress response and membrane stability, including the Cpx pathway regulators, ATP-binding cassette (ABC) transporters, phage- and cold-shock proteins. PMID:27110815

  16. Docking studies and network analyses reveal capacity of compounds from Kandelia rheedii to strengthen cellular immunity by interacting with host proteins during tuberculosis infection

    PubMed Central

    Zaman, Aubhishek

    2012-01-01

    Kandelia rheedii (locally known as Guria or Rasunia), widely found and used in Indian subcontinent, is a well-known herbal cure to tuberculosis. However, neither the mechanism nor the active components of the plant extract responsible for mediating this action has yet been confirmed. Here in this study, molecular interactions of three compounds (emodin, fusaric acid and skyrin) from the plant extract with the host protein targets (casein kinase (CSNK), estrogen receptor (ERBB), dopamine β-hydroxylase (DBH) and glucagon receptor (Gcgr)) has been found. These protein targets are known to be responsible for strengthening cellular immunity against Mycobacteria tuberculosis. The specific interactions of these three compounds with the respective protein targets have been discussed here. The insights from study should further help us designing molecular medicines against tuberculosis. PMID:23275699

  17. Molecular analysis of the early interaction between the grapevine flower and Botrytis cinerea reveals that prompt activation of specific host pathways leads to fungus quiescence.

    PubMed

    Mehari, Zeraye H; Pilati, Stefania; Sonego, Paolo; Malacarne, Giulia; Vrhovsek, Urska; Engelen, Kristof; Tudzynski, Paul; Zottini, Michela; Baraldi, Elena; Moser, Claudio

    2017-02-27

    Grapes quality and yield can be impaired by bunch rot, caused by the necrotrophic fungus Botrytis cinerea. Infection often occurs at flowering and the pathogen stays quiescent until fruit maturity. Here, we report a molecular analysis of the early interaction between B. cinerea and Vitis vinifera flowers, using a controlled infection system, confocal microscopy and integrated transcriptomic and metabolic analysis of the host and the pathogen. Flowers from fruiting cuttings of the cv. Pinot Noir were infected with GFP-labeled B. cinerea and studied at 24 and 96 hours post inoculation (hpi). We observed that penetration of the epidermis by B. cinerea coincided with increased expression of genes encoding cell wall-degrading enzymes, phytotoxins, and proteases. Grapevine responded with a rapid defense reaction involving 1193 genes associated with the accumulation of antimicrobial proteins, polyphenols, reactive oxygen species and cell wall reinforcement. At 96 hpi the reaction appears largely diminished both in the host and in the pathogen. Our data indicate that the defense responses of the grapevine flower collectively are able to restrict invasive fungal growth into the underlying tissues, thereby forcing the fungus to enter quiescence until the conditions become more favorable to resume pathogenic development.

  18. Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions

    SciTech Connect

    Lin, David Yin-wei; Diao, Jianbo; Chen, Jue

    2012-12-10

    In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial 'Trojan horses' integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s, Salmonella SopA and Escherichia coli NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleL has little similarity to those of eukaryotic E3s. However, both bacterial E3s bind to the canonical surface of E2 that normally interacts with eukaryotic E3s. Furthermore, we show that a glutamate residue on E3 is involved in catalyzing ubiquitin transfer from E3 to the substrate, but not from E2 to E3. Together, these results provide mechanistic insights into the ubiquitin pathway and a framework for understanding molecular mimicry in bacterial pathogenesis.

  19. Salmonellae interactions with host processes.

    PubMed

    LaRock, Doris L; Chaudhary, Anu; Miller, Samuel I

    2015-04-01

    Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms that salmonellae use to alter host cell physiology; through the delivery of effector proteins with specific activities and through the modulation of defence and stress response pathways. In this Review, we summarize our current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts, with a particular focus on Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps in our knowledge of the contributions of salmonellae and the host to disease pathogenesis, and we suggest future avenues for further study.

  20. Host-gut microbiota metabolic interactions.

    PubMed

    Nicholson, Jeremy K; Holmes, Elaine; Kinross, James; Burcelin, Remy; Gibson, Glenn; Jia, Wei; Pettersson, Sven

    2012-06-08

    The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.

  1. Integrated inference and evaluation of host-fungi interaction networks.

    PubMed

    Remmele, Christian W; Luther, Christian H; Balkenhol, Johannes; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus T

    2015-01-01

    Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host-pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host-fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen-host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi-human and fungi-mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host-fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host-fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host-fungi transcriptome and proteome data.

  2. Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology

    PubMed Central

    DeBlasio, Stacy L.; Chavez, Juan D.; Alexander, Mariko M.; Ramsey, John; Eng, Jimmy K.; Mahoney, Jaclyn; Gray, Stewart M.; Bruce, James E.

    2015-01-01

    ABSTRACT Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus [PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in the Luteoviridae and with unrelated viruses in the Herpesviridae and Adenoviridae. Functional analysis of three PLRV-interacting host proteins in planta using a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection—hallmarks of host-pathogen interactions—were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies. IMPORTANCE The exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used

  3. Revealing Non-Covalent Interactions

    PubMed Central

    Johnson, Erin R.; Keinan, Shahar; Mori-Sánchez, Paula; Contreras-García, Julia; Cohen, Aron J.; Yang, Weitao

    2010-01-01

    Molecular structure does not easily identify the intricate non-covalent interactions that govern many areas of biology and chemistry, including design of new materials and drugs. We develop an approach to detect non-covalent interactions in real space, based on the electron density and its derivatives. Our approach reveals underlying chemistry that compliments the covalent structure. It provides a rich representation of van der Waals interactions, hydrogen bonds, and steric repulsion in small molecules, molecular complexes, and solids. Most importantly, the method, requiring only knowledge of the atomic coordinates, is efficient and applicable to large systems, such as proteins or DNA. Across these applications, a view of non-bonded interactions emerges as continuous surfaces rather than close contacts between atom pairs, offering rich insight into the design of new and improved ligands. PMID:20394428

  4. Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions

    PubMed Central

    Ruiz, Lorena; Delgado, Susana; Ruas-Madiedo, Patricia; Margolles, Abelardo; Sánchez, Borja

    2016-01-01

    Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs. PMID:27536282

  5. Probing Pseudomonas syringae host interactions using metatranscriptomics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transcriptome analyses during the interaction of plants and pathogens can be used to provide insights into molecular mechanisms of plant resistance as well as the mechanisms used by bacteria to adapt to hosts and cause disease. We performed a dual in planta RNA-Seq experiment to profile RNA expressi...

  6. Label-free Proteomic Reveals that Cowpea Severe Mosaic Virus Transiently Suppresses the Host Leaf Protein Accumulation During the Compatible Interaction with Cowpea (Vigna unguiculata [L.] Walp.).

    PubMed

    Paiva, Ana L S; Oliveira, Jose T A; de Souza, Gustavo A; Vasconcelos, Ilka M

    2016-12-02

    Viruses are important plant pathogens that threaten diverse crops worldwide. Diseases caused by Cowpea severe mosaic virus (CPSMV) have drawn attention because of the serious damages they cause to economically important crops including cowpea. This work was undertaken to quantify and identify the responsive proteins of a susceptible cowpea genotype infected with CPSMV, in comparison with mock-inoculated controls, using label-free quantitative proteomics and databanks, aiming at providing insights on the molecular basis of this compatible interaction. Cowpea leaves were mock- or CPSMV-inoculated and 2 and 6 days later proteins were extracted and analyzed. More than 3000 proteins were identified (data available via ProteomeXchange, identifier PXD005025) and 75 and 55 of them differentially accumulated in response to CPSMV, at 2 and 6 DAI, respectively. At 2 DAI, 76% of the proteins decreased in amount and 24% increased. However, at 6 DAI, 100% of the identified proteins increased. Thus, CPSMV transiently suppresses the synthesis of proteins involved particularly in the redox homeostasis, protein synthesis, defense, stress, RNA/DNA metabolism, signaling, and other functions, allowing viral invasion and spread in cowpea tissues.

  7. Interactions between hemiparasitic plants and their hosts

    PubMed Central

    Plavcová, Lenka; Cameron, Duncan D

    2010-01-01

    Hemiparasitic plants display a unique strategy of resource acquisition combining parasitism of other species and own photosynthetic activity. Despite the active photoassimilation and green habit, they acquire substantial amount of carbon from their hosts. The organic carbon transfer has a crucial influence on the nature of the interaction between hemiparasites and their hosts which can oscillate between parasitism and competition for light. In this minireview, we summarize methodical approaches and results of various studies dealing with carbon budget of hemiparasites and the ecological implications of carbon heterotrophy in hemiparasites. PMID:20729638

  8. Statistical structure of host-phage interactions.

    PubMed

    Flores, Cesar O; Meyer, Justin R; Valverde, Sergi; Farr, Lauren; Weitz, Joshua S

    2011-07-12

    Interactions between bacteria and the viruses that infect them (i.e., phages) have profound effects on biological processes, but despite their importance, little is known on the general structure of infection and resistance between most phages and bacteria. For example, are bacteria-phage communities characterized by complex patterns of overlapping exploitation networks, do they conform to a more ordered general pattern across all communities, or are they idiosyncratic and hard to predict from one ecosystem to the next? To answer these questions, we collect and present a detailed metaanalysis of 38 laboratory-verified studies of host-phage interactions representing almost 12,000 distinct experimental infection assays across a broad spectrum of taxa, habitat, and mode of selection. In so doing, we present evidence that currently available host-phage infection networks are statistically different from random networks and that they possess a characteristic nested structure. This nested structure is typified by the finding that hard to infect bacteria are infected by generalist phages (and not specialist phages) and that easy to infect bacteria are infected by generalist and specialist phages. Moreover, we find that currently available host-phage infection networks do not typically possess a modular structure. We explore possible underlying mechanisms and significance of the observed nested host-phage interaction structure. In addition, given that most of the available host-phage infection networks examined here are composed of taxa separated by short phylogenetic distances, we propose that the lack of modularity is a scale-dependent effect, and then, we describe experimental studies to test whether modular patterns exist at macroevolutionary scales.

  9. Systems analysis of host-parasite interactions.

    PubMed

    Swann, Justine; Jamshidi, Neema; Lewis, Nathan E; Winzeler, Elizabeth A

    2015-01-01

    Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies.

  10. Host interactions of Chandipura virus matrix protein.

    PubMed

    Rajasekharan, Sreejith; Kumar, Kapila; Rana, Jyoti; Gupta, Amita; Chaudhary, Vijay K; Gupta, Sanjay

    2015-09-01

    The rhabdovirus matrix (M) protein is a multifunctional virion protein that plays major role in virus assembly and budding, virus-induced inhibition of host gene expression and cytopathic effects observed in infected cells. The myriad roles played by this protein in the virus biology make it a critical player in viral pathogenesis. Therefore, discerning the interactions of this protein with host can greatly facilitate our understanding of virus infections, ultimately leading to both improved therapeutics and insight into cellular processes. Chandipura virus (CHPV; Family Rhabdoviridae, Genus Vesiculovirus) is an emerging rhabdovirus responsible for several outbreaks of fatal encephalitis among children in India. The present study aims to screen the human fetal brain cDNA library for interactors of CHPV M protein using yeast two-hybrid system. Ten host protein interactors were identified, three of which were further validated by affinity pull down and protein interaction ELISA. The study identified novel human host interactors for CHPV which concurred with previously described associations in other human viruses.

  11. Interactions of Bacterial Proteins with Host Eukaryotic Ubiquitin Pathways

    PubMed Central

    Perrett, Charlotte Averil; Lin, David Yin-Wei; Zhou, Daoguo

    2011-01-01

    Ubiquitination is a post-translational modification in which one or more 76 amino acid polypeptide ubiquitin molecules are covalently linked to the lysine residues of target proteins. Ubiquitination is the main pathway for protein degradation that governs a variety of eukaryotic cellular processes, including the cell-cycle, vesicle trafficking, antigen presentation, and signal transduction. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of many diseases including inflammatory and neurodegenerative disorders. Recent studies have revealed that viruses and bacterial pathogens exploit the host ubiquitination pathways to gain entry and to aid their survival/replication inside host cells. This review will summarize recent developments in understanding the biochemical and structural mechanisms utilized by bacterial pathogens to interact with the host ubiquitination pathways. PMID:21772834

  12. HIV–host interactome revealed directly from infected cells

    PubMed Central

    Luo, Yang; Jacobs, Erica Y.; Greco, Todd M.; Mohammed, Kevin D.; Tong, Tommy; Keegan, Sarah; Binley, James M.; Cristea, Ileana M.; Fenyö, David; Rout, Michael P.; Chait, Brian T.; Muesing, Mark A.

    2016-01-01

    Although genetically compact, HIV-1 commandeers vast arrays of cellular machinery to sustain and protect it during cycles of viral outgrowth. Transposon-mediated saturation linker scanning mutagenesis was used to isolate fully replication-competent viruses harbouring a potent foreign epitope tag. Using these viral isolates, we performed differential isotopic labelling and affinity-capture mass spectrometric analyses on samples obtained from cultures of human lymphocytes to classify the vicinal interactomes of the viral Env and Vif proteins as they occur during natural infection. Importantly, interacting proteins were recovered without bias, regardless of their potential for positive, negative or neutral impact on viral replication. We identified specific host associations made with trimerized Env during its biosynthesis, at virological synapses, with innate immune effectors (such as HLA-E) and with certain cellular signalling pathways (for example, Notch1). We also defined Vif associations with host proteins involved in the control of nuclear transcription and nucleoside biosynthesis as well as those interacting stably or transiently with the cytoplasmic protein degradation apparatus. Our approach is broadly applicable to elucidating pathogen–host interactomes, providing high-certainty identification of interactors by their direct access during cycling infection. Understanding the pathophysiological consequences of these associations is likely to provide strategic targets for antiviral intervention. PMID:27375898

  13. Host-to-host variation of ecological interactions in polymicrobial infections

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sayak; Weimer, Kristin E.; Seok, Sang-Cheol; Ray, Will C.; Jayaprakash, C.; Vieland, Veronica J.; Swords, W. Edward; Das, Jayajit

    2015-02-01

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species.

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

    PubMed

    Samaddar, Sourabh; Grewal, Rajdeep Kaur; Sinha, Saptarshi; Ghosh, Shrestha; Roy, Soumen; Das Gupta, Sujoy K

    2015-10-16

    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.

  15. Macrophage Polarization in Virus-Host Interactions

    PubMed Central

    Sang, Yongming; Miller, Laura C; Blecha, Frank

    2015-01-01

    Macrophage involvement in viral infections and antiviral states is common. However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses. Recent studies have revealed the complexity of macrophage polarization in response to various cellular mediators and exogenous stimuli by adopting a multipolar view to revisit the differential process of macrophages, especially those re-polarized during viral infections. Here, through examination of viral infections targeting macrophages/monocytic cells, we focus on the direct involvement of macrophage polarization during viral infections. Type I and type III interferons (IFNs) are critical in regulation of viral pathogenesis and host antiviral infection; thus, we propose to incorporate IFN-mediated antiviral states into the framework of macrophage polarization. This view is supported by the multifunctional properties of type I IFNs, which potentially elicit and regulate both M1- and M2-polarization in addition to inducing the antiviral state, and by the discoveries of viral mechanisms to adapt and modulate macrophage polarization. Indeed, several recent studies have demonstrated effective prevention of viral diseases through manipulation of macrophage immune statuses. PMID:26213635

  16. Host-Parasite Interactions in Some Fish Species

    PubMed Central

    Khan, R. A.

    2012-01-01

    Host-parasite interactions are complex, compounded by factors that are capable of shifting the balance in either direction. The host's age, behaviour, immunological status, and environmental change can affect the association that is beneficial to the host whereas evasion of the host's immune response favours the parasite. In fish, some infections that induce mortality are age and temperature dependent. Environmental change, especially habitat degradation by anthropogenic pollutants and oceanographic alterations induced by climatic, can influence parasitic-host interaction. The outcome of these associations will hinge on susceptibility and resistance. PMID:22900144

  17. Host-microbe interactions in the developing zebrafish

    PubMed Central

    Kanther, Michelle; Rawls, John F.

    2010-01-01

    Summary of recent advances The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular foundations of host-microbe relationships. Study of microbial encounters in zebrafish hosts has concentrated on developing embryonic and larval stages, when the advantages of the zebrafish model are maximized. A comprehensive understanding of these host-microbe interactions requires appreciation of the developmental context into which a microbe is introduced, as well as the effects of that microbial challenge on host ontogeny. In this review, we discuss how in vivo imaging and genetic analysis in zebrafish has advanced our knowledge of host-microbe interactions in the context of a developing vertebrate host. We focus on recent insights into immune cell ontogeny and function, commensal microbial relationships in the intestine, and microbial pathogenesis in zebrafish hosts. PMID:20153622

  18. Displaced tick-parasite interactions at the host interface.

    PubMed

    Nuttall, P A

    1998-01-01

    Reciprocal interactions of parasites transmitted by blood-sucking arthropod vectors have been studied primarily at the parasite-host and parasite-vector interface. The third component of this parasite triangle, the vector-host interface, has been largely ignored. Now there is growing realization that reciprocal interactions between arthropod vectors and their vertebrate hosts play a pivotal role in the survival of arthropod-borne viruses, bacteria, and protozoa. The vector-host interface is the site where the haematophagous arthropods feeds. To obtain a blood meal, the vector must overcome the host's inflammatory, haemostatic, and immune responses. This problem is greatest for ixodid ticks which may imbibe as much as 15 ml blood whilst continuously attached to their host for 10 days or more. To feed successfully, the interface between tick and host becomes a battle between the host's mechanisms for combating the tick and the tick's armoury of bioactive proteins and other chemicals which it secrets, via saliva, into the feeding lesion formed in the host's skin. Parasites entering this battlefield encounter a privileged site in their vertebrate host that has been profoundly modified by the pharmacological activities of their vector's saliva. For example, ticks suppress natural killer cells and interferons, both of which have potent antiviral activities. Not surprisingly, vector-bone parasites exploit the immunomodulated feeding site to promote their transmission and infection. Certain tick-bone viruses are so successful at this that they are transmitted from one infected tick, through the vertebrate host to a co-feeding uninfected tick, without a detectable viraemia (virus circulating in the host's blood), and with no untoward effect on the host. When such viruses do have an adverse effect on the host, they may impede their vectors' feeding. Thus important interactions between ticks and tick-borne parasites are displaced to the interface with their vertebrate host

  19. Biological warfare: Microorganisms as drivers of host-parasite interactions.

    PubMed

    Dheilly, Nolwenn M; Poulin, Robert; Thomas, Frédéric

    2015-08-01

    Understanding parasite strategies for evasion, manipulation or exploitation of hosts is crucial for many fields, from ecology to medical sciences. Generally, research has focused on either the host response to parasitic infection, or the parasite virulence mechanisms. More recently, integrated studies of host-parasite interactions have allowed significant advances in theoretical and applied biology. However, these studies still provide a simplistic view of these as mere two-player interactions. Host and parasite are associated with a myriad of microorganisms that could benefit from the improved fitness of their partner. Illustrations of such complex multi-player interactions have emerged recently from studies performed in various taxa. In this conceptual article, we propose how these associated microorganisms may participate in the phenotypic alterations induced by parasites and hence in host-parasite interactions, from an ecological and evolutionary perspective. Host- and parasite-associated microorganisms may participate in the host-parasite interaction by interacting directly or indirectly with the other partner. As a result, parasites may develop (i) the disruptive strategy in which the parasite alters the host microbiota to its advantage, and (ii) the biological weapon strategy where the parasite-associated microorganism contributes to or modulates the parasite's virulence. Some phenotypic alterations induced by parasite may also arise from conflicts of interests between the host or parasite and its associated microorganism. For each situation, we review the literature and propose new directions for future research. Specifically, investigating the role of host- and parasite-associated microorganisms in host-parasite interactions at the individual, local and regional level will lead to a holistic understanding of how the co-evolution of the different partners influences how the other ones respond, both ecologically and evolutionary. The conceptual framework we

  20. Microfluidic large scale integration of viral-host interaction analysis.

    PubMed

    Ben-Ari, Ya'ara; Glick, Yair; Kipper, Sarit; Schwartz, Nika; Avrahami, Dorit; Barbiro-Michaely, Efrat; Gerber, Doron

    2013-06-21

    Viral-host interactions represent potential drug targets for novel antiviral strategies (Flisiak et al., Hepatology, 2008, 47, 817-26). Hence, it is important to establish an adequate platform for identifying and analyzing such interactions. In this review, we discuss bottlenecks in conventional protein-protein interaction methodologies and present the contribution of innovative microfluidic-based technologies towards a solution to these problems with respect to viral-host proteomics.

  1. Citrus tristeza virus-host interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrus tristeza virus (CTV) is a phloem-limited virus whose natural host range is restricted to citrus and related species. Although the virus has killed millions of trees, almost destroying whole industries, and continually limits production in many citrus growing areas, most isolates are mild or s...

  2. Host-Opportunist Interactions in Surgical Infection

    DTIC Science & Technology

    1986-01-01

    assertions contained herein are the private views of the poses to fungal infection~as well as wound temperature and author and are not to be construed as...exaggeration Tvedten et al," showing a protective effect of catalase or thereof may be observed.𔄂 14 Arch Surg-Vol 121, Jan 1986 C Host-Opportunist...Life-threatening infections, particu- identification of bacterial, fungal , and viral wound infec- larly those caused by gram-negative organisms, are

  3. Host-pathogen interactions: A cholera surveillance system

    SciTech Connect

    Wright, Aaron T.

    2016-02-22

    Bacterial pathogen-secreted proteases may play a key role in inhibiting a potentially widespread host-pathogen interaction. Activity-based protein profiling enabled the identification of a major Vibrio cholerae serine protease that limits the ability of a host-derived intestinal lectin to bind to the bacterial pathogen in vivo.

  4. A chemical arms race at sea mediates algal host-virus interactions.

    PubMed

    Bidle, Kay D; Vardi, Assaf

    2011-08-01

    Despite the critical importance of viruses in shaping marine microbial ecosystems and lubricating upper ocean biogeochemical cycles, relatively little is known about the molecular mechanisms mediating phytoplankton host-virus interactions. Recent work in algal host-virus systems has begun to shed novel insight into the elegant strategies of viral infection and subcellular regulation of cell fate, which not only reveal tantalizing aspects of viral replication and host resistance strategies but also provide new diagnostic tools toward elucidating the impact of virus-mediated processes in the ocean. Widespread lateral gene transfer between viruses and their hosts plays a prominent role in host-virus diversification and in the regulation of host-virus infection mechanisms by allowing viruses to manipulate and 'rewire' host metabolic pathways to facilitate infection.

  5. Olfactory regulation of mosquito–host interactions

    PubMed Central

    Zwiebel, L.J.; Takken, W.

    2011-01-01

    Mosquitoes that act as disease vectors rely upon olfactory cues to direct several important behaviors that are fundamentally involved in establishing their overall vectorial capacity. Of these, the propensity to select humans for blood feeding is arguably the most important of these olfactory driven behaviors in so far as it significantly contributes to the ability of these mosquitoes to transmit pathogens that cause diseases such as dengue, yellow fever and most significantly human malaria. Here, we review significant advances in behavioral, physiological and molecular investigations into mosquito host preference, with a particular emphasis on studies that have emerged in the post-genomic era that seek to combine these approaches. PMID:15242705

  6. Architecture and host interface of environmental chlamydiae revealed by electron cryotomography

    PubMed Central

    Pilhofer, Martin; Aistleitner, Karin; Ladinsky, Mark S.; König, Lena; Horn, Matthias; Jensen, Grant J.

    2016-01-01

    Summary Chlamydiae comprise important pathogenic and symbiotic bacteria that alternate between morphologically and physiologically different life stages during their developmental cycle. Using electron cryotomography, we characterize the ultrastructure of the developmental stages of three environmental chlamydiae: Parachlamydia acanthamoebae, Protochlamydia amoebophila and Simkania negevensis. We show that chemical fixation and dehydration alter the cell shape of Parachlamydia and that the crescent body is not a developmental stage, but an artefact of conventional electron microscopy. We further reveal type III secretion systems of environmental chlamydiae at macromolecular resolution and find support for a chlamydial needle-tip protein. Imaging bacteria inside their host cells by cryotomography for the first time, we observe marked differences in inclusion morphology and development as well as host organelle recruitment between the three chlamydial organisms, with Simkania inclusions being tightly enveloped by the host endoplasmic reticulum. The study demonstrates the power of electron cryotomography to reveal structural details of bacteria–host interactions that are not accessible using traditional methods. PMID:24118768

  7. Expanding the antimalarial toolkit: Targeting host-parasite interactions.

    PubMed

    Langhorne, Jean; Duffy, Patrick E

    2016-02-08

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

  8. Functional genomics of a generalist parasitic plant: Laser microdissection of host-parasite interface reveals host-specific patterns of parasite gene expression

    PubMed Central

    2013-01-01

    Background Orobanchaceae is the only plant family with members representing the full range of parasitic lifestyles plus a free-living lineage sister to all parasitic lineages, Lindenbergia. A generalist member of this family, and an important parasitic plant model, Triphysaria versicolor regularly feeds upon a wide range of host plants. Here, we compare de novo assembled transcriptomes generated from laser micro-dissected tissues at the host-parasite interface to uncover details of the largely uncharacterized interaction between parasitic plants and their hosts. Results The interaction of Triphysaria with the distantly related hosts Zea mays and Medicago truncatula reveals dramatic host-specific gene expression patterns. Relative to above ground tissues, gene families are disproportionally represented at the interface including enrichment for transcription factors and genes of unknown function. Quantitative Real-Time PCR of a T. versicolor β-expansin shows strong differential (120x) upregulation in response to the monocot host Z. mays; a result that is concordant with our read count estimates. Pathogenesis-related proteins, other cell wall modifying enzymes, and orthologs of genes with unknown function (annotated as such in sequenced plant genomes) are among the parasite genes highly expressed by T. versicolor at the parasite-host interface. Conclusions Laser capture microdissection makes it possible to sample the small region of cells at the epicenter of parasite host interactions. The results of our analysis suggest that T. versicolor’s generalist strategy involves a reliance on overlapping but distinct gene sets, depending upon the host plant it is parasitizing. The massive upregulation of a T. versicolor β-expansin is suggestive of a mechanism for parasite success on grass hosts. In this preliminary study of the interface transcriptomes, we have shown that T. versicolor, and the Orobanchaceae in general, provide excellent opportunities for the

  9. Exploring NAD+ metabolism in host-pathogen interactions.

    PubMed

    Mesquita, Inês; Varela, Patrícia; Belinha, Ana; Gaifem, Joana; Laforge, Mireille; Vergnes, Baptiste; Estaquier, Jérôme; Silvestre, Ricardo

    2016-03-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.

  10. Host-microbe protein interactions during bacterial infection

    PubMed Central

    Schweppe, Devin K.; Harding, Christopher; Chavez, Juan D.; Wu, Xia; Ramage, Elizabeth; Singh, Pradeep K.; Manoil, Colin; Bruce, James E.

    2015-01-01

    Summary Interspecies protein-protein interactions are essential mediators of infection. While bacterial proteins required for host cell invasion and infection can be identified through bacterial mutant library screens, information about host target proteins and interspecies complex structures has been more difficult to acquire. Using an unbiased chemical cross-linking/mass spectrometry approach, we identified interspecies protein-protein interactions in human lung epithelial cells infected with Acinetobacter baumannii. These efforts resulted in identification of 3076 total cross-linked peptide pairs and 46 interspecies protein-protein interactions. Most notably, the key A. baumannii virulence factor, OmpA, was identified cross-linked to host proteins involved in desmosomes, specialized structures that mediate host cell-to-cell adhesion. Co-immunoprecipitation and transposon mutant experiments were used to verify these interactions and demonstrate relevance for host cell invasion and acute murine lung infection. These results shed new light on A. baumannii-host protein interactions and their structural features and the presented approach is generally applicable to other systems. PMID:26548613

  11. Macrophage polarization in virus-host interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macrophage involvement in viral infections and antiviral states is common. However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses. Recent studies have reveal...

  12. Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease.

    PubMed

    Erickson, Alison R; Cantarel, Brandi L; Lamendella, Regina; Darzi, Youssef; Mongodin, Emmanuel F; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C; Fraser, Claire M; Hettich, Robert L; Jansson, Janet K

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  13. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

    PubMed Central

    Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

  14. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

    SciTech Connect

    Erickson, Alison L; Cantarel, Brandi; Lamendella, Regina; Darzi, Youssef; Mongodin, Emmanuel; Pan, Chongle; Shah, Manesh B; Halfvarsson, J; Tysk, C; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C; Fraser-Liggett, C; Hettich, Robert {Bob} L; Jansson, Janet

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  15. Competitive interactions between parasitoids provide new insight into host suppression.

    PubMed

    Xu, Hai-Yun; Yang, Nian-Wan; Wan, Fang-Hao

    2013-01-01

    Understanding the dynamics of potential inter- and intraspecific competition in parasitoid communities is crucial in the screening of efficient parasitoid species and for utilization of the best parasitoid species combinations. In this respect, the host-parasitoid systems, Bemisia tabaci and two parasitoids, Eretmocerus hayati (exotic) and Encarsia sophia (existing) were studied under laboratory conditions to investigate whether interference competition between the exotic and existing species occurs as well as the influence of potential interference competition on the suppression of the host B. tabaci. Studies on interspecific-, intraspecific- and self-interference competition in two parasitoid species were conducted under both rich and limited host resource conditions. Results showed that (1) both parasitoid species negatively affect the progeny production of the other under both rich and limited host resource conditions; (2) both parasitoid species interfered intraspecifically on conspecific parasitized hosts when the available hosts are scarce and; 3) the mortality of B. tabaci induced by parasitoids via parasitism, host-feeding or both parasitism and host-feeding together varied among treatments under different host resource conditions, but showed promise for optimizing control strategies. As a result of our current findings, we suggest a need to investigate the interactions between the two parasitoids on continuous generations.

  16. Eimeria bovis: an update on parasite-host cell interactions.

    PubMed

    Hermosilla, Carlos; Ruiz, Antonio; Taubert, Anja

    2012-10-01

    Apicomplexan parasites are obligate intracellular protozoans and are well recognized modulators of the host cell machinery on varying levels such as host cell metabolism, MHC expression, cell cycle, or apoptosis in order to guarantee their intracellular development and survival. One of the most thoroughly examined apicomplexan pathogens demonstrating a potent manipulative capacity with respect to various host cell functions is Toxoplasma gondii, a protozoon exhibiting rapid intracellular development with small meronts in any nucleated cell, almost irrespective of the cell type or host origin. In contrast, Eimeria bovis merogony I is host- and cell type-restricted and occurs exclusively in bovine endothelial host cells. Furthermore, as a peculiarity, intracellular E. bovis meront I development is a long-lasting process (up to 3 weeks), leading to the formation of huge macromeronts of up to 300 μm in size, containing up to 120,000 merozoites I as offspring. In consequence, the necessity for intense host cell modulation to support this particular development appears even more pressing than in other apicomplexan parasite cases. Here we review the data currently available on E. bovis-host cell interactions, indicating the intriguing capacity of this protozoan to exploit and utilize its host cell for its own benefit.

  17. Within-host competition between Borrelia afzelii ospC strains in wild hosts as revealed by massively parallel amplicon sequencing.

    PubMed

    Strandh, Maria; Råberg, Lars

    2015-08-19

    Infections frequently consist of more than one strain of a given pathogen. Experiments have shown that co-infecting strains often compete, so that the infection intensity of each strain in mixed infections is lower than in single strain infections. Such within-host competition can have important epidemiological and evolutionary consequences. However, the extent of competition has rarely been investigated in wild, naturally infected hosts, where there is noise in the form of varying inoculation doses, asynchronous infections and host heterogeneity, which can potentially alleviate or eliminate competition. Here, we investigated the extent of competition between Borrelia afzelii strains (as determined by ospC genotype) in three host species sampled in the wild. For this purpose, we developed a protocol for 454 amplicon sequencing of ospC, which allows both detection and quantification of each individual strain in an infection. Each host individual was infected with one to six ospC strains. The infection intensity of each strain was lower in mixed infections than in single ones, showing that there was competition. Rank-abundance plots revealed that there was typically one dominant strain, but that the evenness of the relative infection intensity of the different strains in an infection increased with the multiplicity of infection. We conclude that within-host competition can play an important role under natural conditions despite many potential sources of noise, and that quantification by next-generation amplicon sequencing offers new possibilities to dissect within-host interactions in naturally infected hosts.

  18. Interaction of chlamydiae and host cells in vitro.

    PubMed Central

    Moulder, J W

    1991-01-01

    The obligately intracellular bacteria of the genus Chlamydia, which is only remotely related to other eubacterial genera, cause many diseases of humans, nonhuman mammals, and birds. Interaction of chlamydiae with host cells in vitro has been studied as a model of infection in natural hosts and as an example of the adaptation of an organism to an unusual environment, the inside of another living cell. Among the novel adaptations made by chlamydiae have been the substitution of disulfide-bond-cross-linked polypeptides for peptidoglycans and the use of host-generated nucleotide triphosphates as sources of metabolic energy. The effect of contact between chlamydiae and host cells in culture varies from no effect at all to rapid destruction of either chlamydiae or host cells. When successful infection occurs, it is usually followed by production of large numbers of progeny and destruction of host cells. However, host cells containing chlamydiae sometimes continue to divide, with or without overt signs of infection, and chlamydiae may persist indefinitely in cell cultures. Some of the many factors that influence the outcome of chlamydia-host cell interaction are kind of chlamydiae, kind of host cells, mode of chlamydial entry, nutritional adequacy of the culture medium, presence of antimicrobial agents, and presence of immune cells and soluble immune factors. General characteristics of chlamydial multiplication in cells of their natural hosts are reproduced in established cell lines, but reproduction in vitro of the subtle differences in chlamydial behavior responsible for the individuality of the different chlamydial diseases will require better in vitro models. PMID:2030670

  19. First in Vivo Batrachochytrium dendrobatidis Transcriptomes Reveal Mechanisms of Host Exploitation, Host-Specific Gene Expression, and Expressed Genotype Shifts

    PubMed Central

    Ellison, Amy R.; DiRenzo, Graziella V.; McDonald, Caitlin A.; Lips, Karen R.; Zamudio, Kelly R.

    2016-01-01

    For generalist pathogens, host species represent distinct selective environments, providing unique challenges for resource acquisition and defense from host immunity, potentially resulting in host-dependent differences in pathogen fitness. Gene expression modulation should be advantageous, responding optimally to a given host and mitigating the costs of generalism. Batrachochytrium dendrobatidis (Bd), a fungal pathogen of amphibians, shows variability in pathogenicity among isolates, and within-strain virulence changes rapidly during serial passages through artificial culture. For the first time, we characterize the transcriptomic profile of Bd in vivo, using laser-capture microdissection. Comparison of Bd transcriptomes (strain JEL423) in culture and in two hosts (Atelopus zeteki and Hylomantis lemur), reveals >2000 differentially expressed genes that likely include key Bd defense and host exploitation mechanisms. Variation in Bd transcriptomes from different amphibian hosts demonstrates shifts in pathogen resource allocation. Furthermore, expressed genotype variant frequencies of Bd populations differ between culture and amphibian skin, and among host species, revealing potential mechanisms underlying rapid changes in virulence and the possibility that amphibian community composition shapes Bd evolutionary trajectories. Our results provide new insights into how changes in gene expression and infecting population genotypes can be key to the success of a generalist fungal pathogen. PMID:27856699

  20. Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication

    PubMed Central

    Wu, Kan Xing; Phuektes, Patchara; Kumar, Pankaj; Goh, Germaine Yen Lin; Moreau, Dimitri; Chow, Vincent Tak Kwong; Bard, Frederic; Chu, Justin Jang Hann

    2016-01-01

    Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation. We demonstrate nuclear egress of CDK6 in EV71 infected cells, and identify CDK6 and AURKB as resistance factors. NGLY1, which co-localizes with EV71 replication complexes at the endoplasmatic reticulum, supports EV71 replication. We confirm importance of these factors for EV71 replication in a human neuronal cell line and for coxsackievirus A16 infection. A small molecule inhibitor of NGLY1 reduces EV71 replication. This study provides a comprehensive map of EV71 host factors and reveals potential antiviral targets. PMID:27748395

  1. Transcriptional changes in Giardia during host-parasite interactions.

    PubMed

    Ringqvist, Emma; Avesson, Lotta; Söderbom, Fredrik; Svärd, Staffan G

    2011-03-01

    Giardia intestinalis is one of the major causes of parasite-induced diarrhea. The disease, giardiasis, is caused by trophozoites attaching to the intestinal epithelium, resulting in apoptosis of intestinal epithelial cells, disrupted epithelial barrier function and malabsorption. Microarray studies have detected extensive gene expression changes in intestinal epithelial cells (IECs) during interaction with Giardia trophozoites in vitro. In the present study, we examined this host-parasite interaction further by transcriptional profiling of interacting trophozoites using Giardia microarrays. A total of 200 Giardia transcripts were significantly changed due to the interaction, lasting up to 18 h in complete growth medium. Quantitative reverse transcriptase PCR confirmed the changes in all 12 genes tested using mRNA isolated in separate experiments. Genes encoding proteins previously suggested to be important during host-parasite interactions such as arginine deiminase, enolase and cysteine proteinases were up-regulated early but down-regulated later during the interaction. Cell division and attachment genes were down-regulated in the late time-points of interaction. The most highly up-regulated genes encode oxygen defense proteins and several members of the high cysteine membrane protein (HCMp) and Gly-rich repeat (GRREAT) families. Putative small RNAs were up-regulated, whereas the 5S rRNA was slightly down-regulated during the interaction with IECs. Thus, there are extensive gene expression changes in Giardia trophozoites and IECs during host-parasite interactions which can be important for establishment of infection and the induction of giardiasis.

  2. Studies of host graft interactions in vitro

    NASA Astrophysics Data System (ADS)

    Liljekvist-Larsson, Ingela; Johansson, Kjell

    2007-09-01

    Progenitor and stem cell transplantation represent therapeutic strategies for retinal disorders that are accompanied by photoreceptor degeneration. The transplanted cells may either replace degenerating photoreceptors or secrete beneficial factors that halt the processes of photoreceptor degeneration. The present study analyzes whether rat retinal progenitor cells differentiated into photoreceptor phenotypic cells in neurospheres have a potential to interact with rat retinal explants. Immunocytochemistry for rhodopsin and synaptophysin indicated photoreceptor cell-like differentiation in neurospheres that were stimulated by basic fibroblast growth factor and epidermal growth factor. Differentiation into neural phenotypes including photoreceptor cells was effectively blocked by an addition of leukemia inhibitory factor. Grafting of neurospheres onto retinal explants demonstrated a consistent penetration of glial cell processes into the explanted tissue. On the other hand, the incorporation of donor cells into explants was very low. A general finding was that neurospheres grafting was associated with local decrease in Müller cell activation in the explants. Further characterization of these effect(s) could provide further insight into progenitor cell-based therapies of retinal degenerative disorders.

  3. A slowly evolving host moves first in symbiotic interactions

    NASA Astrophysics Data System (ADS)

    Damore, James; Gore, Jeff

    2011-03-01

    Symbiotic relationships, both parasitic and mutualistic, are ubiquitous in nature. Understanding how these symbioses evolve, from bacteria and their phages to humans and our gut microflora, is crucial in understanding how life operates. Often, symbioses consist of a slowly evolving host species with each host only interacting with its own sub-population of symbionts. The Red Queen hypothesis describes coevolutionary relationships as constant arms races with each species rushing to evolve an advantage over the other, suggesting that faster evolution is favored. Here, we use a simple game theoretic model of host- symbiont coevolution that includes population structure to show that if the symbionts evolve much faster than the host, the equilibrium distribution is the same as it would be if it were a sequential game where the host moves first against its symbionts. For the slowly evolving host, this will prove to be advantageous in mutualisms and a handicap in antagonisms. The model allows for symbiont adaptation to its host, a result that is robust to changes in the parameters and generalizes to continuous and multiplayer games. Our findings provide insight into a wide range of symbiotic phenomena and help to unify the field of coevolutionary theory.

  4. Interactome of E. piscicida and grouper liver proteins reveals strategies of bacterial infection and host immune response

    PubMed Central

    Li, Hui; Zhu, Qing-feng; Peng, Xuan-xian; Peng, Bo

    2017-01-01

    The occurrence of infectious diseases is related to heterogeneous protein interactions between a host and a microbe. Therefore, elucidating the host-pathogen interplay is essential. We previously revealed the protein interactome between Edwardsiella piscicida and fish gill cells, and the present study identified the protein interactome between E. piscicida and E. drummondhayi liver cells. E. drummondhayi liver cells and bacterial pull-down approaches were used to identify E. piscicida outer membrane proteins that bind to liver cells and fish liver cell proteins that interact with bacterial cells, respectively. Eight bacterial proteins and 11 fish proteins were characterized. Heterogeneous protein-protein interactions between these bacterial cells and fish liver cells were investigated through far-Western blotting and co-immunoprecipitation. A network was constructed based on 42 heterogeneous protein-protein interactions between seven bacterial proteins and 10 fish proteins. A comparison of the new interactome with the previously reported interactome showed that four bacterial proteins overlapped, whereas all of the identified fish proteins were new, suggesting a difference between bacterial tricks for evading host immunity and the host strategy for combating bacterial infection. Furthermore, these bacterial proteins were found to regulate the expression of host innate immune-related proteins. These findings indicate that the interactome contributes to bacterial infection and host immunity. PMID:28045121

  5. Screening for Host Factors Directly Interacting with RSV Protein: Microfluidics.

    PubMed

    Kipper, Sarit; Avrahami, Dorit; Bajorek, Monika; Gerber, Doron

    2016-01-01

    We present a high-throughput microfluidics platform to identify novel host cell binding partners of respiratory syncytial virus (RSV) matrix (M) protein. The device consists of thousands of reaction chambers controlled by micro-mechanical valves. The microfluidic device is mated to a microarray-printed custom-made gene library. These genes are then transcribed and translated on-chip, resulting in a protein array ready for binding to RSV M protein.Even small viral proteome, such as that of RSV, presents a challenge due to the fact that viral proteins are usually multifunctional and thus their interaction with the host is complex. Protein microarrays technology allows the interrogation of protein-protein interactions, which could possibly overcome obstacles by using conventional high throughput methods. Using microfluidics platform we have identified new host interactors of M involved in various cellular pathways. A number of microfluidics based assays have already provided novel insights into the virus-host interactome, and the results have important implications for future antiviral strategies aimed at targets of viral protein interactions with the host.

  6. Dissection of Francisella-Host Cell Interactions in Dictyostelium discoideum.

    PubMed

    Lampe, Elisabeth O; Brenz, Yannick; Herrmann, Lydia; Repnik, Urska; Griffiths, Gareth; Zingmark, Carl; Sjöstedt, Anders; Winther-Larsen, Hanne C; Hagedorn, Monica

    2015-12-28

    Francisella bacteria cause severe disease in both vertebrates and invertebrates and include one of the most infectious human pathogens. Mammalian cell lines have mainly been used to study the mechanisms by which Francisella manipulates its host to replicate within a large variety of hosts and cell types, including macrophages. Here, we describe the establishment of a genetically and biochemically tractable infection model: the amoeba Dictyostelium discoideum combined with the fish pathogen Francisella noatunensis subsp. noatunensis. Phagocytosed F. noatunensis subsp. noatunensis interacts with the endosomal pathway and escapes further phagosomal maturation by translocating into the host cell cytosol. F. noatunensis subsp. noatunensis lacking IglC, a known virulence determinant required for Francisella intracellular replication, follows the normal phagosomal maturation and does not grow in Dictyostelium. The attenuation of the F. noatunensis subsp. noatunensis ΔiglC mutant was confirmed in a zebrafish embryo model, where growth of F. noatunensis subsp. noatunensis ΔiglC was restricted. In Dictyostelium, F. noatunensis subsp. noatunensis interacts with the autophagic machinery. The intracellular bacteria colocalize with autophagic markers, and when autophagy is impaired (Dictyostelium Δatg1), F. noatunensis subsp. noatunensis accumulates within Dictyostelium cells. Altogether, the Dictyostelium-F. noatunensis subsp. noatunensis infection model recapitulates the course of infection described in other host systems. The genetic and biochemical tractability of the system allows new approaches to elucidate the dynamic interactions between pathogenic Francisella and its host organism.

  7. Dissection of Francisella-Host Cell Interactions in Dictyostelium discoideum

    PubMed Central

    Lampe, Elisabeth O.; Brenz, Yannick; Herrmann, Lydia; Repnik, Urska; Griffiths, Gareth; Zingmark, Carl; Sjöstedt, Anders; Winther-Larsen, Hanne C.

    2015-01-01

    Francisella bacteria cause severe disease in both vertebrates and invertebrates and include one of the most infectious human pathogens. Mammalian cell lines have mainly been used to study the mechanisms by which Francisella manipulates its host to replicate within a large variety of hosts and cell types, including macrophages. Here, we describe the establishment of a genetically and biochemically tractable infection model: the amoeba Dictyostelium discoideum combined with the fish pathogen Francisella noatunensis subsp. noatunensis. Phagocytosed F. noatunensis subsp. noatunensis interacts with the endosomal pathway and escapes further phagosomal maturation by translocating into the host cell cytosol. F. noatunensis subsp. noatunensis lacking IglC, a known virulence determinant required for Francisella intracellular replication, follows the normal phagosomal maturation and does not grow in Dictyostelium. The attenuation of the F. noatunensis subsp. noatunensis ΔiglC mutant was confirmed in a zebrafish embryo model, where growth of F. noatunensis subsp. noatunensis ΔiglC was restricted. In Dictyostelium, F. noatunensis subsp. noatunensis interacts with the autophagic machinery. The intracellular bacteria colocalize with autophagic markers, and when autophagy is impaired (Dictyostelium Δatg1), F. noatunensis subsp. noatunensis accumulates within Dictyostelium cells. Altogether, the Dictyostelium-F. noatunensis subsp. noatunensis infection model recapitulates the course of infection described in other host systems. The genetic and biochemical tractability of the system allows new approaches to elucidate the dynamic interactions between pathogenic Francisella and its host organism. PMID:26712555

  8. Biomimetic Materials to Characterize Bacteria-host Interactions

    PubMed Central

    Vaz, Diana; Perez-Soto, Nicolas; Krachler, Anne M.

    2015-01-01

    Bacterial attachment to host cells is one of the earliest events during bacterial colonization of host tissues and thus a key step during infection. The biochemical and functional characterization of adhesins mediating these initial bacteria-host interactions is often compromised by the presence of other bacterial factors, such as cell wall components or secreted molecules, which interfere with the analysis. This protocol describes the production and use of biomimetic materials, consisting of pure recombinant adhesins chemically coupled to commercially available, functionalized polystyrene beads, which have been used successfully to dissect the biochemical and functional interactions between individual bacterial adhesins and host cell receptors. Protocols for different coupling chemistries, allowing directional immobilization of recombinant adhesins on polymer scaffolds, and for assessment of the coupling efficiency of the resulting “bacteriomimetic” materials are also discussed. We further describe how these materials can be used as a tool to inhibit pathogen mediated cytotoxicity and discuss scope, limitations and further applications of this approach in studying bacterial - host interactions. PMID:26650964

  9. Rotavirus in organ transplantation: drug-virus-host interactions.

    PubMed

    Yin, Y; Metselaar, H J; Sprengers, D; Peppelenbosch, M P; Pan, Q

    2015-03-01

    Although rotavirus is usually recognized as the most common etiology of diarrhea in young children, it can in fact cause severe diseases in organ transplantation recipients irrespective of pediatric or adult patients. This comprehensive literature analysis revealed 200 cases of rotavirus infection with 8 related deaths in the setting of organ transplantation been recorded. Based on published cohort studies, an average incidence of 3% (187 infections out of 6176 organ recipients) was estimated. Rotavirus infection often causes severe gastroenteritis complications and occasionally contributes to acute cellular rejection in these patients. Immunosuppressive agents, universally used after organ transplantation to prevent organ rejection, conceivably play an important role in such a severe pathogenesis. Interestingly, rotavirus can in turn affect the absorption and metabolism of particular immunosuppressive medications via several distinct mechanisms. Even though rotaviral enteritis is self-limiting in general, infected transplantation patients are usually treated with intensive care, rehydration and replacement of nutrition, as well as applying preventive strategies. This article aims to properly assess the clinical impact of rotavirus infection in the setting of organ transplantation and to disseminate the interactions among the virus, host and immunosuppressive medications.

  10. Precise Photoremovable Perturbation of a Virus-Host Interaction.

    PubMed

    Erickson, Sarah B; Mukherjee, Raja; Kelemen, Rachel E; Wrobel, Chester J J; Cao, Xiaofu; Chatterjee, Abhishek

    2017-04-03

    Viruses utilize distinct binding interactions with a variety of host factors to gain entry into host cells. A chemical strategy is described to precisely perturb a specific molecular interaction between adeno-associated virus and its host cell, which can be rapidly reversed by light. This strategy enables pausing the virus entry process at a specific stage and then restart it rapidly with a non-invasive stimulus. The ability to synchronize the invading virus population at a discrete step in its entry pathway will be highly valuable for enabling facile experimental characterization of the molecular processes underlying this process. Additionally, adeno-associated virus has demonstrated outstanding potential for human gene therapy. This work further provides a potential approach to create therapeutic vectors that can be photoactivated in vivo with high spatial and temporal control.

  11. Structure-based prediction of host-pathogen protein interactions.

    PubMed

    Mariano, Rachelle; Wuchty, Stefan

    2017-03-16

    The discovery, validation, and characterization of protein-based interactions from different species are crucial for translational research regarding a variety of pathogens, ranging from the malaria parasite Plasmodium falciparum to HIV-1. Here, we review recent advances in the prediction of host-pathogen protein interfaces using structural information. In particular, we observe that current methods chiefly perform machine learning on sequence and domain information to produce large sets of candidate interactions that are further assessed and pruned to generate final, highly probable sets. Structure-based studies have also emphasized the electrostatic properties and evolutionary transformations of pathogenic interfaces, supplying crucial insight into antigenic determinants and the ways pathogens compete for host protein binding. Advancements in spectroscopic and crystallographic methods complement the aforementioned techniques, permitting the rigorous study of true positives at a molecular level. Together, these approaches illustrate how protein structure on a variety of levels functions coordinately and dynamically to achieve host takeover.

  12. Host/pathogen interactions and immune effector mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An understanding of the host/pathogen interactions for mycobacterial infections underpins many of the outcomes required for improving disease control, including better diagnostic tests, vaccines and breeding for disease resistance. Upon infection these mycobacteria come in contact with cells of the ...

  13. Inactivation of Wolbachia Reveals Its Biological Roles in Whitefly Host

    PubMed Central

    Xue, Xia; Li, Shao-Jian; Ahmed, Muhammad Z.; De Barro, Paul J.; Ren, Shun-Xiang; Qiu, Bao-Li

    2012-01-01

    Background The whitefly Bemisia tabaci is cryptic species complex composed of numerous species. Individual species from the complex harbor a diversity of bacterial endosymbionts including Wolbachia. However, while Wolbachia is known to have a number of different roles, its role in B. tabaci is unclear. Here, the antibiotic rifampicin is used to selectively eliminate Wolbachia from B. tabaci so as to enable its roles in whitefly development and reproduction to be explored. The indirect effects of Wolbachia elimination on the biology of Encarsia bimaculata, a dominant parasitoid of B. tabaci in South China, were also investigated. Methodology/Principal Finding qRT-PCR and FISH were used to show that after 48 h exposure to 1.0 mg/ml rifampicin, Wolbachia was completely inactivated from B. tabaci Mediterranean (MED) without any significant impact on either the primary symbiont, Portiera aleyrodidarum or any of the other secondary endosymbionts present. For B. tabaci MED, Wolbachia was shown to be associated with decreased juvenile development time, increased likelihood that nymphs completed development, increased adult life span and increased percentage of female progeny. Inactivation was associated with a significant decrease in the body size of the 4th instar which leads us to speculate as to whether Wolbachia may have a nutrient supplementation role. The reduction in nymph body size has consequences for its parasitoid, E. bimaculata. The elimination of Wolbachia lead to a marked increase in the proportion of parasitoid eggs that completed their development, but the reduced size of the whitefly host was also associated with a significant reduction in the size of the emerging parasitoid adult and this was in turn associated with a marked reduction in adult parasitoid longevity. Conclusions/Significance Wolbachia increases the fitness of the whitefly host and provides some protection against parasitization. These observations add to our understanding of the roles

  14. Vertebrate host specificity of wild-caught blackflies revealed by mitochondrial DNA in blood.

    PubMed

    Malmqvist, Björn; Strasevicius, Darius; Hellgren, Olof; Adler, Peter H; Bensch, Staffan

    2004-05-07

    Blood-feeding blackflies (Diptera: Simuliidae) transmit pathogens, harass vertebrate hosts and may cause lethal injuries in attacked victims, but with traditional methods it has proved difficult to identify their hosts. By matching mitochondrial DNA (mtDNA) sequences in blood collected from engorged blackflies with stored sequences in the GenBank database, relationships between 17 blackfly species and 25 species of vertebrate hosts were revealed. Our results demonstrate a predominance of large hosts and marked discrimination between blackflies using either avian or mammalian hosts. Such information is of vital interest in studies of disease transmission, coevolutionary relationships, population ecology and wildlife management.

  15. Specialization for resistance in wild host-pathogen interaction networks.

    PubMed

    Barrett, Luke G; Encinas-Viso, Francisco; Burdon, Jeremy J; Thrall, Peter H

    2015-01-01

    Properties encompassed by host-pathogen interaction networks have potential to give valuable insight into the evolution of specialization and coevolutionary dynamics in host-pathogen interactions. However, network approaches have been rarely utilized in previous studies of host and pathogen phenotypic variation. Here we applied quantitative analyses to eight networks derived from spatially and temporally segregated host (Linum marginale) and pathogen (Melampsora lini) populations. First, we found that resistance strategies are highly variable within and among networks, corresponding to a spectrum of specialist and generalist resistance types being maintained within all networks. At the individual level, specialization was strongly linked to partial resistance, such that partial resistance was effective against a greater number of pathogens compared to full resistance. Second, we found that all networks were significantly nested. There was little support for the hypothesis that temporal evolutionary dynamics may lead to the development of nestedness in host-pathogen infection networks. Rather, the common patterns observed in terms of nestedness suggests a universal driver (or multiple drivers) that may be independent of spatial and temporal structure. Third, we found that resistance networks were significantly modular in two spatial networks, clearly reflecting spatial and ecological structure within one of the networks. We conclude that (1) overall patterns of specialization in the networks we studied mirror evolutionary trade-offs with the strength of resistance; (2) that specific network architecture can emerge under different evolutionary scenarios; and (3) network approaches offer great utility as a tool for probing the evolutionary and ecological genetics of host-pathogen interactions.

  16. Microsatellite analysis reveals strong but differential impact of a social parasite on its two host species.

    PubMed

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

    2006-03-01

    The speed and the dynamics of the co-evolutionary process strongly depend on the relative strengths of reciprocal selection pressures exerted by the interacting species. Here, we investigate the influence of an obligate social parasite, the slave-making ant Harpagoxenus sublaevis, on populations of the two main host species Leptothorax acervorum and Leptothorax muscorum from a German ant community. A combination of genetic and demographic data allowed us to analyse the consequences of raiding pressure on the hosts' life history and possible host preferences of the parasite. We can demonstrate that slave raids during which the social parasite pillages brood from neighbouring host colonies are both frequent and extremely destructive for both host species. Microsatellite analysis showed that, on average, a single slave-maker colony conducts more than three raids per year and that host colonies mostly perish in the aftermath of these parasite attacks. Only in few cases, surviving nests of previously raided host colonies were found in the surroundings of slave-maker colonies. As a consequence of the high prevalence of parasites and their recurrent and devastating slave raids on host colonies, the life expectancy of host colonies was severely reduced. Combining our results on host-specific parasitic colony founding and raiding frequencies with the post-raid survival rate, we can demonstrate an overall higher mortality rate for the smaller host species L. muscorum. This might be caused by a preference of H. sublaevis for this secondary host species as demographic data on host species usage indicate.

  17. Interactions of Host Proteins with the Murine Leukemia Virus Integrase

    PubMed Central

    Studamire, Barbara; Goff, Stephen P.

    2010-01-01

    Retroviral infections cause a variety of cancers in animals and a number of diverse diseases in humans such as leukemia and acquired immune deficiency syndrome. Productive and efficient proviral integration is critical for retroviral function and is the key step in establishing a stable and productive infection, as well as the mechanism by which host genes are activated in leukemogenesis. Host factors are widely anticipated to be involved in all stages of the retroviral life cycle, and the identification of integrase interacting factors has the potential to increase our understanding of mechanisms by which the incoming virus might appropriate cellular proteins to target and capture host DNA sequences. Identification of MoMLV integrase interacting host factors may be key to designing efficient and benign retroviral-based gene therapy vectors; key to understanding the basic mechanism of integration; and key in designing efficient integrase inhibitors. In this review, we discuss current progress in the field of MoMLV integrase interacting proteins and possible roles for these proteins in integration. PMID:21637732

  18. Pathogens and polymers: Microbe–host interactions illuminate the cytoskeleton

    PubMed Central

    Haglund, Cat M.

    2011-01-01

    Intracellular pathogens subvert the host cell cytoskeleton to promote their own survival, replication, and dissemination. Study of these microbes has led to many discoveries about host cell biology, including the identification of cytoskeletal proteins, regulatory pathways, and mechanisms of cytoskeletal function. Actin is a common target of bacterial pathogens, but recent work also highlights the use of microtubules, cytoskeletal motors, intermediate filaments, and septins. The study of pathogen interactions with the cytoskeleton has illuminated key cellular processes such as phagocytosis, macropinocytosis, membrane trafficking, motility, autophagy, and signal transduction. PMID:21969466

  19. Host restriction factors in retroviral infection: promises in virus-host interaction

    PubMed Central

    2012-01-01

    Retroviruses have an intricate life cycle. There is much to be learned from studying retrovirus-host interactions. Among retroviruses, the primate lentiviruses have one of the more complex genome structures with three categories of viral genes: structural, regulatory, and accessory genes. Over time, we have gained increasing understanding of the lentivirus life cycle from studying host factors that support virus replication. Similarly, studies on host restriction factors that inhibit viral replication have also made significant contributions to our knowledge. Here, we review recent progress on the rapidly growing field of restriction factors, focusing on the antiretroviral activities of APOBEC3G, TRIM5, tetherin, SAMHD1, MOV10, and cellular microRNAs (miRNAs), and the counter-activities of Vif, Vpu, Vpr, Vpx, and Nef. PMID:23254112

  20. Interactions between host factors and the skin microbiome

    PubMed Central

    SanMiguel, Adam; Grice, Elizabeth A.

    2015-01-01

    The skin is colonized by an assemblage of microorganisms which, for the most part, peacefully coexist with their hosts. In some cases, these communities also provide vital functions to cutaneous health through the modulation of host factors. Recent studies have illuminated the role of anatomical skin site, gender, age, and the immune system in shaping the cutaneous ecosystem. Alterations to microbial communities have also been associated with, and likely contribute to, a number of cutaneous disorders. This review focuses on the host factors that shape and maintain skin microbial communities, and the reciprocal role of microbes in modulating skin immunity. A greater understanding of these interactions is critical to elucidating the forces that shape cutaneous populations and their contributions to skin homeostasis. This knowledge can also inform the tendency of perturbations to predispose and/or bring about certain skin disorders. PMID:25548803

  1. Host-pathogen interactions between the skin and Staphylococcus aureus.

    PubMed

    Krishna, Sheila; Miller, Lloyd S

    2012-02-01

    Staphylococcus aureus is responsible for the vast majority of bacterial skin infections in humans. The propensity for S. aureus to infect skin involves a balance between cutaneous immune defense mechanisms and virulence factors of the pathogen. The tissue architecture of the skin is different from other epithelia especially since it possesses a corneal layer, which is an important barrier that protects against the pathogenic microorganisms in the environment. The skin surface, epidermis, and dermis all contribute to host defense against S. aureus. Conversely, S. aureus utilizes various mechanisms to evade these host defenses to promote colonization and infection of the skin. This review will focus on host-pathogen interactions at the skin interface during the pathogenesis of S. aureus colonization and infection.

  2. Emerging Supramolecular Therapeutic Carriers Based on Host-Guest Interactions.

    PubMed

    Karim, Anis Abdul; Dou, Qingqing; Li, Zibiao; Loh, Xian Jun

    2016-05-06

    Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non-covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self-assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site-specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed.

  3. Norovirus-host interaction: multi-selections by human HBGAs

    PubMed Central

    Tan, Ming; Jiang, Xi

    2011-01-01

    The discovery of human histo-blood group antigens (HBGAs) as receptors or ligands of noroviruses (NoVs) raises a question about the potential role of host factors in the evolution and diversity of NoVs. Recent structural analysis of selected strains in the two major genogroups of human NoVs (GI and GII) demonstrated highly conserved HBGA binding interfaces within the two groups but not between them, indicating convergent evolution of GI and GII NoVs. GI and GII NoVs are likely introduced to humans from different non-human hosts with the HBGAs as a common niche. Each genogroup has further diverged into multiple sub-lineages (genotypes) through selections by the polymorphic HBGAs of the hosts. An elucidation of such pathogen-host interaction, including determination of the phenotypes of NoV-HBGAs interaction for each genotype, is important in understanding the epidemiology, classification and disease control and prevention of NoVs. A model of this multi-selection of NoVs by HBGAs is proposed. PMID:21705222

  4. Virus genomes and virus-host interactions in aquaculture animals.

    PubMed

    Zhang, QiYa; Gui, Jian-Fang

    2015-02-01

    Over the last 30 years, aquaculture has become the fastest growing form of agriculture production in the world, but its development has been hampered by a diverse range of pathogenic viruses. During the last decade, a large number of viruses from aquatic animals have been identified, and more than 100 viral genomes have been sequenced and genetically characterized. These advances are leading to better understanding about antiviral mechanisms and the types of interaction occurring between aquatic viruses and their hosts. Here, based on our research experience of more than 20 years, we review the wealth of genetic and genomic information from studies on a diverse range of aquatic viruses, including iridoviruses, herpesviruses, reoviruses, and rhabdoviruses, and outline some major advances in our understanding of virus-host interactions in animals used in aquaculture.

  5. Identification of sequence motifs involved in Dengue virus-host interactions.

    PubMed

    Asnet Mary, J; Paramasivan, R; Shenbagarathai, R

    2016-01-01

    Dengue fever is a rapidly spreading mosquito-borne virus infection, which remains a serious global public health problem. As there is no specific treatment or commercial vaccine available for effective control of the disease, the attempts on developing novel control strategies are underway. Viruses utilize the surface receptor proteins of host to enter into the cells. Though various proteins were said to be receptors of Dengue virus (DENV) using Virus Overlay Protein Binding Assay, the precise interaction between DENV and host is not explored. Understanding the structural features of domain III envelope glycoprotein would help in developing efficient antiviral inhibitors. Therefore, an attempt was made to identify the sequence motifs present in domain III envelope glycoprotein of Dengue virus. Computational analysis revealed that the NGR motif is present in the domain III envelope glycoprotein of DENV-1 and DENV-3. Similarly, DENV-1, DENV-2 and DENV-4 were found to contain Yxxphi motif which is a tyrosine-based sorting signal responsible for the interaction with a mu subunit of adaptor protein complex. High-throughput virtual screening resulted in five compounds as lead molecules based on glide score, which ranges from -4.664 to -6.52 kcal/Mol. This computational prediction provides an additional tool for understanding the virus-host interactions and helps to identify potential targets in the host. Further, experimental evidence is warranted to confirm the virus-host interactions and also inhibitory activity of reported lead compounds.

  6. Salmonella pathogenicity islands in host specificity, host pathogen-interactions and antibiotics resistance of Salmonella enterica.

    PubMed

    Gerlach, Roman G; Hensel, Michael

    2007-01-01

    Salmonella enterica is a pathogen highly successful in causing a variety of gastrointestinal and systemic diseases in animals and humans. While some serovars of S. enterica are able to infect a broad range of host organisms, other serovars are highly restricted to specific host species. The colonization of hosts by S. enterica depends on the function of a large number of virulence determinants. The molecular analyses of virulence genes demonstrated that most of these loci are clustered within Salmonella Pathogenicity Islands (SPI). SPI1 and SPI2 each encode type III secretion systems (T355) that confer main virulence traits of S. enterica, i.e. invasion, enteropathogenesis and intracellular survival and proliferation. Further SPI encode factors that contribute to intracellular survival, different types of adhesins, or effector proteins of the SPI1-T3SS or SPI2-T3SS. The availability of genome sequences of several serovars of S. enterica also revealed serovar-specific SPI. In this review, the main characteristics of the currently known SPI are summarized with focus on their roles in various animal hosts and putative functions in human infections.

  7. Host and non-host roots in rice: cellular and molecular approaches reveal differential responses to arbuscular mycorrhizal fungi

    PubMed Central

    Fiorilli, Valentina; Vallino, Marta; Biselli, Chiara; Faccio, Antonella; Bagnaresi, Paolo; Bonfante, Paola

    2015-01-01

    Oryza sativa, a model plant for Arbuscular Mycorrhizal (AM) symbiosis, has both host and non-host roots. Large lateral (LLR) and fine lateral (FLR) roots display opposite responses: LLR support AM colonization, but FLR do not. Our research aimed to study the molecular, morphological and physiological aspects related to the non-host behavior of FLR. RNA-seq analysis revealed that LLR and FLR displayed divergent expression profiles, including changes in many metabolic pathways. Compared with LLR, FLR showed down-regulation of genes instrumental for AM establishment and gibberellin signaling, and a higher expression of nutrient transporters. Consistent with the transcriptomic data, FLR had higher phosphorus content. Light and electron microscopy demonstrated that, surprisingly, in the Selenio cultivar, FLR have a two-layered cortex, which is theoretically compatible with AM colonization. According to RNA-seq, a gibberellin inhibitor treatment increased anticlinal divisions leading to a higher number of cortex cells in FLR. We propose that some of the differentially regulated genes that lead to the anatomical and physiological properties of the two root types also function as genetic factors regulating fungal colonization. The rice root apparatus offers a unique tool to study AM symbiosis, allowing direct comparisons of host and non-host roots in the same individual plant. PMID:26322072

  8. Food availability affects the strength of mutualistic host-microbiota interactions in Daphnia magna.

    PubMed

    Callens, Martijn; Macke, Emilie; Muylaert, Koenraad; Bossier, Peter; Lievens, Bart; Waud, Michael; Decaestecker, Ellen

    2016-04-01

    The symbiotic gut microbial community is generally known to have a strong impact on the fitness of its host. Nevertheless, it is less clear how the impact of symbiotic interactions on the hosts' fitness varies according to environmental circumstances such as changes in the diet. This study aims to get a better understanding of host-microbiota interactions under different levels of food availability. We conducted experiments with the invertebrate, experimental model organism Daphnia magna and compared growth, survival and reproduction of conventionalized symbiotic Daphnia with germ-free individuals given varying quantities of food. Our experiments revealed that the relative importance of the microbiota for the hosts' fitness varied according to dietary conditions. The presence of the microbiota had strong positive effects on Daphnia when food was sufficient or abundant, but had weaker effects under food limitation. Our results indicate that the microbiota can be a potentially important factor in determining host responses to changes in dietary conditions. Characterization of the host-associated microbiota further showed that Aeromonas sp. was the most prevalent taxon in the digestive tract of Daphnia.

  9. Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes.

    PubMed

    Davis, Zoe H; Verschueren, Erik; Jang, Gwendolyn M; Kleffman, Kevin; Johnson, Jeffrey R; Park, Jimin; Von Dollen, John; Maher, M Cyrus; Johnson, Tasha; Newton, William; Jäger, Stefanie; Shales, Michael; Horner, Julie; Hernandez, Ryan D; Krogan, Nevan J; Glaunsinger, Britt A

    2015-01-22

    Mapping host-pathogen interactions has proven instrumental for understanding how viruses manipulate host machinery and how numerous cellular processes are regulated. DNA viruses such as herpesviruses have relatively large coding capacity and thus can target an extensive network of cellular proteins. To identify the host proteins hijacked by this pathogen, we systematically affinity tagged and purified all 89 proteins of Kaposi's sarcoma-associated herpesvirus (KSHV) from human cells. Mass spectrometry of this material identified over 500 virus-host interactions. KSHV causes AIDS-associated cancers, and its interaction network is enriched for proteins linked to cancer and overlaps with proteins that are also targeted by HIV-1. We found that the conserved KSHV protein ORF24 binds to RNA polymerase II and brings it to viral late promoters by mimicking and replacing cellular TATA-box-binding protein (TBP). This is required for herpesviral late gene expression, a complex and poorly understood phase of the viral lifecycle.

  10. Towards a better understanding of Lactobacillus rhamnosus GG - host interactions

    PubMed Central

    2014-01-01

    Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains. PMID:25186587

  11. Egg colour mimicry in the common cuckoo Cuculus canorus as revealed by modelling host retinal function

    PubMed Central

    Avilés, Jesús M

    2008-01-01

    Some parasite cuckoo species lay eggs that, to the human eye, appear to mimic the appearance of the eggs of their favourite hosts, which hinders discrimination and removal of their eggs by host species. Hitherto, perception of cuckoo–host egg mimicry has been estimated based on human vision or spectrophotometry, which does not account for what the receivers' eye (i.e. hosts) actually discriminates. Using a discrimination model approach that reproduces host retinal functioning, and museum egg collections collected in the south of Finland, where at least six different races of the European cuckoo (Cuculus canorus) coexist, I first assess whether the colour design of cuckoo eggs of different races maximizes matching for two favourite avian hosts, viz. the redstart (Phoenicurus phoenicurus) and the pied wagtail (Motacilla alba). Second, I assess the role of nest luminosity on host perception of mimicry by the same two hosts. Phoenicurus-cuckoo eggs showed a better chromatic matching with the redstart-host eggs than other cuckoo races, and in most cases can not be discriminated. Sylvia-cuckoo eggs, however, showed better achromatic matching with redstart-host eggs than Phoenicurus-cuckoo eggs. Also, Motacilla-cuckoo eggs showed poorer chromatic and achromatic matching with pied wagtail-host eggs than Sylvia-cuckoo eggs. Nest luminosity affected chromatic and achromatic differences between cuckoo and host eggs, although only minimally affected the proportion of cuckoo eggs discriminated by chromatic signals. These results reveal that cuckoo races as assessed by humans do not entirely match with host perception of matching and that achromatic mechanisms could play a main role in the discrimination of cuckoo eggs at low-light levels. PMID:18595836

  12. Egg colour mimicry in the common cuckoo Cuculus canorus as revealed by modelling host retinal function.

    PubMed

    Avilés, Jesús M

    2008-10-22

    Some parasite cuckoo species lay eggs that, to the human eye, appear to mimic the appearance of the eggs of their favourite hosts, which hinders discrimination and removal of their eggs by host species. Hitherto, perception of cuckoo-host egg mimicry has been estimated based on human vision or spectrophotometry, which does not account for what the receivers' eye (i.e. hosts) actually discriminates. Using a discrimination model approach that reproduces host retinal functioning, and museum egg collections collected in the south of Finland, where at least six different races of the European cuckoo (Cuculus canorus) coexist, I first assess whether the colour design of cuckoo eggs of different races maximizes matching for two favourite avian hosts, viz. the redstart (Phoenicurus phoenicurus) and the pied wagtail (Motacilla alba). Second, I assess the role of nest luminosity on host perception of mimicry by the same two hosts. Phoenicurus-cuckoo eggs showed a better chromatic matching with the redstart-host eggs than other cuckoo races, and in most cases can not be discriminated. Sylvia-cuckoo eggs, however, showed better achromatic matching with redstart-host eggs than Phoenicurus-cuckoo eggs. Also, Motacilla-cuckoo eggs showed poorer chromatic and achromatic matching with pied wagtail-host eggs than Sylvia-cuckoo eggs. Nest luminosity affected chromatic and achromatic differences between cuckoo and host eggs, although only minimally affected the proportion of cuckoo eggs discriminated by chromatic signals. These results reveal that cuckoo races as assessed by humans do not entirely match with host perception of matching and that achromatic mechanisms could play a main role in the discrimination of cuckoo eggs at low-light levels.

  13. Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity

    PubMed Central

    Nielsen, Judith N.; Charlier, Caroline; Baltes, Nicholas J.; Chrétien, Fabrice; Heitman, Joseph; Dromer, Françoise; Nielsen, Kirsten

    2010-01-01

    Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection. PMID:20585559

  14. The remarkable capacity for gut microbial and host interactions

    PubMed Central

    Nagy-Szakal, Dorottya

    2011-01-01

    The stunning complexity of the resident microbiota and the intricate pathways of microbial and host interactions provide a massive adaptive capacity for mammals. In this addendum we reflect on our recent publication on Toll-like receptor 2 deficiency related colonic mucosal epigenetic, immunologic and microbiomic changes. Our findings underscored the tremendous flexibility of the gut and its microbiota. This flexibility can provide means to overcome significant environmental or genetic challenges. In the meantime, the challenged intestinal system may become vulnerable to otherwise tolerable insults. In such instances, the fine-tuned mutualistic balance between the gut and its microflora may collapse leading to dysbiosis and disease. The ultimate challenge for biomedical research in these cases is to find optimal means for the restoration and maintenance of healthy host physiology. PMID:21646867

  15. Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity

    PubMed Central

    Everard, Amandine; Lazarevic, Vladimir; Gaïa, Nadia; Johansson, Maria; Ståhlman, Marcus; Backhed, Fredrik; Delzenne, Nathalie M; Schrenzel, Jacques; François, Patrice; Cani, Patrice D

    2014-01-01

    The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of the gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota–host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by ∼50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups (COGs) of proteins also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding. PMID:24694712

  16. Visualization of host-polerovirus interaction topologies using Protein Interaction Reporter technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. The majority of interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll viru...

  17. Students' Peer Interactions within a Cohort and in Host Countries during a Short-Term Study Abroad

    ERIC Educational Resources Information Center

    Jessup-Anger, Jody E.; Aragones, Aileen

    2013-01-01

    In this qualitative case study, we explored students' peer interactions within their cohort and in the host countries during a short-term study abroad. Framed by Bronfenbrenner's (1993) ecological systems theory, findings revealed that students spent considerable energy reflecting on interactions with peers. The students considered themselves…

  18. Multihost experimental evolution of a plant RNA virus reveals local adaptation and host-specific mutations.

    PubMed

    Bedhomme, Stéphanie; Lafforgue, Guillaume; Elena, Santiago F

    2012-05-01

    For multihost pathogens, adaptation to multiple hosts has important implications for both applied and basic research. At the applied level, it is one of the main factors determining the probability and the severity of emerging disease outbreaks. At the basic level, it is thought to be a key mechanism for the maintenance of genetic diversity both in host and pathogen species. Using Tobacco etch potyvirus (TEV) and four natural hosts, we have designed an evolution experiment whose strength and novelty are the use of complex multicellular host organism as hosts and a high level of replication of different evolutionary histories and lineages. A pattern of local adaptation, characterized by a higher infectivity and virulence on host(s) encountered during the experimental evolution was found. Local adaptation only had a cost in terms of performance on other hosts in some cases. We could not verify the existence of a cost for generalists, as expected to arise from antagonistic pleiotropy and other genetic mechanisms generating a fitness trade-off between hosts. This observation confirms that this classical theoretical prediction lacks empirical support. We discuss the reasons for this discrepancy between theory and experiment in the light of our results. The analysis of full genome consensus sequences of the evolved lineages established that all mutations shared between lineages were host specific. A low degree of parallel evolution was observed, possibly reflecting the various adaptive pathways available for TEV in each host. Altogether, these results reveal a strong adaptive potential of TEV to new hosts without severe evolutionary constraints.

  19. Network analysis reveals common host protein/s modulating pathogenesis of neurotropic viruses

    PubMed Central

    Ghosh, Sourish; Mukherjee, Sriparna; Sengupta, Nabonita; Roy, Arunava; Dey, Dhritiman; Chakraborty, Surajit; Chattopadhyay, Dhrubajyoti; Banerjee, Arpan; Basu, Anirban

    2016-01-01

    Network analysis through graph theory provides a quantitative approach to characterize specific proteins and their constituent assemblies that underlie host-pathogen interactions. In the present study, graph theory was used to analyze the interactome designed out of 50 differentially expressing proteins from proteomic analysis of Chandipura Virus (CHPV, Family: Rhabdoviridae) infected mouse brain tissue to identify the primary candidates for intervention. Using the measure of degree centrality, that quantifies the connectedness of a single protein within a milieu of several other interacting proteins, DJ-1 was selected for further molecular validation. To elucidate the generality of DJ-1’s role in propagating infection its role was also monitored in another RNA virus, Japanese Encephalitis Virus (JEV, Family: Flaviviridae) infection. Concurrently, DJ-1 got over-expressed in response to reactive oxygen species (ROS) generation following viral infection which in the early phase of infection migrated to mitochondria to remove dysfunctional mitochondria through the process of mitophagy. DJ-1 was also observed to modulate the viral replication and interferon responses along with low-density lipoprotein (LDL) receptor expression in neurons. Collectively these evidences reveal a comprehensive role for DJ-1 in neurotropic virus infection in the brain. PMID:27581498

  20. Elucidating Novel Hepatitis C Virus–Host Interactions Using Combined Mass Spectrometry and Functional Genomics Approaches*

    PubMed Central

    Germain, Marie-Anne; Chatel-Chaix, Laurent; Gagné, Bridget; Bonneil, Éric; Thibault, Pierre; Pradezynski, Fabrine; de Chassey, Benoît; Meyniel-Schicklin, Laurène; Lotteau, Vincent; Baril, Martin; Lamarre, Daniel

    2014-01-01

    More than 170 million people worldwide are infected with the hepatitis C virus (HCV), for which future therapies are expected to rely upon a combination of oral antivirals. For a rapidly evolving virus like HCV, host-targeting antivirals are an attractive option. To decipher the role of novel HCV–host interactions, we used a proteomics approach combining immunoprecipitation of viral–host protein complexes coupled to mass spectrometry identification and functional genomics RNA interference screening of HCV partners. Here, we report the proteomics analyses of protein complexes associated with Core, NS2, NS3/4A, NS4B, NS5A, and NS5B proteins. We identified a stringent set of 98 human proteins interacting specifically with one of the viral proteins. The overlap with previous virus–host interaction studies demonstrates 24.5% shared HCV interactors overall (24/98), illustrating the reliability of the approach. The identified human proteins show enriched Gene Ontology terms associated with the endoplasmic reticulum, transport proteins with a major contribution of NS3/4A interactors, and transmembrane proteins for Core interactors. The interaction network emphasizes a high degree distribution, a high betweenness distribution, and high interconnectivity of targeted human proteins, in agreement with previous virus–host interactome studies. The set of HCV interactors also shows extensive enrichment for known targets of other viruses. The combined proteomic and gene silencing study revealed strong enrichment in modulators of HCV RNA replication, with the identification of 11 novel cofactors among our set of specific HCV partners. Finally, we report a novel immune evasion mechanism of NS3/4A protein based on its ability to affect nucleocytoplasmic transport of type I interferon-mediated signal transducer and activator of transcription 1 nuclear translocation. The study revealed highly stringent association between HCV interactors and their functional contribution to the

  1. Salmonella–Host Interactions – Modulation of the Host Innate Immune System

    PubMed Central

    Hurley, Daniel; McCusker, Matthew P.; Fanning, Séamus; Martins, Marta

    2014-01-01

    Salmonella enterica (S. enterica) are Gram-negative bacteria that can invade a broad range of hosts causing both acute and chronic infections. This phenotype is related to its ability to replicate and persist within non-phagocytic host epithelial cells as well as phagocytic dendritic cells and macrophages of the innate immune system. Infection with S. enterica manifests itself through a broad range of clinical symptoms and can result in asymptomatic carriage, gastroenteritis, systemic disease such as typhoid fever and in severe cases, death (1). Exposure to S. enterica serovars Typhi and Paratyphi exhibits clinical symptoms including diarrhea, fatigue, fever, and temperature fluctuations. Other serovars such as the non-typhoidal Salmonella (NTS), of which there are over 2,500, are commonly contracted as, but not limited to, food-borne sources causing gastrointestinal symptoms, which include diarrhea and vomiting. The availability of complete genome sequences for many S. enterica serovars has facilitated research into the genetic determinants of virulence for this pathogen. This work has led to the identification of important bacterial components, including flagella, type III secretion systems, lipopolysaccharides, and Salmonella pathogenicity islands, all of which support the intracellular life cycle of S. enterica. Studies focusing on the host–pathogen interaction have provided insights into receptor activation of the innate immune system. Therefore, characterizing the host–S. enterica interaction is critical to understand the pathogenicity of the bacteria in a clinically relevant context. This review outlines salmonellosis and the clinical manifestations between typhoidal and NTS infections as well as discussing the host immune response to infection and the models that are being used to elucidate the mechanisms involved in Salmonella pathogenicity. PMID:25339955

  2. Study Bacteria-Host Interactions Using Intestinal Organoids.

    PubMed

    Zhang, Yong-Guo; Sun, Jun

    2016-08-19

    The intestinal epithelial cells function to gain nutrients, retain water and electrolytes, and form an efficient barrier against foreign microbes and antigens. Researchers employed cell culture lines derived from human or animal cancer cells as experimental models in vitro for understanding of intestinal infections. However, most in vitro models used to investigate interactions between bacteria and intestinal epithelial cells fail to recreate the differentiated tissue components and structure observed in the normal intestine. The in vitro analysis of host-bacteria interactions in the intestine has been hampered by a lack of suitable intestinal epithelium culture systems. Here, we present a new experimental model using an organoid culture system to study bacterial infection.

  3. Mammalian microRNA: an important modulator of host-pathogen interactions in human viral infections.

    PubMed

    Ojha, Chet Raj; Rodriguez, Myosotys; Dever, Seth M; Mukhopadhyay, Rita; El-Hage, Nazira

    2016-10-26

    MicroRNAs (miRNAs), which are small non-coding RNAs expressed by almost all metazoans, have key roles in the regulation of cell differentiation, organism development and gene expression. Thousands of miRNAs regulating approximately 60 % of the total human genome have been identified. They regulate genetic expression either by direct cleavage or by translational repression of the target mRNAs recognized through partial complementary base pairing. The active and functional unit of miRNA is its complex with Argonaute proteins known as the microRNA-induced silencing complex (miRISC). De-regulated miRNA expression in the human cell may contribute to a diverse group of disorders including cancer, cardiovascular dysfunctions, liver damage, immunological dysfunction, metabolic syndromes and pathogenic infections. Current day studies have revealed that miRNAs are indeed a pivotal component of host-pathogen interactions and host immune responses toward microorganisms. miRNA is emerging as a tool for genetic study, therapeutic development and diagnosis for human pathogenic infections caused by viruses, bacteria, parasites and fungi. Many pathogens can exploit the host miRNA system for their own benefit such as surviving inside the host cell, replication, pathogenesis and bypassing some host immune barriers, while some express pathogen-encoded miRNA inside the host contributing to their replication, survival and/or latency. In this review, we discuss the role and significance of miRNA in relation to some pathogenic viruses.

  4. Hepatitis A virus: host interactions, molecular epidemiology and evolution.

    PubMed

    Vaughan, Gilberto; Goncalves Rossi, Livia Maria; Forbi, Joseph C; de Paula, Vanessa S; Purdy, Michael A; Xia, Guoliang; Khudyakov, Yury E

    2014-01-01

    Infection with hepatitis A virus (HAV) is the commonest viral cause of liver disease and presents an important public health problem worldwide. Several unique HAV properties and molecular mechanisms of its interaction with host were recently discovered and should aid in clarifying the pathogenesis of hepatitis A. Genetic characterization of HAV strains have resulted in the identification of different genotypes and subtypes, which exhibit a characteristic worldwide distribution. Shifts in HAV endemicity occurring in different parts of the world, introduction of genetically diverse strains from geographically distant regions, genotype displacement observed in some countries and population expansion detected in the last decades of the 20th century using phylogenetic analysis are important factors contributing to the complex dynamics of HAV infections worldwide. Strong selection pressures, some of which, like usage of deoptimized codons, are unique to HAV, limit genetic variability of the virus. Analysis of subgenomic regions has been proven useful for outbreak investigations. However, sharing short sequences among epidemiologically unrelated strains indicates that specific identification of HAV strains for molecular surveillance can be achieved only using whole-genome sequences. Here, we present up-to-date information on the HAV molecular epidemiology and evolution, and highlight the most relevant features of the HAV-host interactions.

  5. Patterns of plant subcellular responses to successful oomycete infections reveal differences in host cell reprogramming and endocytic trafficking

    PubMed Central

    Lu, Yi-Ju; Schornack, Sebastian; Spallek, Thomas; Geldner, Niko; Chory, Joanne; Schellmann, Swen; Schumacher, Karin; Kamoun, Sophien; Robatzek, Silke

    2016-01-01

    Summary Adapted filamentous pathogens such as the oomycetes Hyaloperonospora arabidopsidis (Hpa) and Phytophthora infestans (Pi) project specialized hyphae, the haustoria, inside living host cells for the suppression of host defence and acquisition of nutrients. Accommodation of haustoria requires reorganization of the host cell and the biogenesis of a novel host cell membrane, the extrahaustorial membrane (EHM), which envelops the haustorium separating the host cell from the pathogen. Here, we applied live-cell imaging of fluorescent-tagged proteins labelling a variety of membrane compartments and investigated the subcellular changes associated with accommodating oomycete haustoria in Arabidopsis and N. benthamiana. Plasma membrane-resident proteins differentially localized to the EHM. Likewise, secretory vesicles and endosomal compartments surrounded Hpa and Pi haustoria revealing differences between these two oomycetes, and suggesting a role for vesicle trafficking pathways for the pathogen-controlled biogenesis of the EHM. The latter is supported by enhanced susceptibility of mutants in endosome-mediated trafficking regulators. These observations point at host subcellular defences and specialization of the EHM in a pathogen-specific manner. Defence-associated haustorial encasements, a double-layered membrane that grows around mature haustoria, were frequently observed in Hpa interactions. Intriguingly, all tested plant proteins accumulated at Hpa haustorial encasements suggesting the general recruitment of default vesicle trafficking pathways to defend pathogen access. Altogether, our results show common requirements of subcellular changes associated with oomycete biotrophy, and highlight differences between two oomycete pathogens in reprogramming host cell vesicle trafficking for haustoria accommodation. This provides a framework for further dissection of the pathogen-triggered reprogramming of host subcellular changes. PMID:22233428

  6. Patterns of plant subcellular responses to successful oomycete infections reveal differences in host cell reprogramming and endocytic trafficking.

    PubMed

    Lu, Yi-Ju; Schornack, Sebastian; Spallek, Thomas; Geldner, Niko; Chory, Joanne; Schellmann, Swen; Schumacher, Karin; Kamoun, Sophien; Robatzek, Silke

    2012-05-01

    Adapted filamentous pathogens such as the oomycetes Hyaloperonospora arabidopsidis (Hpa) and Phytophthora infestans (Pi) project specialized hyphae, the haustoria, inside living host cells for the suppression of host defence and acquisition of nutrients. Accommodation of haustoria requires reorganization of the host cell and the biogenesis of a novel host cell membrane, the extrahaustorial membrane (EHM), which envelops the haustorium separating the host cell from the pathogen. Here, we applied live-cell imaging of fluorescent-tagged proteins labelling a variety of membrane compartments and investigated the subcellular changes associated with accommodating oomycete haustoria in Arabidopsis and N. benthamiana. Plasma membrane-resident proteins differentially localized to the EHM. Likewise, secretory vesicles and endosomal compartments surrounded Hpa and Pi haustoria revealing differences between these two oomycetes, and suggesting a role for vesicle trafficking pathways for the pathogen-controlled biogenesis of the EHM. The latter is supported by enhanced susceptibility of mutants in endosome-mediated trafficking regulators. These observations point at host subcellular defences and specialization of the EHM in a pathogen-specific manner. Defence-associated haustorial encasements, a double-layered membrane that grows around mature haustoria, were frequently observed in Hpa interactions. Intriguingly, all tested plant proteins accumulated at Hpa haustorial encasements suggesting the general recruitment of default vesicle trafficking pathways to defend pathogen access. Altogether, our results show common requirements of subcellular changes associated with oomycete biotrophy, and highlight differences between two oomycete pathogens in reprogramming host cell vesicle trafficking for haustoria accommodation. This provides a framework for further dissection of the pathogen-triggered reprogramming of host subcellular changes.

  7. Vector-Host Interactions Governing Epidemiology of West Nile Virus in Southern California

    PubMed Central

    Molaei, Goudarz; Cummings, Robert F.; Su, Tianyun; Armstrong, Philip M.; Williams, Greg A.; Cheng, Min-Lee; Webb, James P.; Andreadis, Theodore G.

    2010-01-01

    Southern California remains an important focus of West Nile virus (WNV) activity, with persistently elevated incidence after invasion by the virus in 2003 and subsequent amplification to epidemic levels in 2004. Eco-epidemiological studies of vectors-hosts-pathogen interactions are of paramount importance for better understanding of the transmission dynamics of WNV and other emerging mosquito-borne arboviruses. We investigated vector-host interactions and host-feeding patterns of 531 blood-engorged mosquitoes in four competent mosquito vectors by using a polymerase chain reaction (PCR) method targeting mitochondrial DNA to identify vertebrate hosts of blood-fed mosquitoes. Diagnostic testing by cell culture, real-time reverse transcriptase-PCR, and immunoassays were used to examine WNV infection in blood-fed mosquitoes, mosquito pools, dead birds, and mammals. Prevalence of WNV antibodies among wild birds was estimated by using a blocking enzyme-linked immunosorbent assay. Analyses of engorged Culex quinquefasciatus revealed that this mosquito species acquired 88.4% of the blood meals from avian and 11.6% from mammalian hosts, including humans. Similarly, Culex tarsalis fed 82% on birds and 18% on mammals. Culex erythrothorax fed on both birds (59%) and mammals (41%). In contrast, Culex stigmatosoma acquired all blood meals from avian hosts. House finches and a few other mostly passeriform birds served as the main hosts for the blood-seeking mosquitoes. Evidence of WNV infection was detected in mosquito pools, wild birds, dead birds, and mammals, including human fatalities during the study period. Our results emphasize the important role of house finches and several other passeriform birds in the maintenance and amplification of WNV in southern California, with Cx. quinquefasciatus acting as both the principal enzootic and “bridge vector” responsible for the spillover of WNV to humans. Other mosquito species, such as Cx. tarsalis and Cx. stigmatosoma, are

  8. Host parasite interactions in closed and open microbial cultivation system

    NASA Astrophysics Data System (ADS)

    Pisman, T. I.; Pechurkin, N. S.

    The study addresses interaction of bacteria and phages in the host parasite system in batch and continuous cultures. The study system consists of the auxotrophic strain of Brevibacterium Brevibacterium sp. 22L and the bacteriophage of Brevibacterium sp., isolated from the soil by the enrichment method.Closed system. In the investigation of the relationship between the time of bacterial lysis and multiplicity of phage infection it has been found that at a lower phage amount per cell it takes a longer time for the lysis of the culture to become discernible. Another important factor determining cytolysis in liquid medium is the physiological state of bacterial population. Specific growth rate of bacteria at the moment of phage infection has been chosen as an indicator of the physiological state of bacteria. It has been shown that the shortest latent period and the largest output of the phage are observed during the logarithmic growth phase of bacteria grown under favorable nutrient conditions. In the stationary phase, bacterial cells become “a bad host” for the phage, whose reproduction rate decreases, and the lysis either slows down significantly or does not occur at all.Open system. It has been found that in continuous culture, the components of the host parasite system can coexist over a long period of time. After phage infection, the sizes of the both populations vary for some time and then the density of the host population reaches the level close to that of the uninfected culture. The phage population copies the variations in the density of the host population, but in antiphase. It has been proven that the bacterium becomes resistant to the phage rather soon. It has been supposed that primary resistance is of physiological origin, because the percentage of cells that have survived lysis about 0.2% of the initial bacterial population is too high for phage-resistant mutants. Bacteria and phages cultured over extended periods of time in the host parasite system

  9. Burkholderia cenocepacia differential gene expression during host-pathogen interactions and adaptation to the host environment.

    PubMed

    O'Grady, Eoin P; Sokol, Pamela A

    2011-01-01

    Members of the Burkholderia cepacia complex (Bcc) are important in medical, biotechnological, and agricultural disciplines. These bacteria naturally occur in soil and water environments and have adapted to survive in association with plants and animals including humans. All Bcc species are opportunistic pathogens including Burkholderia cenocepacia that causes infections in cystic fibrosis and chronic granulomatous disease patients. The adaptation of B. cenocepacia to the host environment was assessed in a rat chronic respiratory infection model and compared to that of high cell-density in vitro grown cultures using transcriptomics. The distribution of genes differentially expressed on chromosomes 1, 2, and 3 was relatively proportional to the size of each genomic element, whereas the proportion of plasmid-encoded genes differentially expressed was much higher relative to its size and most genes were induced in vivo. The majority of genes encoding known virulence factors, components of types II and III secretion systems and chromosome 2-encoded type IV secretion system were similarly expressed between in vitro and in vivo environments. Lower expression in vivo was detected for genes encoding N-acyl-homoserine lactone synthase CepI, orphan LuxR homolog CepR2, zinc metalloproteases ZmpA and ZmpB, LysR-type transcriptional regulator ShvR, nematocidal protein AidA, and genes associated with flagellar motility, Flp type pilus formation, and type VI secretion. Plasmid-encoded type IV secretion genes were markedly induced in vivo. Additional genes induced in vivo included genes predicted to be involved in osmotic stress adaptation or intracellular survival, metal ion, and nutrient transport, as well as those encoding outer membrane proteins. Genes identified in this study are potentially important for virulence during host-pathogen interactions and may be associated with survival and adaptation to the host environment during chronic lung infections.

  10. Lectin Activation in Giardia lamblia by Host Protease: A Novel Host-Parasite Interaction

    NASA Astrophysics Data System (ADS)

    Lev, Boaz; Ward, Honorine; Keusch, Gerald T.; Pereira, Miercio E. A.

    1986-04-01

    A lectin in Giardia lamblia was activated by secretions from the human duodenum, the environment where the parasite lives. Incubation of the secretions with trypsin inhibitors prevented the appearance of lectin activity, implicating proteases as the activating agent. Accordingly, lectin activation was also produced by crystalline trypsin and Pronase; other proteases tested were ineffective. When activated, the lectin agglutinated intestinal cells to which the parasite adheres in vivo. The lectin was most specific to mannose-6-phosphate and apparently was bound to the plasma membrane. Activation of a parasite lectin by a host protease represents a novel mechanism of hostparasite interaction and may contribute to the affinity of Giardia lamblia to the infection site.

  11. Genomic RNAi screening in Drosophila S2 cells: What have we learned about host-pathogen interactions?

    PubMed Central

    Cherry, Sara

    2008-01-01

    The détente between pathogen and host has been of keen interest to researchers in spite of being exceedingly difficult to probe. Recently, new RNA interference (RNAi) technologies, in particular in Drosophila tissue culture cells, have made it possible to interrogate the genetics of host organisms rapidly, with nearly complete genomic coverage and high fidelity. Therefore, it is not surprising that the applications of RNAi to the study of host-pathogen interactions were amongst the first to be published, and have already revealed many new insights into the hosts’ role in infection. This review will highlight the application of RNAi screening to pathogen-host interactions in Drosophila cells and will reveal some of the lessons learned from this approach. PMID:18539520

  12. Human colorectal mucosal microbiota correlates with its host niche physiology revealed by endomicroscopy

    PubMed Central

    Wang, Ai-Hua; Li, Ming; Li, Chang-Qing; Kou, Guan-Jun; Zuo, Xiu-Li; Li, Yan-Qing

    2016-01-01

    The human gut microbiota plays a pivotal role in the maintenance of health, but how the microbiota interacts with the host at the colorectal mucosa is poorly understood. We proposed that confocal laser endomicroscopy (CLE) might help to untangle this relationship by providing in vivo physiological information of the mucosa. We used CLE to evaluate the in vivo physiology of human colorectal mucosa, and the mucosal microbiota was quantified using 16 s rDNA pyrosequencing. The human mucosal microbiota agglomerated to three major clusters dominated by Prevotella, Bacteroides and Lactococcus. The mucosal microbiota clusters did not significantly correlate with the disease status or biopsy sites but closely correlated with the mucosal niche physiology, which was non-invasively revealed by CLE. Inflammation tilted two subnetworks within the mucosal microbiota. Infiltration of inflammatory cells significantly correlated with multiple components in the predicted metagenome, such as the VirD2 component of the type IV secretory pathway. Our data suggest that a close correlation exists between the mucosal microbiota and the colorectal mucosal physiology, and CLE is a clinically available tool that can be used to facilitate the study of the in vivo correlation between colorectal mucosal physiology and the mucosal microbiota. PMID:26916597

  13. Comparative Secretome Analysis Reveals Perturbation of Host Secretion Pathways by a Hypovirus

    PubMed Central

    Wang, Jinzi; Shi, Liming; He, Xipu; Lu, Lidan; Li, Xiaoping; Chen, Baoshan

    2016-01-01

    To understand the impact of a hypovirus infection on the secretome of the chestnut blight fungus, Cryphonectria parasitica, a phytopathogenic filamentous fungus, two-dimensional electrophoresis (2-DE) and isobaric tag for relative and absolute quantitation (iTRAQ) technology were employed to identify and quantify the secreted proteins. A total of 403 unique proteins were identified from the secretome of the wild type virus-free strain EP155. Of these proteins, 329 were predicted to be involved in known secretory pathways and they are primarily composed of metabolic enzymes, biological regulators, responders to stimulus and components involved in plant-pathogen interactions. When infected with the hypovirus CHV1-EP713, 99 proteins were found to be differentially expressed as compared to the wild type strain EP155. These proteins were mainly related to plant cell wall degradation, response to host defense, fungal virulence and intracellular structure. The effects of CHV1 on secreted proteins may reveal a relationship between physiological pathways and hypovirulence. PMID:27698384

  14. Individual Apostichopus japonicus fecal microbiome reveals a link with polyhydroxybutyrate producers in host growth gaps.

    PubMed

    Yamazaki, Yohei; Meirelles, Pedro Milet; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Thompson, Fabiano L; Sakai, Yuichi; Sawabe, Toko; Sawabe, Tomoo

    2016-02-24

    Gut microbiome shapes various aspects of a host's physiology, but these functions in aquatic animal hosts have yet to be fully investigated. The sea cucumber Apostichopus japonicus Selenka is one such example. The large growth gap in their body size has delayed the development of intensive aquaculture, nevertheless the species is in urgent need of conservation. To understand possible contributions of the gut microbiome to its host's growth, individual fecal microbiome comparisons were performed. High-throughput 16S rRNA sequencing revealed significantly different microbiota in larger and smaller individuals; Rhodobacterales in particular was the most significantly abundant bacterial group in the larger specimens. Further shotgun metagenome of representative samples revealed a significant abundance of microbiome retaining polyhydroxybutyrate (PHB) metabolism genes in the largest individual. The PHB metabolism reads were potentially derived from Rhodobacterales. These results imply a possible link between microbial PHB producers and potential growth promotion in Deuterostomia marine invertebrates.

  15. Varied interactions between proviruses and adjacent host chromatin.

    PubMed Central

    Conklin, K F; Groudine, M

    1986-01-01

    Retroviruses integrated at unique locations in the host genome can be expressed at different levels. We have analyzed the preintegration sites of three transcriptionally competent avian endogenous proviruses (evs) to determine whether the various levels of provirus expression correlate with their location in active or inactive regions of chromatin. Our results show that in three of four cell types, the chromatin conformation (as defined by relative nuclease sensitivity) of virus preintegration sites correlates with the level of expression of the resident provirus in ev+ cells: two inactive proviruses (ev-1 and ev-2) reside in nuclease-resistant chromatin domains and one active provirus (ev-3) resides in a nuclease-sensitive domain. Nuclear runoff transcription assays reveal that the preintegration sites of the active and inactive viruses are not transcribed. However, in erythrocytes of 15-day-old chicken embryos (15d RBCs), the structure and activity of the ev-3 provirus is independent of the conformation of its preintegration site. In this cell type, the ev-3 preintegration site is organized in a nuclease-resistant conformation, while the ev-3 provirus is in a nuclease-sensitive conformation and is transcribed. In addition, the nuclease sensitivity of host sequences adjacent to ev-3 is altered in ev-3+ 15d RBCs relative to that found in 15d RBCs that lack ev-3. These data suggest that the relationship between preintegration site structure and retrovirus expression is more complex than previously described. Images PMID:3025623

  16. Host-Pathogen Interactions Made Transparent with the Zebrafish Model

    PubMed Central

    Meijer, Annemarie H; Spaink, Herman P

    2011-01-01

    The zebrafish holds much promise as a high-throughput drug screening model for immune-related diseases, including inflammatory and infectious diseases and cancer. This is due to the excellent possibilities for in vivo imaging in combination with advanced tools for genomic and large scale mutant analysis. The context of the embryo’s developing immune system makes it possible to study the contribution of different immune cell types to disease progression. Furthermore, due to the temporal separation of innate immunity from adaptive responses, zebrafish embryos and larvae are particularly useful for dissecting the innate host factors involved in pathology. Recent studies have underscored the remarkable similarity of the zebrafish and human immune systems, which is important for biomedical applications. This review is focused on the use of zebrafish as a model for infectious diseases, with emphasis on bacterial pathogens. Following a brief overview of the zebrafish immune system and the tools and methods used to study host-pathogen interactions in zebrafish, we discuss the current knowledge on receptors and downstream signaling components that are involved in the zebrafish embryo’s innate immune response. We summarize recent insights gained from the use of bacterial infection models, particularly the Mycobacterium marinum model, that illustrate the potential of the zebrafish model for high-throughput antimicrobial drug screening. PMID:21366518

  17. Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host.

    PubMed

    Leontovyč, Roman; Young, Neil D; Korhonen, Pasi K; Hall, Ross S; Tan, Patrick; Mikeš, Libor; Kašný, Martin; Horák, Petr; Gasser, Robin B

    2016-02-01

    To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes) of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts' immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes.

  18. Workshop on Spaceflight Alterations in Host-Microorganism Interactions

    NASA Technical Reports Server (NTRS)

    Ott, C. Mark

    2010-01-01

    On June 11, 2009, a workshop that included internal and external experts was convened to determine the risk of changes in microorganisms that could alter host-microorganism interactions during a mission. The evidence is based in part on multiple flight experiments which indicate altered virulence in Salmonella typhimurium when cultured in flight. The workshop participants were tasked to determine if adequate information was available to initiate changes in NASA's current approach to infectious disease risk assessment and medical operations. The consensus of the participants is that the current evidence was not adequate to provide direction for operational changes; however, the evidence is compelling and clearly indicates that changes to microorganisms were occurring during spaceflight and further research is required.

  19. Interactions of legionella effector proteins with host phosphoinositide lipids.

    PubMed

    Weber, Stephen; Dolinsky, Stephanie; Hilbi, Hubert

    2013-01-01

    By means of the Icm/Dot type IV secretion system Legionella pneumophila translocates several effector proteins into host cells, where they anchor to the cytoplasmic face of the LCV membrane by binding to phosphoinositide (PI) lipids. Thus, phosphatidylinositol-4-phosphate anchors the effector proteins SidC and SidM, which promote the interaction of LCVs with the ER and the secretory vesicle trafficking -pathway. In this chapter, we describe protocols to (1) identify PI-binding proteins in Legionella lysates using PI-beads, (2) determine PI-binding specificities and affinities of recombinant Legionella effector proteins by protein-lipid overlays, and (3) use Legionella effectors to identify cellular PI lipids.

  20. Disentangling AGN-Host Galaxy Interactions with Chandra

    NASA Astrophysics Data System (ADS)

    Wang, Junfeng

    2014-11-01

    The circum-nuclear region in active galaxies is often complex with presence of high excitation gas, collimated radio outflow, and star forming regions, besides the active central supermassive black hole. In Chandra studies of a number of archetypal Seyfert galaxies to investigate AGN-host galaxy interaction, we were able to evaluate the mass outflow rate and shock heating by radio jet. For galaxies in the throes of a violent merging event such as NGC6240, we were able to resolve 70MK hot gas surrounding the double nuclei and discovered a large scale soft X-ray halo. The unique resolving power of Chandra also enables more discovery of such dual AGN systems and signs of past AGN outburst activities.

  1. Genetic and environmental control of host-gut microbiota interactions

    PubMed Central

    Org, Elin; Parks, Brian W.; Joo, Jong Wha J.; Emert, Benjamin; Schwartzman, William; Kang, Eun Yong; Mehrabian, Margarete; Pan, Calvin; Knight, Rob; Gunsalus, Robert; Drake, Thomas A.; Eskin, Eleazar; Lusis, Aldons J.

    2015-01-01

    Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high-resolution association mapping. Using a SNP-based approach with a linear mixed model, we estimated the heritability of microbiota composition. We conclude that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high-fat, high-sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, A×B19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain A×B19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host-microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publicly available data provide a resource for future studies. PMID:26260972

  2. Genetics of host-pathogen interactions in the wheat-Stagonospora nodorum pathosystem

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stagonospora nodorum causes the disease Stagonospora nodorum blotch (SNB) in wheat. S. nodorum produces numerous host-selective toxins (HSTs), all of which interact with dominant host sensitivity genes to cause disease. These host-toxin interactions are mirror images of classical gene-for-gene inter...

  3. VirHostNet 2.0: surfing on the web of virus/host molecular interactions data

    PubMed Central

    Guirimand, Thibaut; Delmotte, Stéphane; Navratil, Vincent

    2015-01-01

    VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated to the network-based exploration of virus–host protein–protein interactions. Since the previous VirhostNet release (2009), a second run of manual curation was performed to annotate the new torrent of high-throughput protein–protein interactions data from the literature. This resource is shared publicly, in PSI-MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet 2.0 is based on Cytoscape web library and provides a user-friendly access to the most complete and accurate resource of virus–virus and virus–host protein–protein interactions as well as their projection onto their corresponding host cell protein interaction networks. We hope that the VirHostNet 2.0 system will facilitate systems biology and gene-centered analysis of infectious diseases and will help to identify new molecular targets for antiviral drugs design. This resource will also continue to help worldwide scientists to improve our knowledge on molecular mechanisms involved in the antiviral response mediated by the cell and in the viral strategies selected by viruses to hijack the host immune system. PMID:25392406

  4. VirHostNet 2.0: surfing on the web of virus/host molecular interactions data.

    PubMed

    Guirimand, Thibaut; Delmotte, Stéphane; Navratil, Vincent

    2015-01-01

    VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated to the network-based exploration of virus-host protein-protein interactions. Since the previous VirhostNet release (2009), a second run of manual curation was performed to annotate the new torrent of high-throughput protein-protein interactions data from the literature. This resource is shared publicly, in PSI-MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet 2.0 is based on Cytoscape web library and provides a user-friendly access to the most complete and accurate resource of virus-virus and virus-host protein-protein interactions as well as their projection onto their corresponding host cell protein interaction networks. We hope that the VirHostNet 2.0 system will facilitate systems biology and gene-centered analysis of infectious diseases and will help to identify new molecular targets for antiviral drugs design. This resource will also continue to help worldwide scientists to improve our knowledge on molecular mechanisms involved in the antiviral response mediated by the cell and in the viral strategies selected by viruses to hijack the host immune system.

  5. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

    PubMed Central

    Viktorovskaya, Olga V.; Greco, Todd M.; Cristea, Ileana M.; Thompson, Sunnie R.

    2016-01-01

    Background There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. Methodology/Principal Findings Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. Conclusions/Significance The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with

  6. High richness of ectomycorrhizal fungi and low host specificity in a coastal sand dune ecosystem revealed by network analysis.

    PubMed

    Roy-Bolduc, Alice; Laliberté, Etienne; Hijri, Mohamed

    2016-01-01

    Ectomycorrhizal (EM) fungi are ubiquitous in temperate and boreal forests, comprising over 20,000 species forming root symbiotic associations with Pinaceae and woody angiosperms. As much as 100 different EM fungal species can coexist and interact with the same tree species, forming complex multispecies networks in soils. The degree of host specificity and structural properties of these interaction networks (e.g., nestedness and modularity) may influence plant and fungal community assembly and species coexistence, yet their structure has been little studied in northern coniferous forests, where trees depend on EM fungi for nutrient acquisition. We used high-throughput sequencing to characterize the composition and diversity of bulk soil and root-associated fungal communities in four co-occurring Pinaceae in a relic foredune plain located at Îles de la Madeleine, Québec, Canada. We found high EM fungal richness across the four hosts, with a total of 200 EM operational taxonomic units (OTUs), mainly belonging to the Agaricomycetes. Network analysis revealed an antinested pattern in both bulk soil and roots EM fungal communities. However, there was no detectable modularity (i.e., subgroups of interacting species) in the interaction networks, indicating a low level of specificity in these EM associations. In addition, there were no differences in EM fungal OTU richness or community structure among the four tree species. Limited shared resources and competitive exclusion typically restrict the number of taxa coexisting within the same niche. As such, our finding of high EM fungal richness and low host specificity highlights the need for further studies to determine the mechanisms enabling such a large number of EM fungal species to coexist locally on the same hosts.

  7. Parasite transmission in social interacting hosts: Monogenean epidemics in guppies

    USGS Publications Warehouse

    Johnson, M.B.; Lafferty, K.D.; van, Oosterhout C.; Cable, J.

    2011-01-01

    Background: Infection incidence increases with the average number of contacts between susceptible and infected individuals. Contact rates are normally assumed to increase linearly with host density. However, social species seek out each other at low density and saturate their contact rates at high densities. Although predicting epidemic behaviour requires knowing how contact rates scale with host density, few empirical studies have investigated the effect of host density. Also, most theory assumes each host has an equal probability of transmitting parasites, even though individual parasite load and infection duration can vary. To our knowledge, the relative importance of characteristics of the primary infected host vs. the susceptible population has never been tested experimentally. Methodology/Principal Findings: Here, we examine epidemics using a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia reticulata). Hosts were maintained at different densities (3, 6, 12 and 24 fish in 40 L aquaria), and we monitored gyrodactylids both at a population and individual host level. Although parasite population size increased with host density, the probability of an epidemic did not. Epidemics were more likely when the primary infected fish had a high mean intensity and duration of infection. Epidemics only occurred if the primary infected host experienced more than 23 worm days. Female guppies contracted infections sooner than males, probably because females have a higher propensity for shoaling. Conclusions/Significance: These findings suggest that in social hosts like guppies, the frequency of social contact largely governs disease epidemics independent of host density. ?? 2011 Johnson et al.

  8. Parasite transmission in social interacting hosts: Monogenean epidemics in guppies

    USGS Publications Warehouse

    Johnson, Mirelle B.; Lafferty, Kevin D.; van Oosterhout, Cock; Cable, Joanne

    2011-01-01

    Background Infection incidence increases with the average number of contacts between susceptible and infected individuals. Contact rates are normally assumed to increase linearly with host density. However, social species seek out each other at low density and saturate their contact rates at high densities. Although predicting epidemic behaviour requires knowing how contact rates scale with host density, few empirical studies have investigated the effect of host density. Also, most theory assumes each host has an equal probability of transmitting parasites, even though individual parasite load and infection duration can vary. To our knowledge, the relative importance of characteristics of the primary infected host vs. the susceptible population has never been tested experimentally. Methodology/Principal Findings Here, we examine epidemics using a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia reticulata). Hosts were maintained at different densities (3, 6, 12 and 24 fish in 40 L aquaria), and we monitored gyrodactylids both at a population and individual host level. Although parasite population size increased with host density, the probability of an epidemic did not. Epidemics were more likely when the primary infected fish had a high mean intensity and duration of infection. Epidemics only occurred if the primary infected host experienced more than 23 worm days. Female guppies contracted infections sooner than males, probably because females have a higher propensity for shoaling. Conclusions/Significance These findings suggest that in social hosts like guppies, the frequency of social contact largely governs disease epidemics independent of host density.

  9. Host - hepatitis C viral interactions: The role of genetics.

    PubMed

    Heim, Markus H; Bochud, Pierre-Yves; George, Jacob

    2016-10-01

    Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.

  10. Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host

    PubMed Central

    Leontovyč, Roman; Young, Neil D.; Korhonen, Pasi K.; Hall, Ross S.; Tan, Patrick; Mikeš, Libor; Kašný, Martin; Horák, Petr; Gasser, Robin B.

    2016-01-01

    To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes) of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts’ immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes. PMID:26863542

  11. Interrogation of infected hepatocyte signaling reveals that suppression of host p53 is critical for Plasmodium liver stage infection

    PubMed Central

    Kaushansky, Alexis; Ye, Albert S.; Austin, Laura S.; Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Camargo, Nelly; Metzger, Peter G.; Douglass, Alyse N.; MacBeath, Gavin; Kappe, Stefan H.I.

    2013-01-01

    Summary Plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. Analysis of host signaling pathways affected by liver stage infection could provide critical insights into host-pathogen interactions and reveal targets for intervention. Using protein lysate microarrays we found that Plasmodium yoelii rodent malaria parasites perturb hepatocyte regulatory pathways involved in cell survival, proliferation and autophagy. Notably, the pro-death protein p53 was substantially decreased in infected hepatocytes, suggesting it could be targeted by the parasite to foster survival. Indeed, mice that express increased levels of p53 showed reduced liver stage parasite burden whereas p53 knockout mice suffered increased liver stage burden. Furthermore, boosting p53 levels using the small molecule Nutlin-3 dramatically reduced liver stage burden in vitro and in vivo. We conclude that perturbation of the hepatocyte p53 pathway critically impacts parasite survival. Thus, host pathways might constitute potential targets for host-based antimalarial prophylaxis. PMID:23478020

  12. Host-parasite interactions: Marine bivalve molluscs and protozoan parasites, Perkinsus species.

    PubMed

    Soudant, Philippe; E Chu, Fu-Lin; Volety, Aswani

    2013-10-01

    This review assesses and examines the work conducted to date concerning host and parasite interactions between marine bivalve molluscs and protozoan parasites, belonging to Perkinsus species. The review focuses on two well-studied host-parasite interaction models: the two clam species, Ruditapes philippinarum and R. decussatus, and the parasite Perkinsus olseni, and the eastern oyster, Crassostrea virginica, and the parasite Perkinsus marinus. Cellular and humoral defense responses of the host in combating parasitic infection, the mechanisms (e.g., antioxidant enzymes, extracellular products) employed by the parasite in evading host defenses as well as the role of environmental factors in modulating the host-parasite interactions are described.

  13. Differential Communications between Fungi and Host Plants Revealed by Secretome Analysis of Phylogenetically Related Endophytic and Pathogenic Fungi

    PubMed Central

    Xu, Xihui; He, Qin; Zhang, Chulong

    2016-01-01

    During infection, both phytopathogenic and endophytic fungi form intimate contact with living plant cells, and need to resist or disable host defences and modify host metabolism to adapt to their host. Fungi can achieve these changes by secreting proteins and enzymes. A comprehensive comparison of the secretomes of both endophytic and pathogenic fungi can improve our understanding of the interactions between plants and fungi. Although Magnaporthe oryzae, Gaeumannomyces graminis, and M. poae are economically important fungal pathogens, and the related species Harpophora oryzae is an endophyte, they evolved from a common pathogenic ancestor. We used a pipeline analysis to predict the H. oryzae, M. oryzae, G. graminis, and M. poae secretomes and identified 1142, 1370, 1001, and 974 proteins, respectively. Orthologue gene analyses demonstrated that the M. oryzae secretome evolved more rapidly than those of the other three related species, resulting in many species-specific secreted protein-encoding genes, such as avirulence genes. Functional analyses highlighted the abundance of proteins involved in the breakdown of host plant cell walls and oxidation-reduction processes. We identified three novel motifs in the H. and M. oryzae secretomes, which may play key roles in the interaction between rice and H. oryzae. Furthermore, we found that expression of the H. oryzae secretome involved in plant cell wall degradation was downregulated, but the M. oryzae secretome was upregulated with many more upregulated genes involved in oxidation-reduction processes. The divergent in planta expression patterns of the H. and M. oryzae secretomes reveal differences that are associated with mutualistic and pathogenic interactions, respectively. PMID:27658302

  14. Emerging functions as host cell factors - an encyclopedia of annexin-pathogen interactions.

    PubMed

    Kuehnl, Alexander; Musiol, Agnes; Raabe, Carsten A; Rescher, Ursula

    2016-10-01

    Emerging infectious diseases and drug-resistant infectious agents call for the development of innovative antimicrobial strategies. With pathogenicity now considered to arise from the complex and bi-directional interplay between a microbe and the host, host cell factor targeting has emerged as a promising approach that might overcome the limitations of classical antimicrobial drug development and could open up novel and efficient therapeutic strategies. Interaction with and modulation of host cell membranes is a recurrent theme in the host-microbe relationship. In this review, we provide an overview of what is currently known about the role of the Ca2+ dependent, membrane-binding annexin protein family in pathogen-host interactions, and discuss their emerging functions as host cell derived auxiliary proteins in microbe-host interactions and host cell targets.

  15. Infectious diseases of marine molluscs and host responses as revealed by genomic tools

    PubMed Central

    Ford, Susan E.

    2016-01-01

    More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance. PMID:26880838

  16. Infectious diseases of marine molluscs and host responses as revealed by genomic tools.

    PubMed

    Guo, Ximing; Ford, Susan E

    2016-03-05

    More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance.

  17. A meta-metabolome network of carbohydrate metabolism: interactions between gut microbiota and host.

    PubMed

    Ibrahim, Maziya; Anishetty, Sharmila

    2012-11-16

    With the current knowledge of the multitude of microbes that inhabit the human body, it is increasingly clear that they constitute an integral component of the host. The gut microbiota community is principally involved in the metabolism of dietary constituents such as carbohydrates which account for majority of the energy intake from diet. Diet has gained an important role in shaping the composition of gut inhabitants. The quantity and type of food consumed is recognized as a causal factor for metabolic disorders such as obesity and diabetes. Analysis of host-microbe interactions can thus contribute to the understanding of such metabolic disorders. In this study, data from Kyoto Encyclopedia of Genes and Genomes and Carbohydrate Active EnZYmes Database was utilized as a starting point. Enzyme information from the host Homo sapiens coupled with details of the three predominant phyla of gut bacteria, namely Firmicutes, Bacteroidetes and Actinobacteria were used in the creation of a comprehensive metabolic network, which we refer to as 'meta-metabolome'. This 'meta-metabolome' provides a perspective of the degree to which microbes influence carbohydrate metabolism, in conjunction with host specific enzymes. Analysis of reactions in the network reveals the amplification of monosaccharide content brought about by microbial enzyme activity. The framework outlined in this study provides a holistic approach to assess host-microbe symbiosis. It also provides us with a means of analyzing how diet can be modulated to provide beneficial effects to the host or how probiotics can potentially be used to relieve certain metabolic disorders.

  18. Engineering the AAV capsid to optimize vector-host-interactions.

    PubMed

    Büning, Hildegard; Huber, Anke; Zhang, Liang; Meumann, Nadja; Hacker, Ulrich

    2015-10-01

    Adeno-associated viral (AAV) vectors are the most widely used delivery system for in vivo gene therapy. Vectors developed from natural AAV isolates achieved clinical benefit for a number of patients suffering from monogenetic disorders. However, high vector doses were required and the presence of pre-existing neutralizing antibodies precluded a number of patients from participation. Further challenges are related to AAV's tropism that lacks cell type selectivity resulting in off-target transduction. Conversely, specific cell types representing important targets for gene therapy like stem cells or endothelial cells show low permissiveness. To overcome these limitations, elegant rational design- as well as directed evolution-based strategies were developed to optimize various steps of AAV's host interaction. These efforts resulted in next generation vectors with enhanced capabilities, that is increased efficiency of cell transduction, targeted transduction of previously non-permissive cell types, escape from antibody neutralization and off-target free in vivo delivery of vector genomes. These important achievements are expected to improve current and pave the way towards novel AAV-based applications in gene therapy and regenerative medicine.

  19. Host-microbiota interactions within the fish intestinal ecosystem.

    PubMed

    Pérez, T; Balcázar, J L; Ruiz-Zarzuela, I; Halaihel, N; Vendrell, D; de Blas, I; Múzquiz, J L

    2010-07-01

    Teleost fish are in direct contact with the aquatic environment, and are therefore in continual contact with a complex and dynamic microbiota, some of which may have implications for health. Mucosal surfaces represent the main sites in which environmental antigens and intestinal microbiota interact with the host. Thus, the gut-associated lymphoid tissues (GALT) must develop mechanisms to discriminate between pathogenic and commensal microorganisms. Colonization of intestinal mucosal surfaces with a normal microbiota has a positive effect on immune regulatory functions of the gut, and disturbance in these immune regulatory functions by an imbalanced microbiota may contribute to the development of diseases. Significant attention has therefore been recently focused on the role of probiotics in the induction or restoration of a disturbed microbiota to its normal beneficial composition. Given this, this article explores the fascinating relationship between the fish immune system and the bacteria that are present in its intestinal microbiota, focusing on the bacterial effect on the development of certain immune responses.

  20. Role of Sex Steroid Hormones in Bacterial-Host Interactions

    PubMed Central

    García-Gómez, Elizabeth; González-Pedrajo, Bertha; Camacho-Arroyo, Ignacio

    2013-01-01

    Sex steroid hormones play important physiological roles in reproductive and nonreproductive tissues, including immune cells. These hormones exert their functions by binding to either specific intracellular receptors that act as ligand-dependent transcription factors or membrane receptors that stimulate several signal transduction pathways. The elevated susceptibility of males to bacterial infections can be related to the usually lower immune responses presented in males as compared to females. This dimorphic sex difference is mainly due to the differential modulation of the immune system by sex steroid hormones through the control of proinflammatory and anti-inflammatory cytokines expression, as well as Toll-like receptors (TLRs) expression and antibody production. Besides, sex hormones can also affect the metabolism, growth, or virulence of pathogenic bacteria. In turn, pathogenic, microbiota, and environmental bacteria are able to metabolize and degrade steroid hormones and their related compounds. All these data suggest that sex steroid hormones play a key role in the modulation of bacterial-host interactions. PMID:23509808

  1. Host-microbe interactions via membrane transport systems.

    PubMed

    Konishi, Hiroaki; Fujiya, Mikihiro; Kohgo, Yutaka

    2015-04-01

    Living organisms take in essential molecules and get rid of wastes effectively through the selective transport of materials. Especially in the digestive tract, advanced transport systems are indispensable for the absorption of nutrients and elimination of waste products. These transport pathways control physiological functions by modulating the ionic environment inside and outside the cells. Moreover, recent studies have shown the importance of the expression of trafficking-related molecules and the population of gut microbiota. We found that the molecules secreted from microorganisms are imported into the cells via transporters or endocytosis and that they activate cell survival pathways of intestinal epithelial cells. These findings indicate that the interactions between the gut microbiota and host cells are mediated, at least partly, by the membrane transport systems. In addition, it is well known that the breakdown of transport systems induces various diseases. This review highlights the significance of the transport systems as the pathogenic molecules and therapeutic targets in gastrointestinal disorders. For example, abnormal expression of the genes encoding membrane transport-related molecules is frequently involved in digestive diseases, such as colorectal cancer and inflammatory bowel disease. We herein review the significance of these molecules as pathogenic and therapeutic targets for digestive diseases.

  2. Interaction Between Belonolaimus longicaudatus and Helicotylenchus pseudorobustus on Bermudagrass and Seashore Paspalum Hosts

    PubMed Central

    Crow, William T.; Luc, John E.; Sekora, Nicholas S.; Pang, Wenjing

    2013-01-01

    Belonolaimus longicaudatus and Helicotylenchus pseudorobustus are among the most common nematode parasites of turfgrasses in Florida. Bermudagrass (Cynodon dactylon × C. transvaalensis) and seashore paspalum (Paspalum vaginatum) are the two turf species most commonly used on Florida golf courses. This paper explores the interactions between B. longicaudatus and H. pseudorobustus on bermudagrass and seashore paspalum hosts. Data collected from thousands of nematode samples submitted to the Florida Nematode Assay Lab over a 8-yr period revealed a negative relationship between B. longicaudatus and H. pseudorobustus on bermudagrass, but not seashore paspalum. In a multi-year field plot experiment using multiple cultivars of bermudagrass, and seashore paspalum B. longicaudatus and H. pseudorobustus were negatively related on both turf species. Greenhouse trials where multiple cultivars of both turf species were inoculated with different combinations of B. longicaudatus and H. pseudorobustus found that each nematode species was inhibitory to the other on both host species. Belonolaimus longicaudatus and H. pseudorobustus clearly impact each other on turfgrass hosts, although the mechanism of the nematode-nematode interactions is unknown. PMID:23589655

  3. Proteomic profiling of host-biofilm interactions in an oral infection model resembling the periodontal pocket

    PubMed Central

    Bao, Kai; Belibasakis, Georgios N.; Selevsek, Nathalie; Grossmann, Jonas; Bostanci, Nagihan

    2015-01-01

    Periodontal infections cause inflammatory destruction of the tooth supporting tissues. We recently developed a dynamic, in vitro periodontal organotypic tissue model in a perfusion bioreactor system, in co-culture with an 11-species subgingival biofilm, which may recapitulate early events during the establishment of periodontal infections. This study aimed to characterize the global proteome regulations in this host-biofilm interaction model. Semi-quantitative shotgun proteomics were applied for protein identification and quantification in the co-culture supernatants (human and bacterial) and the biofilm lysates (bacterial). A total of 896 and 3363 proteins were identified as secreted in the supernatant and expressed in the biofilm lysate, respectively. Enriched gene ontology analysis revealed that the regulated secreted human tissue proteins were related to processes of cytoskeletal rearrangement, stress responses, apoptosis, and antigen presentation, all of which are commensurate with deregulated host responses. Most secreted bacterial biofilm proteins derived from their cytoplasmic domain. In the presence of the tissue, the levels of Fusobacterium nucleatum, Actinomyces oris and Campylobacter rectus proteins were significantly regulated. The functions of the up-regulated intracellular (biofilm lysate) proteins were associated with cytokinesis. In conclusion, the proteomic overview of regulated pathways in this host-biofilm interaction model provides insights to the early events of periodontal pathogenesis. PMID:26525412

  4. [Genome virology: the novel interaction of RNA viruses and host genomes].

    PubMed

    Tomonaga, Keizo

    2012-06-01

    The origin of virus-like organisms probably dates back to the earliest forms of cellular life. Such a long coexistence between viruses and ourselves suggests that viruses may have crucially influenced the evolution of our species and vice versa. Sequences derived from retroviruses and retrotransposons have been shown to make up a substantial part of the human genome, suggesting a direct role of virus infection as a source of new genetic information and genomic innovation of the host species. Until very recently, retroviruses were the only viruses known to generate such endogenous copies in vertebrate genomes. However, we and others have reported recently that non-retroviral RNA viruses, including bornaviruses and filoviruses, have been endogenized repeatedly during mammalian evolution. These endogenous elements of RNA viruses not only provide evidence of ancient viral infections in each animal species but also offer novel paradigms for the interaction between RNA viruses and their hosts. Based on the presentation of the plenary lecture at the XV International Congress of Virology 2011, I will review here our recent findings regarding the generation and functions of endogenous bornavirus-like N elements in mammalian genomes, in order to reveal the unknown dynamics of RNA viruses in eukaryotic cells, and also discuss the evolutionary interaction between RNA viruses and hosts.

  5. Disease dynamics in a coupled cholera model linking within-host and between-host interactions.

    PubMed

    Wang, Xueying; Wang, Jin

    2016-09-19

    A new modelling framework is proposed to study the within-host and between-host dynamics of cholera, a severe intestinal infection caused by the bacterium Vibrio cholerae. The within-host dynamics are characterized by the growth of highly infectious vibrios inside the human body. These vibrios shed from humans contribute to the environmental bacterial growth and the transmission of the disease among humans, providing a link from the within-host dynamics at the individual level to the between-host dynamics at the population and environmental level. A fast-slow analysis is conducted based on the two different time scales in our model. In particular, a bifurcation study is performed, and sufficient and necessary conditions are derived that lead to a backward bifurcation in cholera epidemics. Our result regarding the backward bifurcation highlights the challenges in the prevention and control of cholera.

  6. Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease

    PubMed Central

    Klughammer, Johanna; Dittrich, Marcus; Blom, Jochen; Mitesser, Vera; Vogel, Ulrich; Frosch, Matthias; Goesmann, Alexander; Müller, Tobias

    2017-01-01

    Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo. PMID:28081260

  7. Virus-host interactions: new insights from the small RNA world

    PubMed Central

    Browne, Edward P; Li, Junjie; Chong, Mark; Littman, Dan R

    2005-01-01

    RNA silencing has a known role in the antiviral responses of plants and insects. Recent evidence, including the finding that the Tat protein of human immunodeficiency virus (HIV) can suppress the host's RNA-silencing pathway and may thus counteract host antiviral RNAs, suggests that RNA-silencing pathways could also have key roles in mammalian virus-host interactions. PMID:16277756

  8. Genetic analysis of host-toxin interactions in the wheat-Stagonospora nodorum pathosystem

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stagonospora nodorum, causal agent of Stagonospora nodorum blotch (SNB) in wheat, produces multiple necrosis-inducing host-selective toxins (HSTs) that interact with dominant host sensitivity genes to cause disease. Absence of either the toxin or the dominant host gene precludes recognition and resu...

  9. Interactions of Seedborne Bacterial Pathogens with Host and Non-Host Plants in Relation to Seed Infestation and Seedling Transmission

    PubMed Central

    Dutta, Bhabesh; Gitaitis, Ronald; Smith, Samuel; Langston, David

    2014-01-01

    The ability of seed-borne bacterial pathogens (Acidovorax citrulli, Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato, Xanthomonas euvesicatoria, and Pseudomonas syringae pv. glycinea) to infest seeds of host and non-host plants (watermelon, tomato, pepper, and soybean) and subsequent pathogen transmission to seedlings was investigated. A non-pathogenic, pigmented strain of Serratia marcescens was also included to assess a null-interacting situation with the same plant species. Flowers of host and non-host plants were inoculated with 1×106 colony forming units (CFUs)/flower for each bacterial species and allowed to develop into fruits or umbels (in case of onion). Seeds harvested from each host/non-host bacterial species combination were assayed for respective bacteria by plating on semi-selective media. Additionally, seedlots for each host/non-host bacterial species combination were also assayed for pathogen transmission by seedling grow-out (SGO) assays under greenhouse conditions. The mean percentage of seedlots infested with compatible and incompatible pathogens was 31.7 and 30.9% (by plating), respectively and they were not significantly different (P = 0.67). The percentage of seedlots infested with null-interacting bacterial species was 16.8% (by plating) and it was significantly lower than the infested lots generated with compatible and incompatible bacterial pathogens (P = 0.03). None of the seedlots with incompatible/null-interacting bacteria developed symptoms on seedlings; however, when seedlings were assayed for epiphytic bacterial presence, 19.5 and 9.4% of the lots were positive, respectively. These results indicate that the seeds of non-host plants can become infested with incompatible and null-interacting bacterial species through flower colonization and they can be transmitted via epiphytic colonization of seedlings. In addition, it was also observed that flowers and seeds of non-host plants can be colonized

  10. Role of MicroRNAs in Insect Host-Microorganism Interactions.

    PubMed

    Asgari, Sassan

    2011-01-01

    MicroRNAs (miRNAs) have appeared as important regulators of various biological processes including development, cancer, immunity, and host-microorganism interactions. Accumulating evidence demonstrates the differential expression of host miRNAs upon infection by various microorganisms and the involvement of microorganism-encoded miRNAs in host manipulation. Some of these alterations could be part of a host response to an infection to limit replication and dissemination of the microorganism or, conversely, due to manipulation of the host miRNA pathway by the microorganism to facilitate its replication. Insights into the role of miRNAs in host defense responses and host manipulation by microorganisms will enable a better understanding of host-microorganism interactions.

  11. Yeast genome-wide screen reveals dissimilar sets of host genes affecting replication of RNA viruses

    PubMed Central

    Panavas, Tadas; Serviene, Elena; Brasher, Jeremy; Nagy, Peter D.

    2005-01-01

    Viruses are devastating pathogens of humans, animals, and plants. To further our understanding of how viruses use the resources of infected cells, we systematically tested the yeast single-gene-knockout library for the effect of each host gene on the replication of tomato bushy stunt virus (TBSV), a positive-strand RNA virus of plants. The genome-wide screen identified 96 host genes whose absence either reduced or increased the accumulation of the TBSV replicon. The identified genes are involved in the metabolism of nucleic acids, lipids, proteins, and other compounds and in protein targeting/transport. Comparison with published genome-wide screens reveals that the replication of TBSV and brome mosaic virus (BMV), which belongs to a different supergroup among plus-strand RNA viruses, is affected by vastly different yeast genes. Moreover, a set of yeast genes involved in vacuolar targeting of proteins and vesicle-mediated transport both affected replication of the TBSV replicon and enhanced the cytotoxicity of the Parkinson's disease-related α-synuclein when this protein was expressed in yeast. In addition, a set of host genes involved in ubiquitin-dependent protein catabolism affected both TBSV replication and the cytotoxicity of a mutant huntingtin protein, a candidate agent in Huntington's disease. This finding suggests that virus infection and disease-causing proteins might use or alter similar host pathways and may suggest connections between chronic diseases and prior virus infection. PMID:15883361

  12. Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies

    PubMed Central

    Hassan, Mohamed; Selimovic, Denis; El-Khattouti, Abdelouahid; Ghozlan, Hanan; Haikel, Youssef; Abdelkader, Ola

    2012-01-01

    Hepatitis C virus (HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon based therapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection (HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies. PMID:24520529

  13. Host-parasite interactions and the evolution of ploidy.

    PubMed

    Nuismer, Scott L; Otto, Sarah P

    2004-07-27

    Although the majority of animals and plants, including humans, are dominated by the diploid phase of their life cycle, extensive diversity in ploidy level exists among eukaryotes, with some groups being primarily haploid whereas others alternate between haploid and diploid phases. Previous theory has illuminated conditions that favor the evolution of increased or decreased ploidy but has shed little light on which species should be primarily haploid and which primarily diploid. Here, we report a discovery that emerged from host-parasite models in which ploidy levels were allowed to evolve: selection is more likely to favor diploidy in host species and haploidy in parasite species. Essentially, when parasites must evade a host's immune system or defense response, selection favors parasitic individuals that express a narrow array of antigens and elicitors, thus favoring haploid parasites over diploid parasites. Conversely, when hosts must recognize a parasite before mounting a defensive response, selection favors hosts with a broader arsenal of recognition molecules, thus favoring diploid hosts over haploid hosts. These results are consistent with the predominance of haploidy among parasitic protists.

  14. Supramolecular Recognition Forces: An Examination of Weak Metal-Metal Interactions in Host-Guest Formation

    SciTech Connect

    Crowley, James D.; Steele, Ian M.; Bosnich, B.

    2008-10-03

    Molecular receptors consisting of two parallel-disposed terpy-M-Cl units (M = Pd{sup 2+}, Pt{sup 2+}) are used to form host-guest adducts with aromatic molecules and with neutral square-planar Pt{sup 2+} complexes. Host-guest formation is controlled by several factors including {pi}-{pi} interactions and, in some cases, weak Pt-Pt interactions between the host and the guest. This latter interaction was examined by comparing the host-guest stability of adducts formed by isoelectronic Pt{sup 2+} and Au{sup 3+} complexes with the Pt{sup 2+} receptor. Consistently, the former is more stable.

  15. Comparative genomics reveals adaptive evolution of Asian tapeworm in switching to a new intermediate host

    PubMed Central

    Wang, Shuai; Wang, Sen; Luo, Yingfeng; Xiao, Lihua; Luo, Xuenong; Gao, Shenghan; Dou, Yongxi; Zhang, Huangkai; Guo, Aijiang; Meng, Qingshu; Hou, Junling; Zhang, Bing; Zhang, Shaohua; Yang, Meng; Meng, Xuelian; Mei, Hailiang; Li, Hui; He, Zilong; Zhu, Xueliang; Tan, Xinyu; Zhu, Xing-quan; Yu, Jun; Cai, Jianping; Zhu, Guan; Hu, Songnian; Cai, Xuepeng

    2016-01-01

    Taenia saginata, Taenia solium and Taenia asiatica (beef, pork and Asian tapeworms, respectively) are parasitic flatworms of major public health and food safety importance. Among them, T. asiatica is a newly recognized species that split from T. saginata via an intermediate host switch ∼1.14 Myr ago. Here we report the 169- and 168-Mb draft genomes of T. saginata and T. asiatica. Comparative analysis reveals that high rates of gene duplications and functional diversifications might have partially driven the divergence between T. asiatica and T. saginata. We observe accelerated evolutionary rates, adaptive evolutions in homeostasis regulation, tegument maintenance and lipid uptakes, and differential/specialized gene family expansions in T. asiatica that may favour its hepatotropism in the new intermediate host. We also identify potential targets for developing diagnostic or intervention tools against human tapeworms. These data provide new insights into the evolution of Taenia parasites, particularly the recent speciation of T. asiatica. PMID:27653464

  16. Smart nanosystems: Bio-inspired technologies that interact with the host environment

    PubMed Central

    Kwon, Ester J.; Lo, Justin H.; Bhatia, Sangeeta N.

    2015-01-01

    Nanoparticle technologies intended for human administration must be designed to interact with, and ideally leverage, a living host environment. Here, we describe smart nanosystems classified in two categories: (i) those that sense the host environment and respond and (ii) those that first prime the host environment to interact with engineered nanoparticles. Smart nanosystems have the potential to produce personalized diagnostic and therapeutic schema by using the local environment to drive material behavior and ultimately improve human health. PMID:26598694

  17. The specificity of host-bat fly interaction networks across vegetation and seasonal variation.

    PubMed

    Zarazúa-Carbajal, Mariana; Saldaña-Vázquez, Romeo A; Sandoval-Ruiz, César A; Stoner, Kathryn E; Benitez-Malvido, Julieta

    2016-10-01

    Vegetation type and seasonality promote changes in the species composition and abundance of parasite hosts. However, it is poorly known how these variables affect host-parasite interaction networks. This information is important to understand the dynamics of parasite-host relationships according to biotic and abiotic changes. We compared the specialization of host-bat fly interaction networks, as well as bat fly and host species composition between upland dry forest and riparian forest and between dry and rainy seasons in a tropical dry forest in Jalisco, Mexico. Bat flies were surveyed by direct collection from bats. Our results showed that host-bat fly interaction networks were more specialized in upland dry forest compared to riparian forest. Bat fly species composition was different between the dry and rainy seasons, while host species composition was different between upland dry forest and riparian forest. The higher specialization in upland dry forest could be related to the differences in bat host species composition and their respective roosting habits. Variation in the composition of bat fly species between dry and rainy seasons coincides with the seasonal shifts in their species richness. Our study confirms the high specialization of host-bat fly interactions and shows the importance of biotic and abiotic factors to understand the dynamics of parasite-host interactions.

  18. Host protein Snapin interacts with human cytomegalovirus pUL130 and affects viral DNA replication.

    PubMed

    Wang, Guili; Ren, Gaowei; Cui, Xin; Lu, Zhitao; Ma, Yanpin; Qi, Ying; Huang, Yujing; Liu, Zhongyang; Sun, Zhengrong; Ruan, Qiang

    2016-06-01

    The interplay between the host and Human cytomegalovirus (HCMV) plays a pivotal role in the outcome of an infection. HCMV growth in endothelial and epithelial cells requires expression of viral proteins UL128, UL130, and UL131 proteins (UL128-131), of which UL130 is the largest gene and the only one that is not interrupted by introns.Mutation of the C terminus of the UL130 protein causes reduced tropism of endothelial cells (EC). However, very few host factors have been identified that interact with the UL130 protein. In this study, HCMV UL130 protein was shown to directly interact with the human protein Snapin in human embryonic kidney HEK293 cells by Yeast two-hybrid screening, in vitro glutathione S-transferase (GST) pull-down, and co-immunoprecipitation. Additionally, heterologous expression of protein UL130 revealed co-localization with Snapin in the cell membrane and cytoplasm of HEK293 cells using fluorescence confocal microscopy. Furthermore, decreasing the level of Snapin via specific small interfering RNAs decreased the number of viral DNA copies and titer inHCMV-infected U373-S cells. Taken together, these results suggest that Snapin, the pUL130 interacting protein, has a role in modulating HCMV DNA synthesis.

  19. Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins

    PubMed Central

    Ielasi, Francesco S.; Alioscha-Perez, Mitchel; Donohue, Dagmara; Claes, Sandra; Sahli, Hichem; Schols, Dominique

    2016-01-01

    ABSTRACT The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity. PMID:27406561

  20. Red Queen dynamics in multi-host and multi-parasite interaction system

    PubMed Central

    Rabajante, Jomar F.; Tubay, Jerrold M.; Uehara, Takashi; Morita, Satoru; Ebert, Dieter; Yoshimura, Jin

    2015-01-01

    In host-parasite systems, dominant host types are expected to be eventually replaced by other hosts due to the elevated potency of their specific parasites. This leads to changes in the abundance of both hosts and parasites exhibiting cycles of alternating dominance called Red Queen dynamics. Host-parasite models with less than three hosts and parasites have been demonstrated to exhibit Red Queen cycles, but natural host-parasite interactions typically involve many host and parasite types resulting in an intractable system with many parameters. Here we present numerical simulations of Red Queen dynamics with more than ten hosts and specialist parasites under the condition of no super-host nor super-parasite. The parameter region where the Red Queen cycles arise contracts as the number of interacting host and parasite types increases. The interplay between inter-host competition and parasite infectivity influences the condition for the Red Queen dynamics. Relatively large host carrying capacity and intermediate rates of parasite mortality result in never-ending cycles of dominant types. PMID:25899168

  1. Red Queen dynamics in multi-host and multi-parasite interaction system.

    PubMed

    Rabajante, Jomar F; Tubay, Jerrold M; Uehara, Takashi; Morita, Satoru; Ebert, Dieter; Yoshimura, Jin

    2015-04-22

    In host-parasite systems, dominant host types are expected to be eventually replaced by other hosts due to the elevated potency of their specific parasites. This leads to changes in the abundance of both hosts and parasites exhibiting cycles of alternating dominance called Red Queen dynamics. Host-parasite models with less than three hosts and parasites have been demonstrated to exhibit Red Queen cycles, but natural host-parasite interactions typically involve many host and parasite types resulting in an intractable system with many parameters. Here we present numerical simulations of Red Queen dynamics with more than ten hosts and specialist parasites under the condition of no super-host nor super-parasite. The parameter region where the Red Queen cycles arise contracts as the number of interacting host and parasite types increases. The interplay between inter-host competition and parasite infectivity influences the condition for the Red Queen dynamics. Relatively large host carrying capacity and intermediate rates of parasite mortality result in never-ending cycles of dominant types.

  2. Revealing physical interaction networks from statistics of collective dynamics.

    PubMed

    Nitzan, Mor; Casadiego, Jose; Timme, Marc

    2017-02-01

    Revealing physical interactions in complex systems from observed collective dynamics constitutes a fundamental inverse problem in science. Current reconstruction methods require access to a system's model or dynamical data at a level of detail often not available. We exploit changes in invariant measures, in particular distributions of sampled states of the system in response to driving signals, and use compressed sensing to reveal physical interaction networks. Dynamical observations following driving suffice to infer physical connectivity even if they are temporally disordered, are acquired at large sampling intervals, and stem from different experiments. Testing various nonlinear dynamic processes emerging on artificial and real network topologies indicates high reconstruction quality for existence as well as type of interactions. These results advance our ability to reveal physical interaction networks in complex synthetic and natural systems.

  3. Revealing physical interaction networks from statistics of collective dynamics

    PubMed Central

    Nitzan, Mor; Casadiego, Jose; Timme, Marc

    2017-01-01

    Revealing physical interactions in complex systems from observed collective dynamics constitutes a fundamental inverse problem in science. Current reconstruction methods require access to a system’s model or dynamical data at a level of detail often not available. We exploit changes in invariant measures, in particular distributions of sampled states of the system in response to driving signals, and use compressed sensing to reveal physical interaction networks. Dynamical observations following driving suffice to infer physical connectivity even if they are temporally disordered, are acquired at large sampling intervals, and stem from different experiments. Testing various nonlinear dynamic processes emerging on artificial and real network topologies indicates high reconstruction quality for existence as well as type of interactions. These results advance our ability to reveal physical interaction networks in complex synthetic and natural systems. PMID:28246630

  4. How does human-induced environmental change influence host-parasite interactions?

    PubMed

    Budria, Alexandre; Candolin, Ulrika

    2014-04-01

    Host-parasite interactions are an integral part of ecosystems that influence both ecological and evolutionary processes. Humans are currently altering environments the world over, often with drastic consequences for host-parasite interactions and the prevalence of parasites. The mechanisms behind the changes are, however, poorly known. Here, we explain how host-parasite interactions depend on two crucial steps--encounter rate and host-parasite compatibility--and how human activities are altering them and thereby host-parasite interactions. By drawing on examples from the literature, we show that changes in the two steps depend on the influence of human activities on a range of factors, such as the density and diversity of hosts and parasites, the search strategy of the parasite, and the avoidance strategy of the host. Thus, to unravel the mechanisms behind human-induced changes in host-parasite interactions, we have to consider the characteristics of all three parts of the interaction: the host, the parasite and the environment. More attention should now be directed to unfold these mechanisms, focusing on effects of environmental change on the factors that determine encounter rate and compatibility. We end with identifying several areas in urgent need of more investigations.

  5. Literature Mining and Ontology based Analysis of Host-Brucella Gene-Gene Interaction Network.

    PubMed

    Karadeniz, İlknur; Hur, Junguk; He, Yongqun; Özgür, Arzucan

    2015-01-01

    Brucella is an intracellular bacterium that causes chronic brucellosis in humans and various mammals. The identification of host-Brucella interaction is crucial to understand host immunity against Brucella infection and Brucella pathogenesis against host immune responses. Most of the information about the inter-species interactions between host and Brucella genes is only available in the text of the scientific publications. Many text-mining systems for extracting gene and protein interactions have been proposed. However, only a few of them have been designed by considering the peculiarities of host-pathogen interactions. In this paper, we used a text mining approach for extracting host-Brucella gene-gene interactions from the abstracts of articles in PubMed. The gene-gene interactions here represent the interactions between genes and/or gene products (e.g., proteins). The SciMiner tool, originally designed for detecting mammalian gene/protein names in text, was extended to identify host and Brucella gene/protein names in the abstracts. Next, sentence-level and abstract-level co-occurrence based approaches, as well as sentence-level machine learning based methods, originally designed for extracting intra-species gene interactions, were utilized to extract the interactions among the identified host and Brucella genes. The extracted interactions were manually evaluated. A total of 46 host-Brucella gene interactions were identified and represented as an interaction network. Twenty four of these interactions were identified from sentence-level processing. Twenty two additional interactions were identified when abstract-level processing was performed. The Interaction Network Ontology (INO) was used to represent the identified interaction types at a hierarchical ontology structure. Ontological modeling of specific gene-gene interactions demonstrates that host-pathogen gene-gene interactions occur at experimental conditions which can be ontologically represented. Our

  6. Bacterial receptors for host transferrin and lactoferrin: molecular mechanisms and role in host-microbe interactions.

    PubMed

    Morgenthau, Ari; Pogoutse, Anastassia; Adamiak, Paul; Moraes, Trevor F; Schryvers, Anthony B

    2013-12-01

    Iron homeostasis in the mammalian host limits the availability of iron to invading pathogens and is thought to restrict iron availability for microbes inhabiting mucosal surfaces. The presence of surface receptors for the host iron-binding glycoproteins transferrin (Tf) and lactoferrin (Lf) in globally important Gram-negative bacterial pathogens of humans and food production animals suggests that Tf and Lf are important sources of iron in the upper respiratory or genitourinary tracts, where they exclusively reside. Lf receptors have the additional function of protecting against host cationic antimicrobial peptides, suggesting that the bacteria expressing these receptors reside in a niche where exposure is likely. In this review we compare Tf and Lf receptors with respect to their structural and functional features, their role in colonization and infection, and their distribution among pathogenic and commensal bacteria.

  7. Immunoregulatory Effects Triggered by Lactic Acid Bacteria Exopolysaccharides: New Insights into Molecular Interactions with Host Cells.

    PubMed

    Laiño, Jonathan; Villena, Julio; Kanmani, Paulraj; Kitazawa, Haruki

    2016-08-15

    Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions. In addition, we describe our studies using porcine intestinal epithelial cells (PIE cells) as a model to evaluate the molecular interactions of EPS from two immunobiotic LAB strains and the host cells. Our studies showed that EPS from immunobiotic LAB have anti-inflammatory capacities in PIE cells since they are able to reduce the production of inflammatory cytokines in cells challenged with the Toll-like receptor (TLR)-4-agonist lipopolysaccharide. The effects of EPS were dependent on TLR2, TLR4, and negative regulators of TLR signaling. We also reported that the radioprotective 105 (RP105)/MD1 complex, a member of the TLR family, is partially involved in the immunoregulatory effects of the EPS from LAB. Our work described, for the first time, that LAB and their EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependent manner. A continuing challenge for the future is to reveal more effector-receptor relationships in immunobiotic-host interactions that contribute to the beneficial effects of these bacteria on mucosal immune homeostasis. A detailed molecular understanding should lead to a more rational use of immunobiotics in general, and their EPS in particular, as efficient prevention and therapies for specific immune-related disorders in humans and animals.

  8. Role of Retrograde Trafficking in Stress Response, Host Cell Interactions, and Virulence of Candida albicans

    PubMed Central

    Liu, Yaoping; Solis, Norma V.; Heilmann, Clemens J.; Phan, Quynh T.; Mitchell, Aaron P.; Klis, Frans M.

    2014-01-01

    In Saccharomyces cerevisiae, the vacuolar protein sorting complexes Vps51/52/53/54 and Vps15/30/34/38 are essential for efficient endosome-to-Golgi complex retrograde transport. Here we investigated the function of Vps15 and Vps51, representative members of these complexes, in the stress resistance, host cell interactions, and virulence of Candida albicans. We found that C. albicans vps15Δ/Δ and vps51Δ/Δ mutants had abnormal vacuolar morphology, impaired retrograde protein trafficking, and dramatically increased susceptibility to a variety of stressors. These mutants also had reduced capacity to invade and damage oral epithelial cells in vitro and attenuated virulence in the mouse model of oropharyngeal candidiasis. Proteomic analysis of the cell wall of the vps51Δ/Δ mutant revealed increased levels of the Crh11 and Utr2 transglycosylases, which are targets of the calcineurin signaling pathway. The transcript levels of the calcineurin pathway members CHR11, UTR2, CRZ1, CNA1, and CNA2 were elevated in the vps15Δ/Δ and vps51Δ/Δ mutants. Furthermore, these strains were highly sensitive to the calcineurin-specific inhibitor FK506. Also, deletion of CHR11 and UTR2 further increased the stress susceptibility of these mutants. In contrast, overexpression of CRH11 and UTR2 partially rescued their defects in stress resistance, but not host cell interactions. Therefore, intact retrograde trafficking in C. albicans is essential for stress resistance, host cell interactions, and virulence. Aberrant retrograde trafficking stimulates the calcineurin signaling pathway, leading to the increased expression of Chr11 and Utr2, which enables C. albicans to withstand environmental stress. PMID:24363364

  9. Immunoregulatory Effects Triggered by Lactic Acid Bacteria Exopolysaccharides: New Insights into Molecular Interactions with Host Cells

    PubMed Central

    Laiño, Jonathan; Villena, Julio; Kanmani, Paulraj; Kitazawa, Haruki

    2016-01-01

    Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions. In addition, we describe our studies using porcine intestinal epithelial cells (PIE cells) as a model to evaluate the molecular interactions of EPS from two immunobiotic LAB strains and the host cells. Our studies showed that EPS from immunobiotic LAB have anti-inflammatory capacities in PIE cells since they are able to reduce the production of inflammatory cytokines in cells challenged with the Toll-like receptor (TLR)-4-agonist lipopolysaccharide. The effects of EPS were dependent on TLR2, TLR4, and negative regulators of TLR signaling. We also reported that the radioprotective 105 (RP105)/MD1 complex, a member of the TLR family, is partially involved in the immunoregulatory effects of the EPS from LAB. Our work described, for the first time, that LAB and their EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependent manner. A continuing challenge for the future is to reveal more effector-receptor relationships in immunobiotic-host interactions that contribute to the beneficial effects of these bacteria on mucosal immune homeostasis. A detailed molecular understanding should lead to a more rational use of immunobiotics in general, and their EPS in particular, as efficient prevention and therapies for specific immune-related disorders in humans and animals. PMID:27681921

  10. Coevolutionary interactions between farmers and mafia induce host acceptance of avian brood parasites

    PubMed Central

    Hilbe, Christian; Traulsen, Arne

    2016-01-01

    Brood parasites exploit their host in order to increase their own fitness. Typically, this results in an arms race between parasite trickery and host defence. Thus, it is puzzling to observe hosts that accept parasitism without any resistance. The ‘mafia’ hypothesis suggests that these hosts accept parasitism to avoid retaliation. Retaliation has been shown to evolve when the hosts condition their response to mafia parasites, who use depredation as a targeted response to rejection. However, it is unclear if acceptance would also emerge when ‘farming’ parasites are present in the population. Farming parasites use depredation to synchronize the timing with the host, destroying mature clutches to force the host to re-nest. Herein, we develop an evolutionary model to analyse the interaction between depredatory parasites and their hosts. We show that coevolutionary cycles between farmers and mafia can still induce host acceptance of brood parasites. However, this equilibrium is unstable and in the long-run the dynamics of this host–parasite interaction exhibits strong oscillations: when farmers are the majority, accepters conditional to mafia (the host will reject first and only accept after retaliation by the parasite) have a higher fitness than unconditional accepters (the host always accepts parasitism). This leads to an increase in mafia parasites’ fitness and in turn induce an optimal environment for accepter hosts. PMID:27293783

  11. Transcriptomic Analysis Reveals Significant B Lymphocyte Suppression in Corticosteroid-Treated Hosts with Pneumocystis Pneumonia.

    PubMed

    Hu, Yang; Wang, Dong; Zhai, Kan; Tong, Zhaohui

    2017-03-01

    Pneumocystis pneumonia (PCP) is an opportunistic, infectious disease that is prevalent in immunosuppressed hosts. Corticosteroid treatment is the most significant risk factor for patients with PCP who are human immunodeficiency virus negative, although little is known about how corticosteroids alter the host defense against Pneumocystis infection. In the present study, we used transcriptome analysis to examine the immune response in the lungs of corticosteroid-treated PCP mice. The results showed down-regulation in the genes related to both native immunity, such as antigen processing and presentation, inflammatory response, and phagocytosis, as well as B and T lymphocyte immunity. The repression of gene expression, corresponding to B cell immunity, including B cell signaling, homeostasis, and Ig production, was prominent. The finding was confirmed by quantitative PCR of mouse lungs and the peripheral blood of patients with PCP. Flow cytometry also revealed a significant depletion of B cells in corticosteroid-treated PCP mice. Our study has highlighted that corticosteroid treatment suppresses the B cell immunity in the PCP host, which is likely one of the main reasons that corticosteroid treatment may stimulate PCP development.

  12. 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

  13. Spatial heterogeneity, frequency-dependent selection and polymorphism in host-parasite interactions

    PubMed Central

    2011-01-01

    Background Genomic and pathology analysis has revealed enormous diversity in genes involved in disease, including those encoding host resistance and parasite effectors (also known in plant pathology as avirulence genes). It has been proposed that such variation may persist when an organism exists in a spatially structured metapopulation, following the geographic mosaic of coevolution. Here, we study gene-for-gene relationships governing the outcome of plant-parasite interactions in a spatially structured system and, in particular, investigate the population genetic processes which maintain balanced polymorphism in both species. Results Following previous theory on the effect of heterogeneous environments on maintenance of polymorphism, we analysed a model with two demes in which the demes have different environments and are coupled by gene flow. Environmental variation is manifested by different coefficients of natural selection, the costs to the host of resistance and to the parasite of virulence, the cost to the host of being diseased and the cost to an avirulent parasite of unsuccessfully attacking a resistant host. We show that migration generates negative direct frequency-dependent selection, a condition for maintenance of stable polymorphism in each deme. Balanced polymorphism occurs preferentially if there is heterogeneity for costs of resistance and virulence alleles among populations and to a lesser extent if there is variation in the cost to the host of being diseased. We show that the four fitness costs control the natural frequency of oscillation of host resistance and parasite avirulence alleles. If demes have different costs, their frequencies of oscillation differ and when coupled by gene flow, there is amplitude death of the oscillations in each deme. Numerical simulations show that for a multiple deme island model, costs of resistance and virulence need not to be present in each deme for stable polymorphism to occur. Conclusions Our theoretical

  14. Individual Apostichopus japonicus fecal microbiome reveals a link with polyhydroxybutyrate producers in host growth gaps

    PubMed Central

    Yamazaki, Yohei; Meirelles, Pedro Milet; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Thompson, Fabiano L.; Sakai, Yuichi; Sawabe, Toko; Sawabe, Tomoo

    2016-01-01

    Gut microbiome shapes various aspects of a host’s physiology, but these functions in aquatic animal hosts have yet to be fully investigated. The sea cucumber Apostichopus japonicus Selenka is one such example. The large growth gap in their body size has delayed the development of intensive aquaculture, nevertheless the species is in urgent need of conservation. To understand possible contributions of the gut microbiome to its host’s growth, individual fecal microbiome comparisons were performed. High-throughput 16S rRNA sequencing revealed significantly different microbiota in larger and smaller individuals; Rhodobacterales in particular was the most significantly abundant bacterial group in the larger specimens. Further shotgun metagenome of representative samples revealed a significant abundance of microbiome retaining polyhydroxybutyrate (PHB) metabolism genes in the largest individual. The PHB metabolism reads were potentially derived from Rhodobacterales. These results imply a possible link between microbial PHB producers and potential growth promotion in Deuterostomia marine invertebrates. PMID:26905381

  15. Transplant Antennae and Host Brain Interact to Shape Odor Perceptual Space in Male Moths

    PubMed Central

    Lee, Seong-Gyu; Poole, Kathy; Linn, Charles E.; Vickers, Neil J.

    2016-01-01

    Behavioral responses to odors rely first upon their accurate detection by peripheral sensory organs followed by subsequent processing within the brain’s olfactory system and higher centers. These processes allow the animal to form a unified impression of the odor environment and recognize combinations of odorants as single entities. To investigate how interactions between peripheral and central olfactory pathways shape odor perception, we transplanted antennal imaginal discs between larval males of two species of moth Heliothis virescens and Heliothis subflexa that utilize distinct pheromone blends. During metamorphic development olfactory receptor neurons originating from transplanted discs formed connections with host brain neurons within olfactory glomeruli of the adult antennal lobe. The normal antennal receptor repertoire exhibited by males of each species reflects the differences in the pheromone blends that these species employ. Behavioral assays of adult transplant males revealed high response levels to two odor blends that were dissimilar from those that attract normal males of either species. Neurophysiological analyses of peripheral receptor neurons and central olfactory neurons revealed that these behavioral responses were a result of: 1. the specificity of H. virescens donor olfactory receptor neurons for odorants unique to the donor pheromone blend and, 2. central odor recognition by the H. subflexa host brain, which typically requires peripheral receptor input across 3 distinct odor channels in order to elicit behavioral responses. PMID:26816291

  16. Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1.

    PubMed

    Mehlitz, Adrian; Banhart, Sebastian; Mäurer, André P; Kaushansky, Alexis; Gordus, Andrew G; Zielecki, Julia; Macbeath, Gavin; Meyer, Thomas F

    2010-07-12

    Many bacterial pathogens translocate effector proteins into host cells to manipulate host cell functions. Here, we used a protein microarray comprising virtually all human SRC homology 2 (SH2) and phosphotyrosine binding domains to comprehensively and quantitatively assess interactions between host cell proteins and the early phase Chlamydia trachomatis effector protein translocated actin-recruiting phosphoprotein (Tarp), which is rapidly tyrosine phosphorylated upon host cell entry. We discovered numerous novel interactions between human SH2 domains and phosphopeptides derived from Tarp. The adaptor protein SHC1 was among Tarp's strongest interaction partners. Transcriptome analysis of SHC1-dependent gene regulation during infection indicated that SHC1 regulates apoptosis- and growth-related genes. SHC1 knockdown sensitized infected host cells to tumor necrosis factor-induced apoptosis. Collectively, our findings reveal a critical role for SHC1 in early C. trachomatis-induced cell survival and suggest that Tarp functions as a multivalent phosphorylation-dependent signaling hub that is important during the early phase of chlamydial infection.

  17. Phylogenetic exploration of hantaviruses in paraguay reveals reassortment and host switching in South America

    PubMed Central

    2011-01-01

    Background Longitudinal mark-recapture studies of rodents in two sites in the Mbaracayú Biosphere Reserve in the Interior Atlantic Forest of eastern Paraguay have revealed a complex and intriguing pattern of hantaviruses harbored by rodents in this area. Full-length sequencing and phylogenetic analyses were conducted for several rodents from Akodon montensis and Oligoryzomys fornesi. The phylogenetic relationships of these viruses were analyzed in the context of hantaviruses in South America with published S- and M-segment sequences. Findings Phylogenetic analyses of hantaviruses identified in the Mbaracayú Biosphere Reserve in Paraguay revealed Jabora and Juquitiba viruses are harbored by Akodon montensis and Oligoryzomys fornesi, respectively. These analyses revealed that in general the constituents of the major subclade for the S- and M-segments differ for the South American hantaviruses. Further, the two major groups within subclade C for the M-segment reflect in general the lethality associated with the viruses within each group. Conclusions Phylogenetic studies of Jabora and Juquitiba viruses and other Paraguayan viruses in the context of American hantaviruses revealed reassortment and host-switching in the evolution of South American hantaviruses. PMID:21838900

  18. Interactive host cells related to Mycoplasma suis α-enolase by yeast two-hybrid analysis.

    PubMed

    Liu, Mingming; Jia, Lijun; Li, Jixu; Xue, Shujiang; Gao, Xu; Yu, Longzheng; Zhang, Shoufa

    2014-10-01

    Mycoplasma suis belongs to the haemotrophic mycoplasmas, which colonise the red blood cells of a wide range of vertebrates. Adhesion to red blood cells is the crucial step in the unique lifecycle of M. suis. In addition to MSG1 protein, α-enolase is the second adhesion protein of M. suis, and may be involved in the adhesion of M. suis to porcine red blood cells (RBC). To simulate the environment of the RBC, we established the cDNA library of swine peripheral blood mononuclear cells (PBMC). The yeast two-hybrid (Y2H) system was adopted to screen α-enolase interactive proteins in the PBMC line. Alignment with the NCBI database revealed four interactive proteins: beta-actin, 60S ribosomal protein L11, clusterin precursor and endonuclease/reverse transcriptase. However, the M. suis α-enolase interactive proteins in the PBMC cDNA library obtained in the current study provide valuable information about the host cell interactions of the M. suis α-enolase protein.

  19. Mining Host-Pathogen Protein Interactions to Characterize Burkholderia mallei Infectivity Mechanisms

    DTIC Science & Technology

    2015-03-04

    RESEARCH ARTICLE Mining Host-Pathogen Protein Interactions to Characterize Burkholderia mallei Infectivity Mechanisms Vesna Memišević1, Nela...were shown to attenuate disease progression in an aerosol infection animal model using the virulent Burkholderia mallei ATCC 23344 strain. Here, we...host-cell environment for the successful establishment of host infections and intracellular spread. PLOS Computational Biology | DOI:10.1371

  20. Host pathogen interactions in Helicobacter pylori related gastric cancer.

    PubMed

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-03-07

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

  1. Host-Parasite Interactions and Population Dynamics of Rock Ptarmigan.

    PubMed

    Stenkewitz, Ute; Nielsen, Ólafur K; Skírnisson, Karl; Stefánsson, Gunnar

    2016-01-01

    Populations of rock ptarmigan (Lagopus muta) in Iceland fluctuate in multiannual cycles with peak numbers c. every 10 years. We studied the ptarmigan-parasite community and how parasites relate to ptarmigan age, body condition, and population density. We collected 632 ptarmigan in northeast Iceland in early October from 2006 to 2012; 630 (99.7%) were infected with at least one parasite species, 616 (98%) with ectoparasites, and 536 (85%) with endoparasites. We analysed indices for the combined parasite community (16 species) and known pathogenic parasites, two coccidian protozoans Eimeria muta and Eimeria rjupa, two nematodes Capillaria caudinflata and Trichostrongylus tenuis, one chewing louse Amyrsidea lagopi, and one skin mite Metamicrolichus islandicus. Juveniles overall had more ectoparasites than adults, but endoparasite levels were similar in both groups. Ptarmigan population density was associated with endoparasites, and in particular prevalence of the coccidian parasite Eimeria muta. Annual aggregation level of this eimerid fluctuated inversely with prevalence, with lows at prevalence peak and vice versa. Both prevalence and aggregation of E. muta tracked ptarmigan population density with a 1.5 year time lag. The time lag could be explained by the host specificity of this eimerid, host density dependent shedding of oocysts, and their persistence in the environment from one year to the next. Ptarmigan body condition was negatively associated with E. muta prevalence, an indication of their pathogenicity, and this eimerid was also positively associated with ptarmigan mortality and marginally inversely with fecundity. There were also significant associations between fecundity and chewing louse Amyrsidea lagopi prevalence (negative), excess juvenile mortality and nematode Capillaria caudinflata prevalence (positive), and adult mortality and skin mite Metamicrolichus islandicus prevalence (negative). Though this study is correlational, it provides strong

  2. Host-Parasite Interactions and Population Dynamics of Rock Ptarmigan

    PubMed Central

    Stenkewitz, Ute; Nielsen, Ólafur K.; Skírnisson, Karl; Stefánsson, Gunnar

    2016-01-01

    Populations of rock ptarmigan (Lagopus muta) in Iceland fluctuate in multiannual cycles with peak numbers c. every 10 years. We studied the ptarmigan-parasite community and how parasites relate to ptarmigan age, body condition, and population density. We collected 632 ptarmigan in northeast Iceland in early October from 2006 to 2012; 630 (99.7%) were infected with at least one parasite species, 616 (98%) with ectoparasites, and 536 (85%) with endoparasites. We analysed indices for the combined parasite community (16 species) and known pathogenic parasites, two coccidian protozoans Eimeria muta and Eimeria rjupa, two nematodes Capillaria caudinflata and Trichostrongylus tenuis, one chewing louse Amyrsidea lagopi, and one skin mite Metamicrolichus islandicus. Juveniles overall had more ectoparasites than adults, but endoparasite levels were similar in both groups. Ptarmigan population density was associated with endoparasites, and in particular prevalence of the coccidian parasite Eimeria muta. Annual aggregation level of this eimerid fluctuated inversely with prevalence, with lows at prevalence peak and vice versa. Both prevalence and aggregation of E. muta tracked ptarmigan population density with a 1.5 year time lag. The time lag could be explained by the host specificity of this eimerid, host density dependent shedding of oocysts, and their persistence in the environment from one year to the next. Ptarmigan body condition was negatively associated with E. muta prevalence, an indication of their pathogenicity, and this eimerid was also positively associated with ptarmigan mortality and marginally inversely with fecundity. There were also significant associations between fecundity and chewing louse Amyrsidea lagopi prevalence (negative), excess juvenile mortality and nematode Capillaria caudinflata prevalence (positive), and adult mortality and skin mite Metamicrolichus islandicus prevalence (negative). Though this study is correlational, it provides strong

  3. Host pathogen interactions in Helicobacter pylori related gastric cancer

    PubMed Central

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  4. Using metabarcoding to reveal and quantify plant-pollinator interactions

    PubMed Central

    Pornon, André; Escaravage, Nathalie; Burrus, Monique; Holota, Hélène; Khimoun, Aurélie; Mariette, Jérome; Pellizzari, Charlène; Iribar, Amaia; Etienne, Roselyne; Taberlet, Pierre; Vidal, Marie; Winterton, Peter; Zinger, Lucie; Andalo, Christophe

    2016-01-01

    Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole. PMID:27255732

  5. Using metabarcoding to reveal and quantify plant-pollinator interactions.

    PubMed

    Pornon, André; Escaravage, Nathalie; Burrus, Monique; Holota, Hélène; Khimoun, Aurélie; Mariette, Jérome; Pellizzari, Charlène; Iribar, Amaia; Etienne, Roselyne; Taberlet, Pierre; Vidal, Marie; Winterton, Peter; Zinger, Lucie; Andalo, Christophe

    2016-06-03

    Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole.

  6. Host-pathogen interactions in progressive chronic periodontitis.

    PubMed

    Hernández, M; Dutzan, N; García-Sesnich, J; Abusleme, L; Dezerega, A; Silva, N; González, F E; Vernal, R; Sorsa, T; Gamonal, J

    2011-10-01

    Periodontitis is an infection characterized by the occurrence of supporting tissue destruction with an episodic nature. Disease progression is often determined by the loss of attachment level or alveolar bone, and sequential probing of periodontal attachment remains the most commonly utilized method to diagnose progressive destruction of the periodontium. The tolerance method has been the most extensive clinical method used in recent years to determine site-specific attachment level changes. There is abundant evidence that major tissue destruction in periodontal lesions results from the recruitment of immune cells. Considerable effort has been made to study the host cell and mediator profiles involved in the pathogenesis of chronic periodontitis, but the definition of active sites, where current periodontal breakdown occurs, and consecutive characterization of the mediators involved are still among the main concerns. In the present review, we summarize periodontopathic bacteria and host factors, including infiltrating cell populations, cytokines, and host matrix metalloproteinases, associated with under-going episodic attachment loss that could partly explain the mechanisms involved in destruction of the supporting tissues of the tooth.

  7. HIV-1 p6-Another viral interaction partner to the host cellular protein cyclophilin A.

    PubMed

    Solbak, Sara M Ø; Reksten, Tove R; Röder, Rene; Wray, Victor; Horvli, Ole; Raae, Arnt J; Henklein, Petra; Henklein, Peter; Fossen, Torgils

    2012-04-01

    The 52-amino acid human immunodeficiency virus type 1 (HIV-1) p6 protein has previously been recognized as a docking site for several cellular and viral binding factors and is important for the formation of infectious viruses. A particular structural feature of p6 is the notably high relative content of proline residues, located at positions 5, 7, 10, 11, 24, 30, 37 and 49 in the sequence. Proline cis/trans isomerism was detected for all these proline residues to such an extent that more than 40% of all p6 molecules contain at least one proline in a cis conformation. 2D (1)H nuclear magnetic resonance analysis of full-length HIV-1 p6 and p6 peptides established that cyclophilin A (CypA) interacts as a peptidyl-prolyl cis/trans isomerase with all proline residues of p6. Only catalytic amounts of CypA were necessary for the interaction with p6 to occur, strongly suggesting that the observed interaction is highly relevant in vivo. In addition, surface plasmon resonance studies revealed binding of full-length p6 to CypA, and that this binding was significantly stronger than any of its N- or C-terminal peptides. This study demonstrates the first identification of an interaction between HIV-1 p6 and the host cellular protein CypA. The mode of interaction involves both transient enzyme-substrate interactions and a more stable binding. The binding motifs of p6 to Tsg-101, ALIX and Vpr coincide with binding regions and catalytic sites of p6 to CypA, suggesting a potential role of CypA in modulating functional interactions of HIV-1.

  8. Host responses to Plasmodium yoelii hepatic stages: a paradigm in host-parasite interaction.

    PubMed

    Lau, A O; Sacci, J B; Azad, A F

    2001-02-01

    The liver stage of malaria, caused by the genus Plasmodium, is clinically silent, but immunologically significant. Ample evidence exists for an effective CD8(+) T cell response to this stage as well as the involvement of gammadeltaT cells and NK1.1(int) cells in immunized animal models. In contrast, there is little information concerning responses in a naive host. Here we report that several host gene expressions in the liver, spleen, and kidney of BALB/c mice are altered during the liver stage of Plasmodium yoelii infection. Really interesting new gene 3 (Ring3), semaphorin subclass 4 member G, glutamylcysteine synthetase, and p45 NF erythroid 2 were all up-regulated 24 h after infection with P. yoelii. Semaphorin subclass 4 member G expression was elevated in the kidney, whereas Ring3 was elevated in both spleen and kidney. The expression of TNF-alpha (TNF-alpha and IFN-gamma) were down-regulated in all three tissues tested except in infected spleen where IFN-gamma was elevated. P. yoelii-related host gene changes were compared with those in Toxoplasma gondii-infected livers. Ring3 expression increased 5-fold over control values, whereas expression of the other transcripts remained unchanged. TNF-alpha and IFN-gamma expressions were increased in the Toxoplasma-infected livers. The uniform increase of Ring3 expression in both Plasmodium- and Toxoplasma-infected livers suggests an innate immune response against parasitic infections, whereas the other gene expression changes are consistent with Plasmodium parasite-specific responses. Taken together, these changes suggest the immune responses to P. yoelii infection are both parasite and organ specific.

  9. Dynamical Study of Guest-Host Orientational Interaction in LiquidCrystalline Materials

    SciTech Connect

    Truong, Thai Viet

    2005-01-01

    Guest-host interaction has long been a subject of interest in many disciplines. Emphasis is often on how a small amount of guest substance could significantly affect the properties of a host material. This thesis describe our work in studying a guest-host effect where dye-doping of liquid crystalline materials greatly enhances the optical Kerr nonlinearity of the material. The dye molecules, upon excitation and via intermolecular interaction, provides an extra torque to reorient the host molecules, leading to the enhanced optical Kerr nonlinearity. We carried out a comprehensive study on the dynamics of the photoexcited dye-doped liquid crystalline medium. Using various experimental techniques, we separately characterized the dynamical responses of the relevant molecular species present in the medium following photo-excitation, and thus were able to follow the transient process in which photo-excitation of the dye molecules exert through guest-host interaction a net torque on the host LC material, leading to the observed enhanced molecular reorientation. We also observed for the first time the enhanced reorientation in a pure liquid crystal system, where the guest population is created through photoexcitation of the host molecules themselves. Experimental results agree quantitatively with the time-dependent theory based on a mean-field model of the guest-host interaction.

  10. Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions

    DTIC Science & Technology

    2012-10-26

    viruses and vectors isolated over different geographic regions promote understanding of virus -vector co-evolution and the impact on dengue virus ...occurring dengue viruses . Vaccination may create an environment of relative low-transmission of natural dengue virus , within the human host and its... virus -host interactions resulting in increased dengue virus transmission and altered disease phenotype. Dengue viruses will be collected

  11. Supramolecular host-guest interaction for labeling and detection of cellular biomarkers.

    PubMed

    Agasti, Sarit S; Liong, Monty; Tassa, Carlos; Chung, Hyun Jung; Shaw, Stanley Y; Lee, Hakho; Weissleder, Ralph

    2012-01-09

    Be my guest: A supramolecular host-guest interaction is utilized for highly efficient bioorthogonal labeling of cellular targets. Antibodies labeled with a cyclodextrin host molecule bind to adamantane-labeled magnetofluorescent nanoparticles (see picture) and provide an amplifiable strategy for biomarker detection that can be adapted to different diagnostic techniques such as molecular profiling or magnetic cell sorting.

  12. Studying host cell protein interactions with monoclonal antibodies using high throughput protein A chromatography.

    PubMed

    Sisodiya, Vikram N; Lequieu, Joshua; Rodriguez, Maricel; McDonald, Paul; Lazzareschi, Kathlyn P

    2012-10-01

    Protein A chromatography is typically used as the initial capture step in the purification of monoclonal antibodies produced in Chinese hamster ovary (CHO) cells. Although exploiting an affinity interaction for purification, the level of host cell proteins in the protein A eluent varies significantly with different feedstocks. Using a batch binding chromatography method, we performed a controlled study to assess host cell protein clearance across both MabSelect Sure and Prosep vA resins. We individually spiked 21 purified antibodies into null cell culture fluid generated with a non-producing cell line, creating mock cell culture fluids for each antibody with an identical composition of host cell proteins and antibody concentration. We demonstrated that antibody-host cell protein interactions are primarily responsible for the variable levels of host cell proteins in the protein A eluent for both resins when antibody is present. Using the additives guanidine HCl and sodium chloride, we demonstrated that antibody-host cell protein interactions may be disrupted, reducing the level of host cell proteins present after purification on both resins. The reduction in the level of host cell proteins differed between antibodies suggesting that the interaction likely varies between individual antibodies but encompasses both an electrostatic and hydrophobic component.

  13. Literature Mining and Ontology based Analysis of Host-Brucella Gene–Gene Interaction Network

    PubMed Central

    Karadeniz, İlknur; Hur, Junguk; He, Yongqun; Özgür, Arzucan

    2015-01-01

    Brucella is an intracellular bacterium that causes chronic brucellosis in humans and various mammals. The identification of host-Brucella interaction is crucial to understand host immunity against Brucella infection and Brucella pathogenesis against host immune responses. Most of the information about the inter-species interactions between host and Brucella genes is only available in the text of the scientific publications. Many text-mining systems for extracting gene and protein interactions have been proposed. However, only a few of them have been designed by considering the peculiarities of host–pathogen interactions. In this paper, we used a text mining approach for extracting host-Brucella gene–gene interactions from the abstracts of articles in PubMed. The gene–gene interactions here represent the interactions between genes and/or gene products (e.g., proteins). The SciMiner tool, originally designed for detecting mammalian gene/protein names in text, was extended to identify host and Brucella gene/protein names in the abstracts. Next, sentence-level and abstract-level co-occurrence based approaches, as well as sentence-level machine learning based methods, originally designed for extracting intra-species gene interactions, were utilized to extract the interactions among the identified host and Brucella genes. The extracted interactions were manually evaluated. A total of 46 host-Brucella gene interactions were identified and represented as an interaction network. Twenty four of these interactions were identified from sentence-level processing. Twenty two additional interactions were identified when abstract-level processing was performed. The Interaction Network Ontology (INO) was used to represent the identified interaction types at a hierarchical ontology structure. Ontological modeling of specific gene–gene interactions demonstrates that host–pathogen gene–gene interactions occur at experimental conditions which can be ontologically

  14. Affinity proteomics reveals human host factors implicated in discrete stages of LINE-1 retrotransposition.

    PubMed

    Taylor, Martin S; LaCava, John; Mita, Paolo; Molloy, Kelly R; Huang, Cheng Ran Lisa; Li, Donghui; Adney, Emily M; Jiang, Hua; Burns, Kathleen H; Chait, Brian T; Rout, Michael P; Boeke, Jef D; Dai, Lixin

    2013-11-21

    LINE-1s are active human DNA parasites that are agents of genome dynamics in evolution and disease. These streamlined elements require host factors to complete their life cycles, whereas hosts have developed mechanisms to combat retrotransposition's mutagenic effects. As such, endogenous L1 expression levels are extremely low, creating a roadblock for detailed interactomic analyses. Here, we describe a system to express and purify highly active L1 RNP complexes from human suspension cell culture and characterize the copurified proteome, identifying 37 high-confidence candidate interactors. These data sets include known interactors PABPC1 and MOV10 and, with in-cell imaging studies, suggest existence of at least three types of compositionally and functionally distinct L1 RNPs. Among the findings, UPF1, a key nonsense-mediated decay factor, and PCNA, the polymerase-delta-associated sliding DNA clamp, were identified and validated. PCNA interacts with ORF2p via a PIP box motif; mechanistic studies suggest that this occurs during or immediately after target-primed reverse transcription.

  15. The civRT operon is important for Campylobacter jejuni strain 81-176 host cell interactions through regulation of the formate dehydrogenase operon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    C. jejuni colonizes the intestinal mucosa, and the severity of disease in different strains is correlated with host cell interaction and invasion. A microarray screen to identify genes differentially regulated during C. jejuni interaction with tissue culture cells revealed the up-regulation of a two...

  16. MicroRNAs as mediators of insect host-pathogen interactions and immunity.

    PubMed

    Hussain, Mazhar; Asgari, Sassan

    2014-11-01

    Insects are the most successful group of animals on earth, owing this partly to their very effective immune responses to microbial invasion. These responses mainly include cellular and humoral responses as well as RNA interference (RNAi). Small non-coding RNAs (snRNAs) produced through RNAi are important molecules in the regulation of gene expression in almost all living organisms; contributing to important processes such as development, differentiation, immunity as well as host-microorganism interactions. The main snRNAs produced by the RNAi response include short interfering RNAs, microRNAs and piwi-interacting RNAs. In addition to the host snRNAs, some microorganisms encode snRNAs that affect the dynamics of host-pathogen interactions. In this review, we will discuss the latest developments in regards to the role of microRNA in insect host-pathogen interactions and provide some insights into this rapidly developing area of research.

  17. Accounting for reciprocal host-microbiome interactions in experimental science.

    PubMed

    Stappenbeck, Thaddeus S; Virgin, Herbert W

    2016-06-09

    Mammals are defined by their metagenome, a combination of host and microbiome genes. This knowledge presents opportunities to further basic biology with translation to human diseases. However, the now-documented influence of the metagenome on experimental results and the reproducibility of in vivo mammalian models present new challenges. Here we provide the scientific basis for calling on all investigators, editors and funding agencies to embrace changes that will enhance reproducible and interpretable experiments by accounting for metagenomic effects. Implementation of new reporting and experimental design principles will improve experimental work, speed discovery and translation, and properly use substantial investments in biomedical research.

  18. Unraveling the secrets of Histoplasma capsulatum. A model to study morphogenic adaptation during parasite host/host interaction.

    PubMed

    Maresca, B

    1995-01-01

    Early in the developmental period of microbiology, Pasteur first observed the phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew as a filamentous mold aerobically on the surface of broth cultures but at the bottom of the flask where the environment was anaerobic it reproduced as budding yeast cells. Several infectious fungal pathogens of humans, namely Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenkii, and Coccidioides immitis change from a multicellular filamentous form to an unicellular morphology when they invade tissues. The ability of pathogenic fungi to assume a different shape is referred to as dimorphism. This phenomenon has intrigued clinicians, and medical mycologists since its discovery at the turn of the century. The ability of pathogens to initiate infection, invade host tissues and survive in mammalian hosts is critically linked to the induction of specific gene products. In dimorphic fungi, developmentally regulated gene expression is particularly important, since they may exist in phylogenetically distinct hosts with different body temperatures. Using Histoplasma capsulatum as a model to study parasite-host interactions at the biochemical and molecular level, my laboratory has attempted to relate the clinical spectrum of disease to natural variations in the characteristics of this organism and to adaptations it must make as a saprobe and a parasite. Histoplasma capsulatum is the etiologic agent of histoplasmosis, a respiratory infection that is world-wide in distribution. As a saprobe in soil it is mycelial, but it becomes a budding yeast as a parasite in susceptible hosts. These morphological phases can be reversibly reproduced in vitro by shifting the temperature from 25 degrees C, at which it is mycelial, to 37 degrees C, when it becomes a budding yeast. The process of mycelial-to-yeast conversion is of particular interest since it is triggered by an increase in

  19. Cold-active bacteriophages from the Baltic Sea ice have diverse genomes and virus-host interactions.

    PubMed

    Senčilo, Ana; Luhtanen, Anne-Mari; Saarijärvi, Mikko; Bamford, Dennis H; Roine, Elina

    2015-10-01

    Heterotrophic bacteria are the major prokaryotic component of the Baltic Sea ice microbiome, and it is postulated that phages are among their major parasites. In this study, we sequenced the complete genomes of six earlier reported phage isolates from the Baltic Sea ice infecting Shewanella sp. and Flavobacterium sp. hosts as well as characterized the phage-host interactions. Based on the genome sequences, the six phages were classified into five new genera. Only two phages, 1/4 and 1/40, both infecting Shewanella sp. strains, showed significant nucleotide sequence similarity to each other and could be grouped into the same genus. These two phages are also related to Vibrio-specific phages sharing approximately 25% of the predicted gene products. Nevertheless, cross-titrations showed that the cold-active phages studied are host specific: none of the seven additionally tested, closely related Shewanella strains served as hosts for the phages. Adsorption experiments of two Shewanella phages, 1/4 and 3/49, conducted at 4 °C and at 15 °C revealed relatively fast adsorption rates that are, for example, comparable with those of phages infective in mesophilic conditions. Despite the small number of Shewanella phages characterized here, we could already find different types of phage-host interactions including a putative abortive infection.

  20. Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions

    PubMed Central

    2017-01-01

    Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies. Nevertheless, the characterization of the proteins that function in the host-pathogen interface has been challenging, largely due to the technical challenges associated with detection of extracellular protein interactions. This review discusses available technologies for the high throughput study of extracellular protein interactions between pathogens and their hosts, with a focus on mammalian viruses and bacteria. Emerging work illustrates a rich landscape for extracellular host-pathogen interaction and points towards the evolution of multifunctional pathogen-encoded proteins. Further development and application of technologies for genome-wide identification of extracellular protein interactions will be important in deciphering functional host-pathogen interaction networks, laying the foundation for development of novel therapeutics. PMID:28321417

  1. The Protein Interaction Network of Bacteriophage Lambda with Its Host, Escherichia coli

    PubMed Central

    Blasche, Sonja; Wuchty, Stefan; Rajagopala, Seesandra V.

    2013-01-01

    Although most of the 73 open reading frames (ORFs) in bacteriophage λ have been investigated intensively, the function of many genes in host-phage interactions remains poorly understood. Using yeast two-hybrid screens of all lambda ORFs for interactions with its host Escherichia coli, we determined a raw data set of 631 host-phage interactions resulting in a set of 62 high-confidence interactions after multiple rounds of retesting. These links suggest novel regulatory interactions between the E. coli transcriptional network and lambda proteins. Targeted host proteins and genes required for lambda infection are enriched among highly connected proteins, suggesting that bacteriophages resemble interaction patterns of human viruses. Lambda tail proteins interact with both bacterial fimbrial proteins and E. coli proteins homologous to other phage proteins. Lambda appears to dramatically differ from other phages, such as T7, because of its unusually large number of modified and processed proteins, which reduces the number of host-virus interactions detectable by yeast two-hybrid screens. PMID:24049175

  2. Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry.

    PubMed

    Snyder, Greg A; Deredge, Daniel; Waldhuber, Anna; Fresquez, Theresa; Wilkins, David Z; Smith, Patrick T; Durr, Susi; Cirl, Christine; Jiang, Jiansheng; Jennings, William; Luchetti, Timothy; Snyder, Nathaniel; Sundberg, Eric J; Wintrode, Patrick; Miethke, Thomas; Xiao, T Sam

    2014-01-10

    The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules. Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR) signaling through molecular mimicry. The TIR domain-containing protein TcpB from Brucella inhibits TLR signaling through interaction with host adaptor proteins TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we have determined the X-ray crystal structures of the TIR domains from the Brucella protein TcpB and the host adaptor protein TIRAP. We have further characterized homotypic interactions of TcpB using hydrogen/deuterium exchange mass spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation and NF-κB reporter assays. The crystal structure of the TcpB TIR domain reveals the microtubule-binding site encompassing the BB loop as well as a symmetrical dimer mediated by the DD and EE loops. This dimerization interface is validated by peptide mapping through hydrogen/deuterium exchange mass spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N-terminal TIR domain fold containing a disulfide bond formed by Cys(89) and Cys(134). A comparison between the TcpB and TIRAP crystal structures reveals substantial conformational differences in the region that encompasses the BB loop. These findings underscore the similarities and differences in the molecular features found in the microbial and host TIR domains, which suggests mechanisms of bacterial mimicry of host signaling adaptor proteins, such as TIRAP.

  3. Host-microbe interactions in distal airways: relevance to chronic airway diseases.

    PubMed

    Martin, Clémence; Burgel, Pierre-Régis; Lepage, Patricia; Andréjak, Claire; de Blic, Jacques; Bourdin, Arnaud; Brouard, Jacques; Chanez, Pascal; Dalphin, Jean-Charles; Deslée, Gaetan; Deschildre, Antoine; Gosset, Philippe; Touqui, Lhousseine; Dusser, Daniel

    2015-03-01

    This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

  4. Macrophage-pathogen interactions in infectious diseases: new therapeutic insights from the zebrafish host model.

    PubMed

    Torraca, Vincenzo; Masud, Samrah; Spaink, Herman P; Meijer, Annemarie H

    2014-07-01

    Studying macrophage biology in the context of a whole living organism provides unique possibilities to understand the contribution of this extremely dynamic cell subset in the reaction to infections, and has revealed the relevance of cellular and molecular processes that are fundamental to the cell-mediated innate immune response. In particular, various recently established zebrafish infectious disease models are contributing substantially to our understanding of the mechanisms by which different pathogens interact with macrophages and evade host innate immunity. Transgenic zebrafish lines with fluorescently labeled macrophages and other leukocyte populations enable non-invasive imaging at the optically transparent early life stages. Furthermore, there is a continuously expanding availability of vital reporters for subcellular compartments and for probing activation of immune defense mechanisms. These are powerful tools to visualize the activity of phagocytic cells in real time and shed light on the intriguing paradoxical roles of these cells in both limiting infection and supporting the dissemination of intracellular pathogens. This Review will discuss how several bacterial and fungal infection models in zebrafish embryos have led to new insights into the dynamic molecular and cellular mechanisms at play when pathogens encounter host macrophages. We also describe how these insights are inspiring novel therapeutic strategies for infectious disease treatment.

  5. Experimental evidence of negative interspecific interactions among imago fleas: flea and host identities matter.

    PubMed

    Khokhlova, Irina S; Dlugosz, Elizabeth M; Krasnov, Boris R

    2016-03-01

    We investigated interspecific interactions between two flea species (Parapulex chephrenis and Xenopsylla ramesis) via evaluation of their feeding success (the size of a blood meal and time to death after a single blood meal) when they exploited rodent hosts [Acomys cahirinus (a characteristic host of the former) or Meriones crassus (a characteristic host of the latter)] in single-species or mixed-species groups. We predicted that the negative interactions between the two fleas will result in smaller blood meals and shorter survival time in mixed- versus single-species infestations. We also predicted that the negative effect of mixed-species infestation on feeding performance would be less pronounced when fleas exploited their characteristic host rather than a non-characteristic host. When exploiting a characteristic host, P. chephrenis took larger blood meals in single- than in mixed-species groups, whereas the blood meal size in X. ramesis did not differ between treatments. When exploiting a non-characteristic host, no effect of group composition was found in either flea species. Survival time after a single blood meal was not affected by co-infestation or host species in either flea. Our results suggest context-dependence of the negative effect of co-infestation on feeding performance in fleas with the manifestation of this effect varying in dependence of flea and host species identities.

  6. Interaction between visual and olfactory cues during host finding in the tomato fruit fly Neoceratitis cyanescens.

    PubMed

    Brévault, Thierry; Quilici, Serge

    2010-03-01

    Herbivorous insects searching for a host plant need to integrate a sequence of multimodal sensory inputs. We conducted a series of no-choice experiments in a laboratory wind tunnel to examine the behavioral response of the specialist fruit fly, Neoceratitis cyanescens (Diptera: Tephritidae), to host visual and olfactory stimuli presented singly or in combination (e.g., colored fruit model with or without host fruit odor). We also studied the influence of wind flow, age, and sex on the response of flies. In two-choice experiments, we evaluated the ability of mature females to discriminate between two fruit models emitting host vs. non-host fruit odor or clean air. Neoceratitis cyanescens mature females can use independently or interactively olfactory and visual stimuli to locate their host, whereas immature females and males respond primarily to host fruit odor. In the absence of wind, mature females mainly use visual information to locate the host fruit. In wind, host fruit odor significantly increases the probability and speed of locating the host fruit. In a two-choice situation between two bright orange spheres, flies accurately detected the sphere emitting host fruit odor vs. non-host fruit odor or odorless air. Nevertheless, they preferred to land on the bright orange sphere when the sphere emitting host fruit odor was blue. Furthermore, when odor source and fruit model were spatially decoupled (90 or 180 degrees ), >50% flies that landed on the fruit model initially performed an oriented flight toward the odor source, then turned back to the fruit model while in flight or after one landing, thus suggesting visual information to be the ultimate indicator of host fruit.

  7. Determining virus-host interactions and glycerol metabolism profiles in geographically diverse solar salterns with metagenomics

    PubMed Central

    Moller, Abraham G.

    2017-01-01

    Solar salterns are excellent model ecosystems for studying virus-microbial interactions because of their low microbial diversity, environmental stability, and high viral density. By using the power of CRISPR spacers to link viruses to their prokaryotic hosts, we explored virus-host interactions in geographically diverse salterns. Using taxonomic profiling, we identified hosts such as archaeal Haloquadratum, Halorubrum, and Haloarcula and bacterial Salinibacter, and we found that community composition related to not only salinity but also local environmental dynamics. Characterizing glycerol metabolism genes in these metagenomes suggested Halorubrum and Haloquadratum possess most dihydroxyacetone kinase genes while Salinibacter possesses most glycerol-3-phosphate dehydrogenase genes. Using two different methods, we detected fewer CRISPR spacers in Haloquadratum-dominated compared with Halobacteriaceae-dominated saltern metagenomes. After CRISPR detection, spacers were aligned against haloviral genomes to map virus to host. While most alignments for each saltern metagenome linked viruses to Haloquadratum walsbyi, there were also alignments indicating interactions with the low abundance taxa Haloarcula and Haloferax. Further examination of the dinucleotide and trinucleotide usage differences between paired viruses and their hosts confirmed viruses and hosts had similar nucleotide usage signatures. Detection of cas genes in the salterns supported the possibility of CRISPR activity. Taken together, our studies suggest similar virus-host interactions exist in different solar salterns and that the glycerol metabolism gene dihydroxyacetone kinase is associated with Haloquadratum and Halorubrum. PMID:28097058

  8. Interactive effects between diet and genotypes of host and pathogen define the severity of infection

    PubMed Central

    Zhang, Ji; Friman, Ville-Petri; Laakso, Jouni; Mappes, Johanna

    2012-01-01

    Host resistance and parasite virulence are influenced by multiple interacting factors in complex natural communities. Yet, these interactive effects are seldom studied concurrently, resulting in poor understanding of host-pathogen-environment dynamics. Here, we investigated how the level of opportunist pathogen virulence, strength of host immunity and the host condition manipulated via diet affect the survival of wood tiger moth Parasemia plantaginis (Arctidae). Larvae from “low cuticular melanin” and “high cuticular melanin” (considered as low and high pathogen resistance, respectively) selection lines were infected with moderately and highly virulent bacteria strains of Serratia marcescens, while simultaneously manipulating host diet (with or without antibacterial compounds). We measured host survival and food preference before and after infection to test whether the larvae “self-medicate” by choosing an anti-infection diet (Plantago major, i.e., plantain leaf) over lettuce (Lactuca sativa). “High melanin” larvae were more resistant than “low melanin” larvae to the less virulent strain that had slower growth and colonization rate compared with the more virulent strain. Cuticular melanin did not enhance survival when the larvae were infected with the highly virulent strain. Anti-infection diet enhanced survival of the “high melanin” but not the “low melanin” hosts. Survival was dependent on family origin even within the melanin selection lines. Despite the intrinsic preference for lettuce, no evidence of self-medication was found. These results demonstrate that the relative benefit of host cuticular melanin depends on both diet and pathogen virulence: plantain diet only boosted the immunity of already resistant “high melanin” hosts, and cuticular melanin increased host survival only when infected with moderately virulent pathogen. Moreover, there was considerable variation in host survival between families within both melanin lines

  9. Uncovering New Pathogen–Host Protein–Protein Interactions by Pairwise Structure Similarity

    PubMed Central

    Cui, Tao; Li, Weihui; Liu, Lei; Huang, Qiaoyun; He, Zheng-Guo

    2016-01-01

    Pathogens usually evade and manipulate host-immune pathways through pathogen–host protein–protein interactions (PPIs) to avoid being killed by the host immune system. Therefore, uncovering pathogen–host PPIs is critical for determining the mechanisms underlying pathogen infection and survival. In this study, we developed a computational method, which we named pairwise structure similarity (PSS)-PPI, to predict pathogen–host PPIs. First, a high-quality and non-redundant structure–structure interaction (SSI) template library was constructed by exhaustively exploring heteromeric protein complex structures in the PDB database. New interactions were then predicted by searching for PSS with complex structures in the SSI template library. A quantitative score named the PSS score, which integrated structure similarity and residue–residue contact-coverage information, was used to describe the overall similarity of each predicted interaction with the corresponding SSI template. Notably, PSS-PPI yielded experimentally confirmed pathogen–host PPIs of human immunodeficiency virus type 1 (HIV-1) with performance close to that of in vitro high-throughput screening approaches. Finally, a pathogen–host PPI network of human pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis, was constructed using PSS-PPI and refined using filtration steps based on cellular localization information. Analysis of the resulting network indicated that secreted proteins of the STPK, ESX-1, and PE/PPE family in M. tuberculosis targeted human proteins involved in immune response and phagocytosis. M. tuberculosis also targeted host factors known to regulate HIV replication. Taken together, our findings provide insights into the survival mechanisms of M. tuberculosis in human hosts, as well as co-infection of tuberculosis and HIV. With the rapid pace of three-dimensional protein structure discovery, the SSI template library we constructed and the PSS-PPI method we devised

  10. Dissecting host-virus interaction in lytic replication of a model herpesvirus.

    PubMed

    Dong, Xiaonan; Feng, Pinghui

    2011-10-07

    In response to viral infection, a host develops various defensive responses, such as activating innate immune signaling pathways that lead to antiviral cytokine production. In order to colonize the host, viruses are obligate to evade host antiviral responses and manipulate signaling pathways. Unraveling the host-virus interaction will shed light on the development of novel therapeutic strategies against viral infection. Murine γHV68 is closely related to human oncogenic Kaposi's sarcoma-associated herpesvirus and Epsten-Barr virus. γHV68 infection in laboratory mice provides a tractable small animal model to examine the entire course of host responses and viral infection in vivo, which are not available for human herpesviruses. In this protocol, we present a panel of methods for phenotypic characterization and molecular dissection of host signaling components in γHV68 lytic replication both in vivo and ex vivo. The availability of genetically modified mouse strains permits the interrogation of the roles of host signaling pathways during γHV68 acute infection in vivo. Additionally, mouse embryonic fibroblasts (MEFs) isolated from these deficient mouse strains can be used to further dissect roles of these molecules during γHV68 lytic replication ex vivo. Using virological and molecular biology assays, we can pinpoint the molecular mechanism of host-virus interactions and identify host and viral genes essential for viral lytic replication. Finally, a bacterial artificial chromosome (BAC) system facilitates the introduction of mutations into the viral factor(s) that specifically interrupt the host-virus interaction. Recombinant γHV68 carrying these mutations can be used to recapitulate the phenotypes of γHV68 lytic replication in MEFs deficient in key host signaling components. This protocol offers an excellent strategy to interrogate host-pathogen interaction at multiple levels of intervention in vivo and ex vivo. Recently, we have discovered that γHV68 usurps

  11. Predicting and Analyzing Interactions between Mycobacterium tuberculosis and Its Human Host

    PubMed Central

    Rapanoel, Holifidy A.; Mazandu, Gaston K.; Mulder, Nicola J.

    2013-01-01

    The outcome of infection by Mycobacterium tuberculosis (Mtb) depends greatly on how the host responds to the bacteria and how the bacteria manipulates the host, which is facilitated by protein–protein interactions. Thus, to understand this process, there is a need for elucidating protein interactions between human and Mtb, which may enable us to characterize specific molecular mechanisms allowing the bacteria to persist and survive under different environmental conditions. In this work, we used the interologs method based on experimentally verified intra-species and inter-species interactions to predict human-Mtb functional interactions. These interactions were further filtered using known human-Mtb interactions and genes that are differentially expressed during infection, producing 190 interactions. Further analysis of the subcellular location of proteins involved in these human-Mtb interactions confirms feasibility of these interactions. We also conducted functional analysis of human and Mtb proteins involved in these interactions, checking whether these proteins play a role in infection and/or disease, and enriching Mtb proteins in a previously predicted list of drug targets. We found that the biological processes of the human interacting proteins suggested their involvement in apoptosis and production of nitric oxide, whereas those of the Mtb interacting proteins were relevant to the intracellular environment of Mtb in the host. Mapping these proteins onto KEGG pathways highlighted proteins belonging to the tuberculosis pathway and also suggested that Mtb proteins might use the host to acquire nutrients, which is in agreement with the intracellular lifestyle of Mtb. This indicates that these interactions can shed light on the interplay between Mtb and its human host and thus, contribute to the process of designing novel drugs with new biological mechanisms of action. PMID:23844013

  12. Dynamics of the guest-host orientational interaction in dye-doped liquid-crystalline materials.

    PubMed

    Truong, Thai V; Xu, Lei; Shen, Y R

    2005-11-01

    We present a comprehensive study on the dynamics of laser-induced molecular reorientation in a dye-doped liquid crystalline (LC) medium that exhibits significant enhancement of the optical Kerr nonlinearity due to guest-host interaction. Using various techniques, we separately characterized the dynamical responses of the relevant molecular species present in the medium following photoexcitation and, thus, were able to follow the transient process in which photoexcitation of the dye molecules exert through guest-host interaction a net torque on the host LC material, leading to the observed enhanced optical Kerr nonlinearity. Experimental results agree quantitatively with the time-dependent theory based on a mean-field model of the guest-host interaction.

  13. Know your neighbor: Microbiota and host epithelial cells interact locally to control intestinal function and physiology.

    PubMed

    Sommer, Felix; Bäckhed, Fredrik

    2016-05-01

    Interactions between the host and its associated microbiota differ spatially and the local cross talk determines organ function and physiology. Animals and their organs are not uniform but contain several functional and cellular compartments and gradients. In the intestinal tract, different parts of the gut carry out different functions, tissue structure varies accordingly, epithelial cells are differentially distributed and gradients exist for several physicochemical parameters such as nutrients, pH, or oxygen. Consequently, the microbiota composition also differs along the length of the gut, but also between lumen and mucosa of the same intestinal segment, and even along the crypt-villus axis in the epithelium. Thus, host-microbiota interactions are highly site-specific and the local cross talk determines intestinal function and physiology. Here we review recent advances in our understanding of site-specific host-microbiota interactions and discuss their functional relevance for host physiology.

  14. Intestinal microbiome of poultry and its interaction with host and diet

    PubMed Central

    Pan, Deng; Yu, Zhongtang

    2014-01-01

    The gastrointestinal (GI) tract of poultry is densely populated with microorganisms which closely and intensively interact with the host and ingested feed. The gut microbiome benefits the host by providing nutrients from otherwise poorly utilized dietary substrates and modulating the development and function of the digestive and immune system. In return, the host provides a permissive habitat and nutrients for bacterial colonization and growth. Gut microbiome can be affected by diet, and different dietary interventions are used by poultry producers to enhance bird growth and reduce risk of enteric infection by pathogens. There also exist extensive interactions among members of the gut microbiome. A comprehensive understanding of these interactions will help develop new dietary or managerial interventions that can enhance bird growth, maximize host feed utilization, and protect birds from enteric diseases caused by pathogenic bacteria. PMID:24256702

  15. Structure Function Studies of Vaccinia Virus Host Range Protein K1 Reveal a Novel Functional Surface for Ankyrin Repeat Proteins

    SciTech Connect

    Li, Yongchao; Meng, Xiangzhi; Xiang, Yan; Deng, Junpeng

    2010-06-15

    Poxvirus host tropism at the cellular level is regulated by virus-encoded host range proteins acting downstream of virus entry. The functioning mechanisms of most host range proteins are unclear, but many contain multiple ankyrin (ANK) repeats, a motif that is known for ligand interaction through a concave surface. We report here the crystal structure of one of the ANK repeat-containing host range proteins, the vaccinia virus K1 protein. The structure, at a resolution of 2.3 {angstrom}, showed that K1 consists entirely of ANK repeats, including seven complete ones and two incomplete ones, one each at the N and C terminus. Interestingly, Phe82 and Ser83, which were previously shown to be critical for K1's function, are solvent exposed and located on a convex surface, opposite the consensus ANK interaction surface. The importance of this convex surface was further supported by our additional mutagenesis studies. We found that K1's host range function was negatively affected by substitution of either Asn51 or Cys47 and completely abolished by substitution of both residues. Cys47 and Asn51 are also exposed on the convex surface, spatially adjacent to Phe82 and Ser83. Altogether, our data showed that K1 residues on a continuous convex ANK repeat surface are critical for the host range function, suggesting that K1 functions through ligand interaction and does so with a novel ANK interaction surface.

  16. Nitric oxide production by necrotrophic pathogen Macrophomina phaseolina and the host plant in charcoal rot disease of jute: complexity of the interplay between necrotroph-host plant interactions.

    PubMed

    Sarkar, Tuhin Subhra; Biswas, Pranjal; Ghosh, Subrata Kumar; Ghosh, Sanjay

    2014-01-01

    M. phaseolina, a global devastating necrotrophic fungal pathogen causes charcoal rot disease in more than 500 host plants. With the aim of understanding the plant-necrotrophic pathogen interaction associated with charcoal rot disease of jute, biochemical approach was attempted to study cellular nitric oxide production under diseased condition. This is the first report on M. phaseolina infection in Corchorus capsularis (jute) plants which resulted in elevated nitric oxide, reactive nitrogen species and S nitrosothiols production in infected tissues. Time dependent nitric oxide production was also assessed with 4-Amino-5-Methylamino-2',7'-Difluorofluorescein Diacetate using single leaf experiment both in presence of M. phaseolina and xylanases obtained from fungal secretome. Cellular redox status and redox active enzymes were also assessed during plant fungal interaction. Interestingly, M. phaseolina was found to produce nitric oxide which was detected in vitro inside the mycelium and in the surrounding medium. Addition of mammalian nitric oxide synthase inhibitor could block the nitric oxide production in M. phaseolina. Bioinformatics analysis revealed nitric oxide synthase like sequence with conserved amino acid sequences in M. phaseolina genome sequence. In conclusion, the production of nitric oxide and reactive nitrogen species may have important physiological significance in necrotrophic host pathogen interaction.

  17. Molecular Dissection of Mycobacterium tuberculosis Integration Host Factor Reveals Novel Insights into the Mode of DNA Binding and Nucleoid Compaction*

    PubMed Central

    Sharadamma, Narayanaswamy; Harshavardhana, Yadumurthy; Ravishankar, Apoorva; Anand, Praveen; Chandra, Nagasuma; Muniyappa, K.

    2014-01-01

    The annotated whole-genome sequence of Mycobacterium tuberculosis revealed that Rv1388 (Mtihf) is likely to encode for a putative 20-kDa integration host factor (mIHF). However, very little is known about the functional properties of mIHF or the organization of the mycobacterial nucleoid. Molecular modeling of the mIHF three-dimensional structure, based on the cocrystal structure of Streptomyces coelicolor IHF duplex DNA, a bona fide relative of mIHF, revealed the presence of Arg-170, Arg-171, and Arg-173, which might be involved in DNA binding, and a conserved proline (Pro-150) in the tight turn. The phenotypic sensitivity of Escherichia coli ΔihfA and ΔihfB strains to UV and methyl methanesulfonate could be complemented with the wild-type Mtihf but not its alleles bearing mutations in the DNA-binding residues. Protein-DNA interaction assays revealed that wild-type mIHF, but not its DNA-binding variants, binds with high affinity to fragments containing attB and attP sites and curved DNA. Strikingly, the functionally important amino acid residues of mIHF and the mechanism(s) underlying its binding to DNA, DNA bending, and site-specific recombination are fundamentally different from that of E. coli IHFαβ. Furthermore, we reveal novel insights into IHF-mediated DNA compaction depending on the placement of its preferred binding sites; mIHF promotes DNA compaction into nucleoid-like or higher order filamentous structures. We therefore propose that mIHF is a distinct member of a subfamily of proteins that serve as essential cofactors in site-specific recombination and nucleoid organization and that these findings represent a significant advance in our understanding of the role(s) of nucleoid-associated proteins. PMID:25324543

  18. Adrenomedullin and mucosal defence: interaction between host and microorganism.

    PubMed

    Allaker, Robert P; Kapas, Supriya

    2003-04-15

    Many surface epithelial cells express adrenomedullin (AM) and it is postulated that it may have an important protective role. This peptide has many properties in common with other cationic antimicrobial peptides including the human beta-defensins. Antimicrobial activity against members of the human skin, oral, respiratory tract and gastric microflora has been demonstrated. Both pathogenic and commensal strains of bacteria are sensitive; Gram-positive and Gram-negative bacteria being equally susceptible. No activity against the yeast Candida albicans was observed. Minimum inhibitory and minimum bacteriocidal concentrations range from 7.75 x 10(-4) to 12.5 and 0.003 to >25.0 microg ml(-1), respectively. On exposure of oral, skin and gastric epithelial cells to whole cells and culture supernatants from bacteria isolated from these sites an increase in AM peptide and gene expression has been observed. No upregulation was detected with C. albicans. In cultured cells and an animal infection model increased AM peptide and gene expression has been demonstrated using immunohistochemical and in situ hybridization techniques. These collective findings suggest that AM represents a new category of antimicrobial peptide, which contributes to the mucosal host defence system.

  19. Avian metapneumovirus infection of chicken and turkey tracheal organ cultures: comparison of virus-host interactions.

    PubMed

    Hartmann, Sandra; Sid, Hicham; Rautenschlein, Silke

    2015-01-01

    Avian metapneumovirus (aMPV) is a pathogen with worldwide distribution, which can cause high economic losses in infected poultry. aMPV mainly causes infection of the upper respiratory tract in both chickens and turkeys, although turkeys seem to be more susceptible. Little is known about virus-host interactions at epithelial surfaces after aMPV infection. Tracheal organ cultures (TOC) are a suitable model to investigate virus-host interaction in the respiratory epithelium. Therefore, we investigated virus replication rates and lesion development in chicken and turkey TOC after infection with a virulent aMPV subtype A strain. Aspects of the innate immune response, such as interferon-α and inducible nitric oxide synthase mRNA expression, as well as virus-induced apoptosis were determined. The aMPV-replication rate was higher in turkey (TTOC) compared to chicken TOC (CTOC) (P < 0.05), providing circumstantial evidence that indeed turkeys may be more susceptible. The interferon-α response was down-regulated from 2 to 144 hours post infection in both species compared to virus-free controls (P < 0.05); this was more significant for CTOC than TTOC. Inducible nitric oxide synthase expression was significantly up-regulated in aMPV-A-infected TTOC and CTOC compared to virus-free controls (P < 0.05). However, the results suggest that NO may play a different role in aMPV pathogenesis between turkeys and chickens as indicated by differences in apoptosis rate and lesion development between species. Overall, our study reveals differences in innate immune response regulation and therefore may explain differences in aMPV - A replication rates between infected TTOC and CTOC, which subsequently lead to more severe clinical signs and a higher rate of secondary infections in turkeys.

  20. The Use of Arabidopsis to Study Interactions between Parasitic Angiosperms and Their Plant Hosts

    PubMed Central

    Goldwasser, Y.; Westwood, J. H.; Yoder, J. I.

    2002-01-01

    Parasitic plants invade host plants in order to rob them of water, minerals and nutrients. The consequences to the infected hosts can be debilitating and some of the world's most pernicious agricultural weeds are parasitic. Parasitic genera of the Scrophulariaceae and Orobanchaceae directly invade roots of neighboring plants via underground structures called haustoria. The mechanisms by which these parasites identify and associate with host plants present unsurpassed opportunities for studying chemical signaling in plant-plant interactions. Seeds of some parasites require specific host factors for efficient germination, thereby insuring the availability of an appropriate host root prior to germination. A second set of signal molecules is required to induce haustorium development and the beginning of heterotrophy. Later stages in parasitism also require the presence of host factors, although these have not yet been well characterized. Arabidopsis is being used as a model host plant to identify genetic loci associated with stimulating parasite germination, haustorium development, and parasite support. Arabidopsis is also being employed to explore how host plants respond to parasite attack. Current methodologies and recent findings in Arabidopsis – parasitic plant interactions will be discussed. PMID:22303205

  1. MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)

    SciTech Connect

    McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.; Hyduke, Daniel R.

    2011-12-01

    Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactions is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.

  2. Patterns of diversification of Afrotropical Otiteselline fig wasps: phylogenetic study reveals a double radiation across host figs and conservatism of host association.

    PubMed

    Jousselin, E; Van Noort, S; Rasplus, J-Y; Greeff, J M

    2006-01-01

    We studied the phylogenetic relationships of Otiteselline fig waSPS associated with Ficus in the Afrotropical region using rDNA sequences. African fig species usually host two species of Otiteselline fig waSPS. Phylogenetic analyses reveal that this pattern of association results from the radiation of two clades of waSPS superimposed on the fig system. Within each clade, wasp species generally cluster according to their host classification. The phylogenies of the two clades are also generally more congruent than expected by chance. Together these results suggest that Otiteselline wasp speciation is largely constrained by the diversification of their hosts. Finally, we show a difference in ovipositor length between the two Otiteselline species coexisting in the same Ficus species, which probably corresponds to ecological differences. The diversification of ecological niches within the fig is probably, with cospeciation, one of the key factors explaining the diversification and maintenance of species of parasites of the fig/pollinator system.

  3. An Ehrlichia chaffeensis tandem repeat protein interacts with multiple host targets involved in cell signaling, transcriptional regulation, and vesicle trafficking.

    PubMed

    Wakeel, Abdul; Kuriakose, Jeeba A; McBride, Jere W

    2009-05-01

    Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes forming cytoplasmic membrane-bound microcolonies called morulae. To survive and replicate within phagocytes, E. chaffeensis exploits the host cell by modulating a number of host cell processes, but the ehrlichial effector proteins involved are unknown. In this study, we determined that p47, a secreted, differentially expressed, tandem repeat (TR) protein, interacts with multiple host proteins associated with cell signaling, transcriptional regulation, and vesicle trafficking. Yeast two-hybrid analysis revealed that p47 interacts with polycomb group ring finger 5 (PCGF5) protein, Src protein tyrosine kinase FYN (FYN), protein tyrosine phosphatase non-receptor type 2 (PTPN2), and adenylate cyclase-associated protein 1 (CAP1). p47 interaction with these proteins was further confirmed by coimmunoprecipitation assays and colocalization in HeLa cells transfected with p47-green fluorescent fusion protein (AcGFP1-p47). Moreover, confocal microscopy demonstrated p47-expressing dense-cored (DC) ehrlichiae colocalized with PCGF5, FYN, PTPN2, and CAP1. An amino-terminally truncated form of p47 containing TRs interacted only with PCGF5 and not with FYN, PTPN2, and CAP1, indicating differences in p47 domains that are involved in these interactions. These results demonstrate that p47 is involved in a complex network of interactions involving numerous host cell proteins. Furthermore, this study provides a new insight into the molecular and functional distinction of DC ehrlichiae, as well as the effector proteins involved in facilitating ehrlichial survival in mononuclear phagocytes.

  4. Concurrent and subsequent tumors in the same host: a model to evaluate the host tumor interaction

    SciTech Connect

    Mendiondo, O.A.; Suit, H.D.; Phil, D.; Sedlacek, R.S.

    1980-02-01

    There is evidence which demonstrates an immune rejection response (IRR) directed against tumor cells in some experimental and human tumors. In the case of FSa-1, a methylchlolanthrene-induced fibrosarcoma of the C/sub 3/Hf/Sed mouse, the IRR is manifested by a decrease in the dose of radiation expected to control half of the treated tumors (TCD/sub 50/) and an increase in the number of tumor cells expected to transplant the tumor in half of the transplanted recipients (TD/sub 50/) in immunized hosts. FSaI was transplanted simultaneously in the right and left legs of male and female C/sub 3/Hf/Sed mice and each tumor was given 3750 rad when it measured 8 mm in diameter (viz the TCD/sub 50/ value for 8 mm FSaI growing as one isotransplant per animal). The two tumors in any one animal usually responded similarly with either permanent regression or local recurrence after irradiation. In a second experiment, a group of animals received also concurrent tumors. This time an immunogenic FSaI was transplanted in one side and a non immunogenic mammary carcinoma (MDAH-MCaIV) on the opposite side. The tumors were irradiated with TCD/sub 50/ doses (3750 rad for FSaI and 6500 for the less radioresponsive MCa). The distribution of local control and recurrence was probabilistic; 50% of the animals exhibited one tumor destroyed and one recurring. In a third experimental group mice were subsequently transplanted with FSaI. Mice who showed no recurrence after irradiation of their first FSaI showed a stronger tendency to reject the second implantation than those who previously had local recurrence and subsequent amputation. Retransplants were controlled more easily by irradiation in the group that had been successfully treated for the first transplant. These data indicate that within the inbred population of C/sub 3/Hf/Sed mice there is a relatively broad distribution of capacities to react effectively against the FSaI challenge.

  5. Testing GxG interactions between coinfecting microbial parasite genotypes within hosts

    PubMed Central

    Bose, Joy; Schulte, Rebecca D.

    2014-01-01

    Host–parasite interactions represent one of the strongest selection pressures in nature. They are often governed by genotype-specific (GxG) interactions resulting in host genotypes that differ in resistance and parasite genotypes that differ in virulence depending on the antagonist’s genotype. Another type of GxG interactions, which is often neglected but which certainly influences host–parasite interactions, are those between coinfecting parasite genotypes. Mechanistically, within-host parasite interactions may range from competition for limited host resources to cooperation for more efficient host exploitation. The exact type of interaction, i.e., whether competitive or cooperative, is known to affect life-history traits such as virulence. However, the latter has been shown for chosen genotype combinations only, not considering whether the specific genotype combination per se may influence the interaction (i.e., GxG interactions). Here, we want to test for the presence of GxG interactions between coinfections of the bacterium Bacillus thuringiensis infecting the nematode Caenorhabditis elegans by combining two non-pathogenic and five pathogenic strains in all possible ways. Furthermore, we evaluate whether the type of interaction, reflected by the direction of virulence change of multiple compared to single infections, is genotype-specific. Generally, we found no indication for GxG interactions between non-pathogenic and pathogenic bacterial strains, indicating that virulence of pathogenic strains is equally affected by both non-pathogenic strains. Specific genotype combinations, however, differ in the strength of virulence change, indicating that the interaction type between coinfecting parasite strains and thus the virulence mechanism is specific for different genotype combinations. Such interactions are expected to influence host–parasite interactions and to have strong implications for coevolution. PMID:24860594

  6. Interactions Within Susceptible Hosts Drive Establishment of Genetically Distinct Variants of an Insect-Borne Pathogen.

    PubMed

    Blaisdell, G K; Zhang, S; Bratburd, J R; Daane, K M; Cooper, M L; Almeida, R P P

    2015-08-01

    Coinfections are common, leading to pathogen interactions during transmission and establishment in a host. However, few studies have tested the relative strengths of pathogen interactions in vectors and hosts that determine the outcome of infection. We tested interactions between two genetically distinct variants of the mealybug-transmitted Grapevine leafroll-associated virus 3. The transmission efficiency of each variant in single variant inoculations by two vector species was determined. The effects of vector species, a coinfected source, and simultaneous inoculation from multiple hosts to one host on variant establishment were examined. Within-vector interactions could have a role in transmission from hosts containing mixed infections, but not when vectors were moved from separate singly infected source plants to a single recipient plant. The invasive Planococcus ficus (Signoret) was a more efficient vector than Pseudococcus viburni (Signoret). Transmission efficiency of the two variants did not differ in single variant inoculations. Overall infections were the same whether from singly or coinfected source plants. In mixed inoculations, establishment of one variant was reduced. Mixed inoculations from two singly infected source plants resulted in fewer mixed infections than expected by chance. Therefore, the observed outcome was determined subsequent to host inoculation rather than in the vector. The outcome may be due to resource competition between pathogens. Alternatively apparent competition may be responsible; the pathogens' differential ability to overcome host defenses and colonize the host may determine the final outcome of new infections. Detailed knowledge of interactions between pathogens during transmission and establishment could improve understanding and management of disease spread.

  7. Proteomics and integrative omic approaches for understanding host-pathogen interactions and infectious diseases.

    PubMed

    Jean Beltran, Pierre M; Federspiel, Joel D; Sheng, Xinlei; Cristea, Ileana M

    2017-03-27

    Organisms are constantly exposed to microbial pathogens in their environments. When a pathogen meets its host, a series of intricate intracellular interactions shape the outcome of the infection. The understanding of these host-pathogen interactions is crucial for the development of treatments and preventive measures against infectious diseases. Over the past decade, proteomic approaches have become prime contributors to the discovery and understanding of host-pathogen interactions that represent anti- and pro-pathogenic cellular responses. Here, we review these proteomic methods and their application to studying viral and bacterial intracellular pathogens. We examine approaches for defining spatial and temporal host-pathogen protein interactions upon infection of a host cell. Further expanding the understanding of proteome organization during an infection, we discuss methods that characterize the regulation of host and pathogen proteomes through alterations in protein abundance, localization, and post-translational modifications. Finally, we highlight bioinformatic tools available for analyzing such proteomic datasets, as well as novel strategies for integrating proteomics with other omic tools, such as genomics, transcriptomics, and metabolomics, to obtain a systems-level understanding of infectious diseases.

  8. Covariance in species diversity and facilitation among non-interactive parasite taxa: all against the host.

    PubMed

    Krasnov, B R; Mouillot, D; Khokhlova, I S; Shenbrot, G I; Poulin, R

    2005-10-01

    Different parasite taxa exploit different host resources and are often unlikely to interact directly. It is unclear, however, whether the diversity of any given parasite taxon is indirectly influenced by that of other parasite taxa on the same host. Some components of host immune defences may operate simultaneously against all kinds of parasites, whereas investment by the host in specific defences against one type of parasite may come at the expense of defence against other parasites. We investigated the relationships between the species diversity of 4 higher taxa of ectoparasites (fleas, sucking lice, mesostigmatid mites, and ixodid ticks), and between the species richness of ectoparasites and endoparasitic helminths, across different species of rodent hosts. Our analyses used 2 measures of species diversity, species richness and taxonomic distinctness, and controlled for the potentially confounding effects of sampling effort and phylogenetic relationships among host species. We found positive pairwise correlations between the species richness of fleas, mites and ticks; however, there was no association between species richness of any of these 3 groups and that of lice. We also found a strong positive relationship between the taxonomic distinctness of ecto- and endoparasite assemblages across host species. These results suggest the existence of a process of apparent facilitation among unrelated taxa in the organization of parasite communities. We propose explanations based on host immune responses, involving acquired cross-resistance to infection and interspecific variation in immunocompetence among hosts, to account for these patterns.

  9. Interactions between Trypanosoma cruzi Secreted Proteins and Host Cell Signaling Pathways

    PubMed Central

    Watanabe Costa, Renata; da Silveira, Jose F.; Bahia, Diana

    2016-01-01

    Chagas disease is one of the prevalent neglected tropical diseases, affecting at least 6–7 million individuals in Latin America. It is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to vertebrate hosts by blood-sucking insects. After infection, the parasite invades and multiplies in the myocardium, leading to acute myocarditis that kills around 5% of untreated individuals. T. cruzi secretes proteins that manipulate multiple host cell signaling pathways to promote host cell invasion. The primary secreted lysosomal peptidase in T. cruzi is cruzipain, which has been shown to modulate the host immune response. Cruzipain hinders macrophage activation during the early stages of infection by interrupting the NF-kB P65 mediated signaling pathway. This allows the parasite to survive and replicate, and may contribute to the spread of infection in acute Chagas disease. Another secreted protein P21, which is expressed in all of the developmental stages of T. cruzi, has been shown to modulate host phagocytosis signaling pathways. The parasite also secretes soluble factors that exert effects on host extracellular matrix, such as proteolytic degradation of collagens. Finally, secreted phospholipase A from T. cruzi contributes to lipid modifications on host cells and concomitantly activates the PKC signaling pathway. Here, we present a brief review of the interaction between secreted proteins from T. cruzi and the host cells, emphasizing the manipulation of host signaling pathways during invasion. PMID:27065960

  10. Within-host competitive interactions as a mechanism for the maintenance of parasite diversity

    PubMed Central

    Bashey, Farrah

    2015-01-01

    Variation among parasite strains can affect the progression of disease or the effectiveness of treatment. What maintains parasite diversity? Here I argue that competition among parasites within the host is a major cause of variation among parasites. The competitive environment within the host can vary depending on the parasite genotypes present. For example, parasite strategies that target specific competitors, such as bacteriocins, are dependent on the presence and susceptibility of those competitors for success. Accordingly, which parasite traits are favoured by within-host selection can vary from host to host. Given the fluctuating fitness landscape across hosts, genotype by genotype (G×G) interactions among parasites should be prevalent. Moreover, selection should vary in a frequency-dependent manner, as attacking genotypes select for resistance and genotypes producing public goods select for cheaters. I review competitive coexistence theory with regard to parasites and highlight a few key examples where within-host competition promotes diversity. Finally, I discuss how within-host competition affects host health and our ability to successfully treat infectious diseases. PMID:26150667

  11. Within-host competitive interactions as a mechanism for the maintenance of parasite diversity.

    PubMed

    Bashey, Farrah

    2015-08-19

    Variation among parasite strains can affect the progression of disease or the effectiveness of treatment. What maintains parasite diversity? Here I argue that competition among parasites within the host is a major cause of variation among parasites. The competitive environment within the host can vary depending on the parasite genotypes present. For example, parasite strategies that target specific competitors, such as bacteriocins, are dependent on the presence and susceptibility of those competitors for success. Accordingly, which parasite traits are favoured by within-host selection can vary from host to host. Given the fluctuating fitness landscape across hosts, genotype by genotype (G×G) interactions among parasites should be prevalent. Moreover, selection should vary in a frequency-dependent manner, as attacking genotypes select for resistance and genotypes producing public goods select for cheaters. I review competitive coexistence theory with regard to parasites and highlight a few key examples where within-host competition promotes diversity. Finally, I discuss how within-host competition affects host health and our ability to successfully treat infectious diseases.

  12. Roles of Complement C1q in Pneumococcus-Host Interactions.

    PubMed

    Agarwal, Vaibhav; Blom, Anna M

    2015-01-01

    The fight between a human host and a bacterial pathogen is highly complicated; each party tries to outshine the other in the race for survival. In humans, the innate immune system--in particular the complement system--functions as the first line of defence against invading pathogens. During the course of evolution, however, pathogens, in order to survive and perpetuate within a host, developed multiple strategies to counteract the host complement system and to colonize. One such pathogen is Streptococcus pneumoniae (pneumococcus), a gram-positive bacterial pathogen often commensal in the human respiratory tract. Depending on the host's susceptibility, pneumococci can transform into an infectious agent, disseminating within the human host and causing mild to life-threatening diseases. This transition from commensal to infectious agent is a highly complex process, and understanding of this mechanism is essential in controlling the pathogenicity of pneumococci. Using its intricate arsenal of weapons, such as surface-presenting adhesins as well as recruitment of host factor, pneumococci successfully colonize the host, a prerequisite for establishing infection. This review describes C1q, the first subunit of the classical complement pathway, and its role in pneumococcus-host interactions, whereby pneumococci exploit C1q as a molecular bridge facilitating host cellular adherence and invasion, a function not akin to the role of C1q in the defence mechanism.

  13. Antagonistic interaction networks are structured independently of latitude and host guild.

    PubMed

    Morris, Rebecca J; Gripenberg, Sofia; Lewis, Owen T; Roslin, Tomas

    2014-03-01

    An increase in species richness with decreasing latitude is a prominent pattern in nature. However, it remains unclear whether there are corresponding latitudinal gradients in the properties of ecological interaction networks. We investigated the structure of 216 quantitative antagonistic networks comprising insect hosts and their parasitoids, drawn from 28 studies from the High Arctic to the tropics. Key metrics of network structure were strongly affected by the size of the interaction matrix (i.e. the total number of interactions documented between individuals) and by the taxonomic diversity of the host taxa involved. After controlling for these sampling effects, quantitative networks showed no consistent structural patterns across latitude and host guilds, suggesting that there may be basic rules for how sets of antagonists interact with resource species. Furthermore, the strong association between network size and structure implies that many apparent spatial and temporal variations in network structure may prove to be artefacts.

  14. Anticipatory eye fixations reveal tool knowledge for tool interaction.

    PubMed

    Belardinelli, Anna; Barabas, Marissa; Himmelbach, Marc; Butz, Martin V

    2016-08-01

    Action-oriented eye-tracking studies have shown that eye fixations reveal much about current behavioral intentions. The eyes typically fixate those positions of a tool or an object where the fingers will be placed next, or those positions in a scene, where obstacles need to be avoided to successfully reach or transport a tool or object. Here, we asked to what extent eye fixations can also reveal active cognitive inference processes, which are expected to integrate bottom-up visual information with internal knowledge for planning suitable object interactions task-dependently. In accordance to the available literature, we expected that task-relevant knowledge will include sensorimotor, semantic, and mechanical aspects. To investigate if and in which way this internal knowledge influences eye fixation behavior while planning an object interaction, we presented pictures of familiar and unfamiliar tools and instructed participants to either pantomime 'lifting' or 'using' the respective tool. When confronted with unfamiliar tools, participants fixated the tool's effector part closer and longer in comparison with familiar tools. This difference was particularly prominent during 'using' trials when compared with 'lifting' trials. We suggest that this difference indicates that the brain actively extracts mechanical information about the unknown tool in order to infer its appropriate usage. Moreover, the successive fixations over a trial indicate that a dynamic, task-oriented, active cognitive process unfolds, which integrates available tool knowledge with visually gathered information to plan and determine the currently intended tool interaction.

  15. Tools for Single-Cell Kinetic Analysis of Virus-Host Interactions

    PubMed Central

    Swick, Adam; Yin, John

    2016-01-01

    Measures of cellular gene expression or behavior, when performed on individual cells, inevitably reveal a diversity of behaviors and outcomes that can correlate with normal or diseased states. For virus infections, the potential diversity of outcomes are pushed to an extreme, where measures of infection reflect features of the specific infecting virus particle, the individual host cell, as well as interactions between viral and cellular components. Single-cell measures, while revealing, still often rely on specialized fluid handling capabilities, employ end-point measures, and remain labor-intensive to perform. To address these limitations, we consider a new microwell-based device that uses simple pipette-based fluid handling to isolate individual cells. Our design allows different experimental conditions to be implemented in a single device, permitting easier and more standardized protocols. Further, we utilize a recently reported dual-color fluorescent reporter system that provides dynamic readouts of viral and cellular gene expression during single-cell infections by vesicular stomatitis virus. In addition, we develop and show how free, open-source software can enable streamlined data management and batch image analysis. Here we validate the integration of the device and software using the reporter system to demonstrate unique single-cell dynamic measures of cellular responses to viral infection. PMID:26752057

  16. The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

    PubMed Central

    Liu, Jared; Yan, Riceley; Zhong, Qiao; Ngo, Sam; Bangayan, Nathanael J; Nguyen, Lin; Lui, Timothy; Liu, Minghsun; Erfe, Marie C; Craft, Noah; Tomida, Shuta; Li, Huiying

    2015-01-01

    The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes phages isolated from acne patients and healthy individuals and by analyzing the P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes phage populations in the skin microbial community are often dominated by one strain. We also found phage strains shared among both related and unrelated individuals, suggesting that a pool of common phages exists in the human population and that transmission of phages may occur between individuals. To better understand the bacterium–phage interactions in the skin microbiota, we determined the outcomes of 74 genetically defined Propionibacterium strains challenged by 15 sequenced phages. Depending on the Propionibacterium lineage, phage infection can result in lysis, pseudolysogeny, or resistance. In type II P. acnes strains, we found that encoding matching clustered regularly interspaced short palindromic repeat spacers is insufficient to confer phage resistance. Overall, our findings suggest that the prey–predator relationship between bacteria and phages may have a role in modulating the composition of the microbiota. Our study also suggests that the microbiome structure of an individual may be an important factor in the design of phage-based therapy. PMID:25848871

  17. Histological and molecular studies of the non-host interaction between wheat and Uromyces fabae.

    PubMed

    Zhang, Hongchang; Wang, Chenfang; Cheng, Yulin; Wang, Xiaojie; Li, Feng; Han, Qingmei; Xu, Jinrong; Chen, Xianming; Huang, Lili; Wei, Guorong; Kang, Zhensheng

    2011-11-01

    Non-host resistance (NHR) confers plant species immunity against the majority of microbes. As an important crop, wheat can be damaged by several Puccinia species but is immune to all Uromyces species. Here, we studied the basis of NHR in wheat against the broad bean rust pathogen Uromyces fabae (Uf). In the wheat-Uf interaction, microscopic observations showed that urediospores germinated efficiently on wheat leaves. However, over 98% of the germ tubes failed to form appressoria over stomata. For the few that invaded through stomata, the majority of them failed to penetrate wheat mesophyll cells. At 96 hours after inoculation, less than 4% of the Uf infection units that had entered the mesophyll tissue formed haustoria. Attempted penetration by haustorium mother cells induced the thickening of cell wall and the formation of papillae in plant cells, which arrested the development or growth of Uf penetration pegs. For the Uf haustoria formed in wheat cells, they were encased in callose-like materials and did not elicit hypersensitive response. Localized accumulation of H(2)O(2) were observed in plant cell walls, papillae and encasement of haustoria during the wheat-Uf interaction. Furthermore, quantitative RT-PCR analysis showed that several genes involved in basal resistance and oxidative stress responses were up-regulated during Uf infection. In conclusion, our study revealed the cytological and molecular bases of NHR in wheat against the non-adapted rust fungus Uf, and highlighted the significance of papilla production in the prehaustorial NHR.

  18. The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin.

    PubMed

    Liu, Jared; Yan, Riceley; Zhong, Qiao; Ngo, Sam; Bangayan, Nathanael J; Nguyen, Lin; Lui, Timothy; Liu, Minghsun; Erfe, Marie C; Craft, Noah; Tomida, Shuta; Li, Huiying

    2015-09-01

    The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes phages isolated from acne patients and healthy individuals and by analyzing the P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes phage populations in the skin microbial community are often dominated by one strain. We also found phage strains shared among both related and unrelated individuals, suggesting that a pool of common phages exists in the human population and that transmission of phages may occur between individuals. To better understand the bacterium-phage interactions in the skin microbiota, we determined the outcomes of 74 genetically defined Propionibacterium strains challenged by 15 sequenced phages. Depending on the Propionibacterium lineage, phage infection can result in lysis, pseudolysogeny, or resistance. In type II P. acnes strains, we found that encoding matching clustered regularly interspaced short palindromic repeat spacers is insufficient to confer phage resistance. Overall, our findings suggest that the prey-predator relationship between bacteria and phages may have a role in modulating the composition of the microbiota. Our study also suggests that the microbiome structure of an individual may be an important factor in the design of phage-based therapy.

  19. Bactericidal Permeability-Increasing Proteins Shape Host-Microbe Interactions

    PubMed Central

    Chen, Fangmin; Krasity, Benjamin C.; Peyer, Suzanne M.; Koehler, Sabrina; Ruby, Edward G.

    2017-01-01

    ABSTRACT We characterized bactericidal permeability-increasing proteins (BPIs) of the squid Euprymna scolopes, EsBPI2 and EsBPI4. They have molecular characteristics typical of other animal BPIs, are closely related to one another, and nest phylogenetically among invertebrate BPIs. Purified EsBPIs had antimicrobial activity against the squid’s symbiont, Vibrio fischeri, which colonizes light organ crypt epithelia. Activity of both proteins was abrogated by heat treatment and coincubation with specific antibodies. Pretreatment under acidic conditions similar to those during symbiosis initiation rendered V. fischeri more resistant to the antimicrobial activity of the proteins. Immunocytochemistry localized EsBPIs to the symbiotic organ and other epithelial surfaces interacting with ambient seawater. The proteins differed in intracellular distribution. Further, whereas EsBPI4 was restricted to epithelia, EsBPI2 also occurred in blood and in a transient juvenile organ that mediates hatching. The data provide evidence that these BPIs play different defensive roles early in the life of E. scolopes, modulating interactions with the symbiont. PMID:28377525

  20. Host-Mycobacterium avium subsp. paratuberculosis interactome reveals a novel iron assimilation mechanism linked to nitric oxide stress during early infection

    PubMed Central

    2013-01-01

    Background The initial interaction between host cell and pathogen sets the stage for the ensuing infection and ultimately determine the course of disease. However, there is limited knowledge of the transcripts utilized by host and pathogen and how they may impact one another during this critical step. The purpose of this study was to create a host-Mycobacterium avium subsp. paratuberculosis (MAP) interactome for early infection in an epithelium-macrophage co-culture system using RNA-seq. Results Establishment of the host-MAP interactome revealed a novel iron assimilation system for carboxymycobactin. Iron assimilation is linked to nitric oxide synthase-2 production by the host and subsequent nitric oxide buildup. Iron limitation as well as nitric oxide is a prompt for MAP to enter into an iron sequestration program. This new iron sequestration program provides an explanation for mycobactin independence in some MAP strains grown in vitro as well as during infection within the host cell. Utilization of such a pathway is likely to aid MAP establishment and long-term survival within the host. Conclusions The host-MAP interactome identified a number of metabolic, DNA repair and virulence genes worthy for consideration as novel drug targets as well as future pathogenesis studies. Reported interactome data may also be utilized to conduct focused, hypothesis-driven research. Co-culture of uninfected bovine epithelial cells (MAC-T) and primary bovine macrophages creates a tolerant genotype as demonstrated by downregulation of inflammatory pathways. This co-culture system may serve as a model to investigate other bovine enteric pathogens. PMID:24112552

  1. Conditional Degradation of Plasmodium Calcineurin Reveals Functions in Parasite Colonization of both Host and Vector

    PubMed Central

    Philip, Nisha; Waters, Andrew P.

    2015-01-01

    Summary Functional analysis of essential genes in the malarial parasite, Plasmodium, is hindered by lack of efficient strategies for conditional protein regulation. We report the development of a rapid, specific, and inducible chemical-genetic tool in the rodent malaria parasite, P. berghei, in which endogenous proteins engineered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin. Application of AID to the calcium-regulated protein phosphatase, calcineurin, revealed functions in host and vector stages of parasite development. Whereas depletion of calcineurin in late-stage schizonts demonstrated its critical role in erythrocyte attachment and invasion in vivo, stage-specific depletion uncovered roles in gamete development, fertilization, and ookinete-to-oocyst and sporozoite-to-liver stage transitions. Furthermore, AID technology facilitated concurrent generation and phenotyping of transgenic lines, allowing multiple lines to be assessed simultaneously with significant reductions in animal use. This study highlights the broad applicability of AID for functional analysis of proteins across the Plasmodium life cycle. PMID:26118994

  2. Oligosaccharide binding proteins from Bifidobacterium longum subsp. infantis reveal a preference for host glycans.

    PubMed

    Garrido, Daniel; Kim, Jae Han; German, J Bruce; Raybould, Helen E; Mills, David A

    2011-03-15

    Bifidobacterium longum subsp. infantis (B. infantis) is a common member of the infant intestinal microbiota, and it has been characterized by its foraging capacity for human milk oligosaccharides (HMO). Its genome sequence revealed an overabundance of the Family 1 of solute binding proteins (F1SBPs), part of ABC transporters and associated with the import of oligosaccharides. In this study we have used the Mammalian Glycan Array to determine the specific affinities of these proteins. This was correlated with binding protein expression induced by different prebiotics including HMO. Half of the F1SBPs in B. infantis were determined to bind mammalian oligosaccharides. Their affinities included different blood group structures and mucin oligosaccharides. Related to HMO, other proteins were specific for oligomers of lacto-N-biose (LNB) and polylactosamines with different degrees of fucosylation. Growth on HMO induced the expression of specific binding proteins that import HMO isomers, but also bind blood group and mucin oligosaccharides, suggesting coregulated transport mechanisms. The prebiotic inulin induced other family 1 binding proteins with affinity for intestinal glycans. Most of the host glycan F1SBPs in B. infantis do not have homologs in other bifidobacteria. Finally, some of these proteins were found to be adherent to intestinal epithelial cells in vitro. In conclusion, this study represents further evidence for the particular adaptations of B. infantis to the infant gut environment, and helps to understand the molecular mechanisms involved in this process.

  3. Conditional Degradation of Plasmodium Calcineurin Reveals Functions in Parasite Colonization of both Host and Vector.

    PubMed

    Philip, Nisha; Waters, Andrew P

    2015-07-08

    Functional analysis of essential genes in the malarial parasite, Plasmodium, is hindered by lack of efficient strategies for conditional protein regulation. We report the development of a rapid, specific, and inducible chemical-genetic tool in the rodent malaria parasite, P. berghei, in which endogenous proteins engineered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin. Application of AID to the calcium-regulated protein phosphatase, calcineurin, revealed functions in host and vector stages of parasite development. Whereas depletion of calcineurin in late-stage schizonts demonstrated its critical role in erythrocyte attachment and invasion in vivo, stage-specific depletion uncovered roles in gamete development, fertilization, and ookinete-to-oocyst and sporozoite-to-liver stage transitions. Furthermore, AID technology facilitated concurrent generation and phenotyping of transgenic lines, allowing multiple lines to be assessed simultaneously with significant reductions in animal use. This study highlights the broad applicability of AID for functional analysis of proteins across the Plasmodium life cycle.

  4. The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

    PubMed Central

    Li, Jie; Chai, Qi-Yao; Liu, Cui Hua

    2016-01-01

    The ubiquitin system comprises enzymes that are responsible for ubiquitination and deubiquitination, as well as ubiquitin receptors that are capable of recognizing and deciphering the ubiquitin code, which act in coordination to regulate almost all host cellular processes, including host–pathogen interactions. In response to pathogen infection, the host innate immune system launches an array of distinct antimicrobial activities encompassing inflammatory signaling, phagosomal maturation, autophagy and apoptosis, all of which are fine-tuned by the ubiquitin system to eradicate the invading pathogens and to reduce concomitant host damage. By contrast, pathogens have evolved a cohort of exquisite strategies to evade host innate immunity by usurping the ubiquitin system for their own benefits. Here, we present recent advances regarding the ubiquitin system-mediated modulation of host–pathogen interplay, with a specific focus on host innate immune defenses and bacterial pathogen immune evasion. PMID:27524111

  5. Significance of Cuscutain, a cysteine protease from Cuscuta reflexa, in host-parasite interactions

    PubMed Central

    2010-01-01

    Background Plant infestation with parasitic weeds like Cuscuta reflexa induces morphological as well as biochemical changes in the host and the parasite. These modifications could be caused by a change in protein or gene activity. Using a comparative macroarray approach Cuscuta genes specifically upregulated at the host attachment site were identified. Results One of the infestation specific Cuscuta genes encodes a cysteine protease. The protein and its intrinsic inhibitory peptide were heterologously expressed, purified and biochemically characterized. The haustoria specific enzyme was named cuscutain in accordance with similar proteins from other plants, e.g. papaya. The role of cuscutain and its inhibitor during the host parasite interaction was studied by external application of an inhibitor suspension, which induced a significant reduction of successful infection events. Conclusions The study provides new information about molecular events during the parasitic plant - host interaction. Inhibition of cuscutain cysteine proteinase could provide means for antagonizing parasitic plants. PMID:20964874

  6. A Sensitive High-Throughput Assay for Evaluating Host-Pathogen Interactions in Cryptococcus neoformans Infection

    PubMed Central

    Srikanta, Deepa; Yang, Meng; Williams, Matthew; Doering, Tamara L.

    2011-01-01

    Background Cryptococcus neoformans causes serious disease in immunocompromised individuals, leading to over 600,000 deaths per year worldwide. Part of this impact is due to the organism's ability to thwart what should be the mammalian hosts' first line of defense against cryptococcal infection: internalization by macrophages. Even when C. neoformans is engulfed by host phagocytes, it can survive and replicate within them rather than being destroyed; this ability is central in cryptococcal virulence. It is therefore critical to elucidate the interactions of this facultative intracellular pathogen with phagocytic cells of its mammalian host. Methodology/Principal Findings To accurately assess initial interactions between human phagocytic cells and fungi, we have developed a method using high-throughput microscopy to efficiently distinguish adherent and engulfed cryptococci and quantitate each population. This method offers significant advantages over currently available means of assaying host-fungal cell interactions, and remains statistically robust when implemented in an automated fashion appropriate for screening. It was used to demonstrate the sensitivity of human phagocytes to subtle changes in the cryptococcal capsule, a major virulence factor of this pathogen. Conclusions/Significance Our high-throughput method for characterizing interactions between C. neoformans and mammalian phagocytic cells offers a powerful tool for elucidating the relationship between these cell types during pathogenesis. This approach will be useful for screens of this organism and has potentially broad applications for investigating host-pathogen interactions. PMID:21829509

  7. Insights From Natural Host-Parasite Interactions: The Drosophila Model

    PubMed Central

    Keebaugh, Erin S.; Schlenke, Todd A.

    2013-01-01

    Immune responses against opportunistic pathogens have been extensively studied in Drosophila, leading to a detailed map of the genetics behind innate immunity networks including the Toll, Imd, Jak-Stat, and JNK pathways. However, immune mechanisms of other organisms, particularly plants, have primarily been investigated using natural pathogens. It was the use of natural pathogens in plant research that revealed the plant R/Avr system, a specialized immune response derived from antagonistic coevolution between plant immune proteins and their natural pathogens’ virulence proteins. Thus, we recommend that researchers begin to use natural Drosophila pathogens to identify novel immune mechanisms that may have arisen through antagonistic coevolution with common natural pathogens. In this review, we address the benefits of using natural pathogens in research, describe the known natural pathogens of Drosophila, and discuss exciting prospects for future research on select natural pathogens of Drosophila. PMID:23764256

  8. Community interactions govern host-switching with implications for host–parasite coevolutionary history

    PubMed Central

    Harbison, Christopher W.; Clayton, Dale H.

    2011-01-01

    Reciprocal selective effects between coevolving species are often influenced by interactions with the broader ecological community. Community-level interactions may also influence macroevolutionary patterns of coevolution, such as cospeciation, but this hypothesis has received little attention. We studied two groups of ecologically similar feather lice (Phthiraptera: Ischnocera) that differ in their patterns of association with a single group of hosts. The two groups, “body lice” and “wing lice,” are both parasites of pigeons and doves (Columbiformes). Body lice are more host-specific and show greater population genetic structure than wing lice. The macroevolutionary history of body lice also parallels that of their columbiform hosts more closely than does the evolutionary history of wing lice. The closer association of body lice with hosts, compared with wing lice, can be explained if body lice are less capable of switching hosts than wing lice. Wing lice sometimes disperse phoretically on parasitic flies (Diptera: Hippoboscidae), but body lice seldom engage in this behavior. We tested the hypothesis that wing lice switch host species more often than body lice, and that the difference is governed by phoresis. Our results show that, where flies are present, wing lice switch to novel host species in sufficient numbers to establish viable populations on the new host. Body lice do not switch hosts, even where flies are present. Thus, differences in the coevolutionary history of wing and body lice can be explained by differences in host-switching, mediated by a member of the broader parasite community. PMID:21606369

  9. Cross-Species Virus-Host Protein-Protein Interactions Inhibiting Innate Immunity

    DTIC Science & Technology

    2016-07-01

    protein complex crystal structure. The black arrows indicate residue positions that are both present at the MDA5 – PIV5 V protein PPI interface and...16 Figure 15. Sequence comparison of host and putative host MDA5 sequences. MDA5 residues ( black bars) predicted to directly interact with V...polymerase subunit PB1 and human MAVS proteins. Virus Res., 172, 75-80 (2013). Scientific Presentations: L. Wayne Schultz, Joseph R. Luft, Eleanor Cook

  10. Insights into Adenovirus Uncoating from Interactions with Integrins and Mediators of Host Immunity

    PubMed Central

    Nemerow, Glen R.; Stewart, Phoebe L.

    2016-01-01

    Human adenoviruses are large (150 MDa) nonenveloped double-stranded DNA (dsDNA) viruses that cause acute respiratory, gastrointestinal and ocular infections. Despite these disease associations, adenovirus has aided basic and clinical research efforts through studies of its association with cells and as a target of host antiviral responses. This review highlights the knowledge of adenovirus disassembly and nuclear transport gleaned from structural, biophysical and functional analyses of adenovirus interactions with soluble and membrane-associated host molecules. PMID:28009821

  11. Dietary supply with polyunsaturated fatty acids and resulting maternal effects influence host – parasite interactions

    PubMed Central

    2013-01-01

    Background Interactions between hosts and parasites can be substantially modulated by host nutrition. Polyunsaturated fatty acids (PUFAs) are essential dietary nutrients; they are indispensable as structural components of cell membranes and as precursors for eicosanoids, signalling molecules which act on reproduction and immunity. Here, we explored the potential of dietary PUFAs to affect the course of parasitic infections using a well-established invertebrate host – parasite system, the freshwater herbivore Daphnia magna and its bacterial parasite Pasteuria ramosa. Results Using natural food sources differing in their PUFA composition and by experimentally modifying the availability of dietary arachidonic acid (ARA) and eicosapentaenoic acid (EPA) we examined PUFA-mediated effects resulting from direct consumption as well as maternal effects on offspring of treated mothers. We found that both host and parasite were affected by food quality. Feeding on C20 PUFA-containing food sources resulted in higher offspring production of hosts and these effects were conveyed to a great extent to the next generation. While feeding on a diet containing high PUFA concentrations significantly reduced the likelihood of becoming infected, the infection success in the next generation increased whenever the maternal diet contained PUFAs. We suggest that this opposing effect was caused by a trade-off between reproduction and immunity in the second generation. Conclusions Considering the direct and maternal effects of dietary PUFAs on host and parasite we propose that host – parasite interactions and thus disease dynamics under natural conditions are subject to the availability of dietary PUFAs. PMID:24175981

  12. A Photoresponsive Orthogonal Supramolecular Complex Based on Host-Guest Interactions.

    PubMed

    Wang, Dongsheng; Wagner, Manfred; Saydjari, Andrew K; Mueller, Julius; Winzen, Svenja; Butt, Hans-Jürgen; Wu, Si

    2017-02-21

    We synthesized a novel green-light-responsive tetra-ortho-isopropoxy-substituted azobenzene (ipAzo). Cis-ipAzo forms a strong host-guest complex with γ-cyclo dextrin (γ-CD) whereas trans-ipAzo binds weakly. This new photoresponsive host-guest interaction is reverse to the well-known azobenzene (Azo)/α-cyclodextrin (α-CD) complex, which is strong only between trans-Azo and α-CD. By combining the UV-light-responsive Azo/α-CD and green-light-responsive ipAzo/γ-CD host-guest complexes, a photoresponsive orthogonal supramolecular system is developed.

  13. Virus and host genomic, molecular, and cellular interactions during Marek's disease pathogenesis and oncogenesis

    PubMed Central

    McPherson, M. C.; Delany, M. E.

    2016-01-01

    Marek's Disease Virus (MDV) is a chicken alphaherpesvirus that causes paralysis, chronic wasting, blindness, and fatal lymphoma development in infected, susceptible host birds. This disease and its protective vaccines are highly relevant research targets, given their enormous impact within the poultry industry. Further, Marek's disease (MD) serves as a valuable model for the investigation of oncogenic viruses and herpesvirus patterns of viral latency and persistence—as pertinent to human health as to poultry health. The objectives of this article are to review MDV interactions with its host from a variety of genomic, molecular, and cellular perspectives. In particular, we focus on cytogenetic studies, which precisely assess the physical status of the MDV genome in the context of the chicken host genome. Combined, the cytogenetic and genomic research indicates that MDV-host genome interactions, specifically integration of the virus into the host telomeres, is a key feature of the virus life cycle, contributing to the viral achievement of latency, transformation, and reactivation of lytic replication. We present a model that outlines the variety of virus-host interactions, at the multiple levels, and with regard to the disease states. PMID:26755654

  14. The role of flagella and chemotaxis genes in host pathogen interaction of the host adapted Salmonella enterica serovar Dublin compared to the broad host range serovar S. Typhimurium

    PubMed Central

    2013-01-01

    Background The importance of flagella and chemotaxis genes in host pathogen interaction in Salmonella enterica is mainly based on studies of the broad host range serovar, S. Typhimurium, while little is known on the importance in host specific and host adapted serovars, such as S. Dublin. In the current study we have used previously characterized insertion mutants in flagella and chemotaxis genes to investigate this and possible differences in the importance between the two serovars. Results fliC (encoding the structural protein of the flagella) was essential for adhesion and fliC and cheB (CheB restores the chemotaxis system to pre-stimulus conformation) were essential for invasion of S. Dublin into epithelial Int407 cells. In S. Typhimurium, both lack of flagella (fliC/fljB double mutant) and cheB influenced adhesion, and invasion was influenced by lack of both cheA (the histidine-kinase of the chemotaxis system), fliC/fljB and cheB mutation. Uptake in J774A.1 macrophage cells was significantly reduced in cheA, cheB and fliC mutants of S. Dublin, while cheA was dispensable in S. Typhimurium. Removal of flagella in both serotypes caused an increased ability to propagate intracellular in J774 macrophage cells and decreased cytotoxicity toward these cells. Flagella and chemotaxis genes were found not to influence the oxidative response. The induction of IL-6 from J774A-1 cells depended on the presence of flagella in S. Typhimurium, whilst this was not the case following challenge with S. Dublin. Addition of fliC from S. Typhimurium in trans to a fliC mutant of S. Dublin increased cytotoxicity but it did not increase the IL-6 production. Flagella were demonstrated to contribute to the outcome of infection following oral challenge of mice in S. Dublin, while an S. Typhimurium fliC/fljB mutant showed increased virulence following intra peritoneal challenge. Conclusions The results showed that flagella and chemotaxis genes differed in their role in host pathogen

  15. Vpr-host interactions during HIV-1 viral life cycle.

    PubMed

    Zhao, Richard Y; Li, Ge; Bukrinsky, Michael I

    2011-06-01

    Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a multifunctional viral protein that plays important role at multiple stages of the HIV-1 viral life cycle. Although the molecular mechanisms underlying these activities are subject of ongoing investigations, overall, these activities have been linked to promotion of viral replication and impairment of anti-HIV immunity. Importantly, functional defects of Vpr have been correlated with slow disease progression of HIV-infected patients. Vpr is required for efficient viral replication in non-dividing cells such as macrophages, and it promotes, to some extent, viral replication in proliferating CD4+ T cells. The specific activities of Vpr include modulation of fidelity of viral reverse transcription, nuclear import of the HIV-1 pre-integration complex, transactivation of the HIV-1 LTR promoter, induction of cell cycle G2 arrest and cell death via apoptosis. In this review, we focus on description of the cellular proteins that specifically interact with Vpr and discuss their significance with regard to the known Vpr activities at each step of the viral life cycle in proliferating and non-proliferating cells.

  16. Host-parasite genetic interactions and virulence-transmission relationships in natural populations of monarch butterflies.

    PubMed

    de Roode, Jacobus C; Altizer, Sonia

    2010-02-01

    Evolutionary models predict that parasite virulence (parasite-induced host mortality) can evolve as a consequence of natural selection operating on between-host parasite transmission. Two major assumptions are that virulence and transmission are genetically related and that the relative virulence and transmission of parasite genotypes remain similar across host genotypes. We conducted a cross-infection experiment using monarch butterflies and their protozoan parasites from two populations in eastern and western North America. We tested each of 10 host family lines against each of 18 parasite genotypes and measured virulence (host life span) and parasite transmission potential (spore load). Consistent with virulence evolution theory, we found a positive relationship between virulence and transmission across parasite genotypes. However, the absolute values of virulence and transmission differed among host family lines, as did the rank order of parasite clones along the virulence-transmission relationship. Population-level analyses showed that parasites from western North America caused higher infection levels and virulence, but there was no evidence of local adaptation of parasites on sympatric hosts. Collectively, our results suggest that host genotypes can affect the strength and direction of selection on virulence in natural populations, and that predicting virulence evolution may require building genotype-specific interactions into simpler trade-off models.

  17. Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication.

    PubMed

    Cousins, Emily; Nicholas, John

    2014-01-01

    Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman's disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of "accessory" genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus-host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein-coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.

  18. Molecular Biology of Human Herpesvirus 8: Novel Functions and Virus–Host Interactions Implicated in Viral Pathogenesis and Replication

    PubMed Central

    Cousins, Emily; Nicholas, John

    2014-01-01

    Human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman’s disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of “accessory” genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus–host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein–coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus–host interactions and their potential roles in both virus biology and virus-associated disease. PMID:24008302

  19. Genetic background of host-pathogen interaction between Cucumis sativus L. and Pseudomonas syringae pv. lachrymans.

    PubMed

    Olczak-Woltman, H; Schollenberger, M; Niemirowicz-Szczytt, K

    2009-01-01

    The interplay of plant resistance mechanisms and bacterial pathogenicity is very complex. This applies also to the interaction that takes place between the pathogen Pseudomonas syringae pv. lachrymans (Smith et Bryan) and the cucumber (Cucumis sativus L.) as its host plant. Research on P. syringae pv. lachrymans has led to the discovery of specific factors produced during pathogenesis, i.e. toxins or enzymes. Similarly, studies on cucumber have identified the specific types of plant resistance expressed, namely Systemic Acquired Resistance (SAR) or Induced Systemic Resistance (ISR). This paper presents a summary of the current state of knowledge about this particular host-pathogen interaction, with reference to general information about interactions of P. syringae pathovars with host plants.

  20. CpG Dinucleotide Frequencies Reveal the Role of Host Methylation Capabilities in Parvovirus Evolution

    PubMed Central

    Upadhyay, Mohita; Samal, Jasmine; Kandpal, Manish; Vasaikar, Suhas; Biswas, Banhi; Gomes, James

    2013-01-01

    Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to “fractional” methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses. PMID:24109231

  1. CpG dinucleotide frequencies reveal the role of host methylation capabilities in parvovirus evolution.

    PubMed

    Upadhyay, Mohita; Samal, Jasmine; Kandpal, Manish; Vasaikar, Suhas; Biswas, Banhi; Gomes, James; Vivekanandan, Perumal

    2013-12-01

    Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to "fractional" methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.

  2. An experimental conflict of interest between parasites reveals the mechanism of host manipulation.

    PubMed

    Hafer, Nina; Milinski, Manfred

    2016-01-01

    Parasites can increase their host's predation susceptibility. It is a long-standing puzzle, whether this is caused by host manipulation, an evolved strategy of the parasite, or by side effects due to, for example, the parasite consuming energy from its host thereby changing the host's trade-off between avoiding predation and foraging toward foraging. Here, we use sequential infection of three-spined sticklebacks with the cestode Schistocephalus solidus so that parasites have a conflict of interest over the direction of host manipulation. With true manipulation, the not yet infective parasite should reduce rather than enhance risk taking because predation would be fatal for its fitness; if host behavior is changed by a side effect, the 2 parasites would add their increase of predation risk because both drain energy. Our results support the latter hypothesis. In an additional experiment, we tested both infected and uninfected fish either starved or satiated. True host manipulation should act independently of the fish's hunger status and continue when energy drain is balanced through satiation. Starvation and satiation affect the risk averseness of infected sticklebacks similarly to that of uninfected starved and satiated ones. Increased energy drain rather than active host manipulation dominates behavioral changes of S. solidus-infected sticklebacks.

  3. Experimental Models to Study the Role of Microbes in Host-Parasite Interactions

    PubMed Central

    Hahn, Megan A.; Dheilly, Nolwenn M.

    2016-01-01

    Until recently, parasitic infections have been primarily studied as interactions between the parasite and the host, leaving out crucial players: microbes. The recent realization that microbes play key roles in the biology of all living organisms is not only challenging our understanding of host-parasite evolution, but it also provides new clues to develop new therapies and remediation strategies. In this paper we provide a review of promising and advanced experimental organismal systems to examine the dynamic of host-parasite-microbe interactions. We address the benefits of developing new experimental models appropriate to this new research area and identify systems that offer the best promises considering the nature of the interactions among hosts, parasites, and microbes. Based on these systems, we identify key criteria for selecting experimental models to elucidate the fundamental principles of these complex webs of interactions. It appears that no model is ideal and that complementary studies should be performed on different systems in order to understand the driving roles of microbes in host and parasite evolution. PMID:27602023

  4. Co-infection with two strains of Brome mosaic bromovirus reveals common RNA recombination sites in different hosts.

    PubMed

    Kolondam, Beivy; Rao, Parth; Sztuba-Solinska, Joanna; Weber, Philipp H; Dzianott, Aleksandra; Johns, Mitrick A; Bujarski, Jozef J

    2015-01-01

    We have previously reported intra-segmental crossovers in Brome mosaic virus (BMV) RNAs. In this work, we studied the homologous recombination of BMV RNA in three different hosts: barley (Hordeum vulgare), Chenopodium quinoa, and Nicotiana benthamiana that were co-infected with two strains of BMV: Russian (R) and Fescue (F). Our work aimed at (1) establishing the frequency of recombination, (2) mapping the recombination hot spots, and (3) addressing host effects. The F and R nucleotide sequences differ from each other at many translationally silent nucleotide substitutions. We exploited this natural variability to track the crossover sites. Sequencing of a large number of cDNA clones revealed multiple homologous crossovers in each BMV RNA segment, in both the whole plants and protoplasts. Some recombination hot spots mapped at similar locations in different hosts, suggesting a role for viral factors, but other sites depended on the host. Our results demonstrate the chimeric ('mosaic') nature of the BMV RNA genome.

  5. Helminth fauna of chiropterans in Amazonia: biological interactions between parasite and host.

    PubMed

    de Albuquerque, Ana Cláudia Alexandre; Moraes, Marcela Figueiredo Duarte; Silva, Ana Carolina; Lapera, Ivan Moura; Tebaldi, José Hairton; Lux Hoppe, Estevam G

    2016-08-01

    Amazonia, the largest Brazilian biome, is one of the most diverse biomes around the world. Considering the Brazilian chiropteran species, 120 out of known 167 species are registered in Pará state, with 10 endemic species. Despite the high diversity of bats in Amazonia, studies on their parasites, especially on helminths, are scarce. Therefore, the present study aims to study the helminth fauna of different bats from the Pará state, Amazon biome, determine the descriptors of infection, and evaluate the host-parasite interactions, as well as evaluate differences in ecological indexes in accordance with the feeding guilds. The study was developed on 67 bats of 21 species captured in several areas of the Pará state. The animals were identified, divided into feeding guilds, and necropsied. The parasites obtained were identified and quantified. A total of 182 parasites were found in 20.89 % of the studied bats, representing nine species, as follows: Anenterotrema eduardocaballeroi, Anenterotrema liliputianum, Ochoterenatrema caballeroi, Tricholeiperia sp., Parahistiostrongylus octacanthus, Litomosoides guiterasi, Litomosoides brasiliensis, Capillariinae gen. sp., and Hymenolepididae gen. sp. Also, the results indicated that there was no impact of parasitism on host body condition and no relationship between sex and parasite intensity. In relation to the feeding guilds, the omnivores showed higher prevalence and mean intensity. Animals from regions closer to the equator tend to have greater richness in parasite species, but the present study revealed low diversity and richness in species. In conclusion, the ecological pattern observed for other animal groups, in which higher parasitic diversity are registered in lower latitudes, is not applicable to chiropterans from the study area.

  6. Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells.

    PubMed

    Wunsch, Christopher M; Lewis, Janina P

    2015-12-17

    Anaerobic bacteria far outnumber aerobes in many human niches such as the gut, mouth, and vagina. Furthermore, anaerobic infections are common and frequently of indigenous origin. The ability of some anaerobic pathogens to invade human cells gives them adaptive measures to escape innate immunity as well as to modulate host cell behavior. However, ensuring that the anaerobic bacteria are live during experimental investigation of the events may pose challenges. Porphyromonas gingivalis, a Gram-negative anaerobe, is capable of invading a variety of eukaryotic non-phagocytic cells. This article outlines how to successfully culture and assess the ability of P. gingivalis to invade human umbilical vein endothelial cells (HUVECs). Two protocols were developed: one to measure bacteria that can successfully invade and survive within the host, and the other to visualize bacteria interacting with host cells. These techniques necessitate the use of an anaerobic chamber to supply P. gingivalis with an anaerobic environment for optimal growth. The first protocol is based on the antibiotic protection assay, which is largely used to study the invasion of host cells by bacteria. However, the antibiotic protection assay is limited; only intracellular bacteria that are culturable following antibiotic treatment and host cell lysis are measured. To assess all bacteria interacting with host cells, both live and dead, we developed a protocol that uses fluorescent microscopy to examine host-pathogen interaction. Bacteria are fluorescently labeled with 2',7'-Bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and used to infect eukaryotic cells under anaerobic conditions. Following fixing with paraformaldehyde and permeabilization with 0.2% Triton X-100, host cells are labeled with TRITC phalloidin and DAPI to label the cell cytoskeleton and nucleus, respectively. Multiple images taken at different focal points (Z-stack) are obtained for temporal

  7. PHIDIAS: a pathogen-host interaction data integration and analysis system

    PubMed Central

    Xiang, Zuoshuang; Tian, Yuying; He, Yongqun

    2007-01-01

    The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated from peer-reviewed literature. PHIDIAS is publicly available at . PMID:17663773

  8. COI and ITS2 sequences delimit species, reveal cryptic taxa and host specificity of fig-associated Sycophila (Hymenoptera, Eurytomidae).

    PubMed

    Li, Yanwei; Zhou, Xin; Feng, Gui; Hu, Haoyuan; Niu, Liming; Hebert, Paul D N; Huang, Dawei

    2010-01-01

    Although the genus Sycophila has broad host preferences, some species are specifically associated with figs as nonpollinator wasps. Because of their sexual dimorphism, morphological plasticity, cryptic mating behaviour and poorly known biology, species identifications are often uncertain. It is particularly difficult to match conspecific females and males. In this study, we employed two molecular markers, mitochondrial COI and nuclear ITS2, to identify Sycophila from six Chinese fig species. Morphological studies revealed 25 female and male morphs, while sequence results for both genes were consistent in supporting the presence of 15 species, of which 13 were host specialists and two used dual hosts. A single species of Sycophila was respectively found on four fig species, but six species were isolated from Ficus benjamina and a same number was reared from Ficus microcarpa. Sequence results revealed three male morphs in one species and detected two species that were overlooked by morphological analysis.

  9. What do spring migrants reveal about sex and host selection in the melon aphid?

    PubMed Central

    2012-01-01

    Background Host plants exert considerable selective pressure on aphids because the plants constitute their feeding, mating and oviposition sites. Therefore, host specialisation in aphids evolves through selection of the behavioural and chemical mechanisms of host-plant location and recognition, and through metabolic adaptation to the phloem content of the host plant. How these adaptive traits evolve in an aphid species depends on the complexity of the annual life cycle of that species. The purpose of this field study was to determine how winged spring-migrant populations contribute to the evolution and maintenance of host specialisation in Aphis gossypii through host-plant choice and acceptance. We also assessed whether host-specialised genotypes corresponded exclusively to anholocyclic lineages regardless of the environmental conditions. Results The spring populations of cotton-melon aphids visiting newly planted melon crops exhibited an unexpectedly high level of genetic diversity that contrasted with the very low diversity characterising the host-specialised populations of this aphid species. This study illustrated in natura host-plant-selection pressure by showing the great differences in genetic diversity between the spring-migrant populations (alate aphids) and the melon-infesting populations (the apterous offspring of the alate aphids). Moreover, an analysis of the genetic composition of these alate and apterous populations in four geographic regions suggested differences in life-history strategies, such as host choice and reproductive mode, and questioned the common assertion that A. gossypii is an anholocyclic species throughout its distribution area, including Europe. Conclusions Our results clearly demonstrate that the melon plant acts as a selective filter against the reproduction of non-specialised individuals. We showed that olfactory cues are unlikely to be decisive in natura for host recognition by spring-migrant aphid populations that are not

  10. Mosquito-Host Interactions during and after an Outbreak of Equine Viral Encephalitis in Eastern Panama

    PubMed Central

    Navia-Gine, Wayra G.; Loaiza, Jose R.; Miller, Matthew J.

    2013-01-01

    Mosquito blood meals provide information about the feeding habits and host preference of potential arthropod-borne disease vectors. Although mosquito-borne diseases are ubiquitous in the Neotropics, few studies in this region have assessed patterns of mosquito-host interactions, especially during actual disease outbreaks. Based on collections made during and after an outbreak of equine viral encephalitis, we identified the source of 338 blood meals from 10 species of mosquitoes from Aruza Abajo, a location in Darien province in eastern Panama. A PCR based method targeting three distinct mitochondrial targets and subsequent DNA sequencing was used in an effort to delineate vector-host relationships. At Aruza Abajo, large domesticated mammals dominated the assemblage of mosquito blood meals while wild bird and mammal species represented only a small portion of the blood meal pool. Most mosquito species fed on a variety of hosts; foraging index analysis indicates that eight of nine mosquito species utilize hosts at similar proportions while a stochastic model suggests dietary overlap among species was greater than would be expected by chance. The results from our null-model analysis of mosquito diet overlap are consistent with the hypothesis that in landscapes where large domestic animals dominate the local biomass, many mosquito species show little host specificity, and feed upon hosts in proportion to their biomass, which may have implications for the role of livestocking patterns in vector-borne disease ecology. PMID:24339965

  11. The membrane as the gatekeeper of infection: Cholesterol in host-pathogen interaction.

    PubMed

    Kumar, G Aditya; Jafurulla, Md; Chattopadhyay, Amitabha

    2016-09-01

    The cellular plasma membrane serves as a portal for the entry of intracellular pathogens. An essential step for an intracellular pathogen to gain entry into a host cell therefore is to be able to cross the cell membrane. In this review, we highlight the role of host membrane cholesterol in regulating the entry of intracellular pathogens using insights obtained from work on the interaction of Leishmania and Mycobacterium with host cells. The entry of these pathogens is known to be dependent on host membrane cholesterol. Importantly, pathogen entry is inhibited either upon depletion (or complexation), or enrichment of membrane cholesterol. In other words, an optimum level of host membrane cholesterol is necessary for efficient infection by pathogens. In this overall context, we propose a general mechanism, based on cholesterol-induced conformational changes, involving cholesterol binding sites in host cell surface receptors that are implicated in this process. A therapeutic strategy targeting modulation of membrane cholesterol would have the advantage of avoiding the commonly encountered problem of drug resistance in tackling infection by intracellular pathogens. Insights into the role of host membrane cholesterol in pathogen entry would be instrumental in the development of novel therapeutic strategies to effectively tackle intracellular pathogenesis.

  12. Adaptation of mammalian host-pathogen interactions in a changing arctic environment

    PubMed Central

    2011-01-01

    Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic. PMID:21392401

  13. Interactions between the host innate immune system and microbes in inflammatory bowel disease.

    PubMed

    Abraham, Clara; Medzhitov, Ruslan

    2011-05-01

    The intestinal immune system defends against pathogens and entry of excessive intestinal microbes; simultaneously, a state of immune tolerance to resident intestinal microbes must be maintained. Perturbation of this balance is associated with intestinal inflammation in various mouse models and is thought to predispose humans to inflammatory bowel disease (IBD). The innate immune system senses microbes; dendritic cells, macrophages, and epithelial cells produce an initial, rapid response. The immune system continuously monitors resident microbiota and utilizes constitutive antimicrobial mechanisms to maintain immune homeostasis. associations between IBD and genes that regulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), genes that control autophagy (eg, ATG16L1, IRGM), and genes in the interleukin-23-T helper cell 17 pathway indicate the important roles of host-microbe interactions in regulating intestinal immune homeostasis. There is increasing evidence that intestinal microbes influence host immune development, immune responses, and susceptibility to human diseases such as IBD, diabetes mellitus, and obesity. Conversely, host factors can affect microbes, which in turn modulate disease susceptibility. We review the cell populations and mechanisms that mediate interactions between host defense and tolerance and how the dysregulation of host-microbe interactions leads to intestinal inflammation and IBD.

  14. Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior.

    PubMed

    Lyte, Mark

    2014-01-01

    The ability of microorganisms, whether present as commensals within the microbiota or introduced as part of a therapeutic regimen, to influence behavior has been demonstrated by numerous laboratories over the last few years. Our understanding of the mechanisms that are responsible for microbiota-gut-brain interactions is, however, lacking. The complexity of the microbiota is, of course, a contributing factor. Nonetheless, while microbiologists approaching the issue of microbiota-gut-brain interactions in the behavior well recognize such complexity, what is often overlooked is the equal complexity of the host neurophysiological system, especially within the gut which is differentially innervated by the enteric nervous system. As such, in the search for common mechanisms by which the microbiota may influence behavior one may look for mechanisms which are shared by both host and microbiota. Such interkingdom signaling can be found in the shared production of neurochemical mediators that are found in both eukaryotes and prokaryotes. The study of the production and recognition of neurochemicals that are exactly the same in structure to those produced in the vertebrate organisms is known as microbial endocrinology. The examination of the microbiota from the vantage point of host-microbiota neuroendocrine interactions cannot only identify new microbial endocrinology-based mechanisms by which the microbiota can influence host behavior, but also lead to the design of interventions in which the composition of the microbiota may be modulated in order to achieve a specific microbial endocrinology-based profile beneficial to overall host behavior.

  15. Highly Flexible, Tough, and Self-Healing Supramolecular Polymeric Materials Using Host-Guest Interaction.

    PubMed

    Nakahata, Masaki; Takashima, Yoshinori; Harada, Akira

    2015-09-23

    Flexible, tough, and self-healable polymeric materials are promising to be a solution to the energy problem by substituting for conventional heavy materials. A fusion of supramolecular chemistry and polymer chemistry is a powerful method to create such intelligent materials. Here, a supramolecular polymeric material using multipoint molecular recognition between cyclodextrin (CD) and hydrophobic guest molecules at polymer side chain is reported. A transparent, flexible, and tough hydrogel (host-guest gel) is formed by a simple preparation procedure. The host-guest gel shows self-healing property in both wet state and dry state due to reversible nature of host-guest interaction. The practical utility of the host-guest gel as a scratch curable coating is demonstrated.

  16. Interaction of Bacterial Exotoxins with Neutrophil Extracellular Traps: Impact for the Infected Host

    PubMed Central

    von Köckritz-Blickwede, Maren; Blodkamp, Stefanie; Nizet, Victor

    2016-01-01

    Since their discovery in 2004, neutrophil extracellular traps (NETs) have been characterized as a fundamental host innate immune defense against various pathogens. Released in response to infectious and pro-inflammatory stimuli, NETs can immobilize invading pathogens within a fibrous matrix consisting of DNA, histones, and antimicrobial peptides. Conversely, excessive or dysregulated NET release may hold a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during infectious challenge. In recent years, a number of microbial virulence factors have been shown to modulate formation of NETs, thereby facilitating colonization or spread within the host. In this mini-review we summarize the contemporary research on the interaction of bacterial exotoxins with neutrophils that modulate NET production, focusing particular attention on consequences for the host. Understanding host–pathogen dynamics in this extracellular battlefield of innate immunity may provide novel therapeutic approaches for infectious and inflammatory disorders. PMID:27064864

  17. Immunity against Helminths: Interactions with the Host and the Intercurrent Infections

    PubMed Central

    Moreau, Emmanuelle; Chauvin, Alain

    2010-01-01

    Helminth parasites are of considerable medical and economic importance. Studies of the immune response against helminths are of great interest in understanding interactions between the host immune system and parasites. Effector immune mechanisms against tissue-dwelling helminths and helminths localized in the lumen of organs, and their regulation, are reviewed. Helminth infections are characterized by an association of Th2-like and Treg responses. Worms are able to persist in the host and are mainly responsible for chronic infection despite a strong immune response developed by the parasitized host. Two types of protection against the parasite, namely, premune and partial immunities, have been described. Immune responses against helminths can also participate in pathogenesis. Th2/Treg-like immunomodulation allows the survival of both host and parasite by controlling immunopathologic disorders and parasite persistence. Consequences of the modified Th2-like responses on co-infection, vaccination, and inflammatory diseases are discussed. PMID:20150967

  18. Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium–host interactions

    PubMed Central

    Turroni, Francesca; Serafini, Fausta; Foroni, Elena; Duranti, Sabrina; O’Connell Motherway, Mary; Taverniti, Valentina; Mangifesta, Marta; Milani, Christian; Viappiani, Alice; Roversi, Tommaso; Sánchez, Borja; Santoni, Andrea; Gioiosa, Laura; Ferrarini, Alberto; Delledonne, Massimo; Margolles, Abelardo; Piazza, Laura; Palanza, Paola; Bolchi, Angelo; Guglielmetti, Simone; van Sinderen, Douwe; Ventura, Marco

    2013-01-01

    Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity. PMID:23776216

  19. Growth and host interaction of mouse segmented filamentous bacteria in vitro.

    PubMed

    Schnupf, Pamela; Gaboriau-Routhiau, Valérie; Gros, Marine; Friedman, Robin; Moya-Nilges, Maryse; Nigro, Giulia; Cerf-Bensussan, Nadine; Sansonetti, Philippe J

    2015-04-02

    The gut microbiota plays a crucial role in the maturation of the intestinal mucosal immune system of its host. Within the thousand bacterial species present in the intestine, the symbiont segmented filamentous bacterium (SFB) is unique in its ability to potently stimulate the post-natal maturation of the B- and T-cell compartments and induce a striking increase in the small-intestinal Th17 responses. Unlike other commensals, SFB intimately attaches to absorptive epithelial cells in the ileum and cells overlying Peyer's patches. This colonization does not result in pathology; rather, it protects the host from pathogens. Yet, little is known about the SFB-host interaction that underlies the important immunostimulatory properties of SFB, because SFB have resisted in vitro culturing for more than 50 years. Here we grow mouse SFB outside their host in an SFB-host cell co-culturing system. Single-celled SFB isolated from monocolonized mice undergo filamentation, segmentation, and differentiation to release viable infectious particles, the intracellular offspring, which can colonize mice to induce signature immune responses. In vitro, intracellular offspring can attach to mouse and human host cells and recruit actin. In addition, SFB can potently stimulate the upregulation of host innate defence genes, inflammatory cytokines, and chemokines. In vitro culturing thereby mimics the in vivo niche, provides new insights into SFB growth requirements and their immunostimulatory potential, and makes possible the investigation of the complex developmental stages of SFB and the detailed dissection of the unique SFB-host interaction at the cellular and molecular levels.

  20. Interaction of the ΦHSIC Virus with Its Host: Lysogeny or Pseudolysogeny?

    PubMed Central

    Williamson, S. J.; McLaughlin, M. R.; Paul, J. H.

    2001-01-01

    The marine phage ΦHSIC has been previously reported to enter into a lysogenic relationship with its host, HSIC, identified as Listonella pelagia. This phage produces a variety of plaques on its host, including turbid and haloed plaques, from which lysogens were previously isolated. These lysogens were unstable during long-term storage at −80° C and were lost. When HSIC was reinfected with phage ΦHSIC, pseudolysogen-like interactions between the phage and its host were observed. The cells (termed HSIC-2 or HSIC-2e) produced high viral titers (1011 ml−1) in the absence of inoculating phage and yet reached culture densities of nearly 109 ml−1. Prophages were not induced by mitomycin C or the polyaromatic hydrocarbon naphthalene in cells harboring such infections. However, such cells were homoimmune to superinfection. Colonies hybridized strongly with a gene probe from a 100-bp fragment of the ΦHSIC genome, while the host did not. Analysis of chromosomal DNA preparations suggested the presence of a chromosomally integrated prophage. Phage adsorption experiments suggested that HSIC-2 was adsorption impaired. Because of the chromosomal prophage integration and homoimmunity, we interpret these results to indicate that ΦHSIC establishes a lysogenic relationship with its host that involves an extremely high level of spontaneous induction. This could be caused by a weak repressor of phage production. Additionally, poor phage adsorption of HSIC-2 compared to the wild type probably helped maintain this pseudolysogen-like relationship. In many ways, pseudolysogenic phage-host interactions may provide a paradigm for phage-host interactions in the marine environment. PMID:11282621

  1. Multi-Omics Studies towards Novel Modulators of Influenza A Virus–Host Interaction

    PubMed Central

    Söderholm, Sandra; Fu, Yu; Gaelings, Lana; Belanov, Sergey; Yetukuri, Laxman; Berlinkov, Mikhail; Cheltsov, Anton V.; Anders, Simon; Aittokallio, Tero; Nyman, Tuula A.; Matikainen, Sampsa; Kainov, Denis E.

    2016-01-01

    Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV–host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV–host interactions, which might be more effective than the currently available anti-influenza therapeutics. PMID:27690086

  2. Host-Virus Interaction of ZIKA Virus in Modulating Disease Pathogenesis.

    PubMed

    Routhu, Nanda Kishore; Byrareddy, Siddappa N

    2017-03-27

    The Zika virus (ZIKV) is a newly emerging pathogen that has resulted in a worldwide epidemic. It primarily spreads either through infected Aedes aegypti or Aedes albopictus mosquitos leading to severe neurological disorders such as microcephaly and Guillain-Barré syndrome in susceptible individuals. The mode of ZIKV entry into specific cell types such as: epidermal keratinocytes, fibroblasts, immature dendritic cells (iDCs), and stem-cell-derived human neural progenitors has been determined through its major surface envelope glycoprotein. It has been known that oligosaccharides that are covalently linked to viral envelope proteins are crucial in defining host-virus interactions. However, the role of sugars/glycans in exploiting host-immune mechanisms and aiding receptor-mediated virus entry is not well defined. Therefore, this review focuses on host-pathogen interactions to better understand ZIKV pathogenesis.

  3. Theoretical prediction of the host-guest interactions between novel photoresponsive nanorings and C60: a strategy for facile encapsulation and release of fullerene.

    PubMed

    Yuan, Kun; Dang, Jing-Shuang; Guo, Yi-Jun; Zhao, Xiang

    2015-03-30

    A series of photoresponsive-group-containing nanorings hosts with 12∼14 Å in diameter is designed by introducing different number of azo groups as the structural composition units. And the host-guest interactions between fullerene C60 and those nanoring hosts were investigated theoretically at M06-2X/6-31G(d)//M06-L/MIDI! and wB97X-D/6-31G(d) levels. Analysis on geometrical characteristics and host-guest binding energies revealed that the designed nanoring molecule (labeled as 7) which is composed by seven azo groups and seven phenyls is the most feasible host for encapsulation of C60 guest among all candidates. Moreover, inferring from the simulated UV-vis-NIR spectroscopy, the C60 guest could be facilely released from the cavity of the host 7 via configuration transformation between trans-form and cis-form of the host under the 563 nm photoirradiation. Additionally, the frontier orbital features, weak interaction regions, infrared, and NMR spectra of the C60@7 host-guest complex have also been investigated theoretically.

  4. Early dynamics of guest-host interaction in dye-doped liquid crystalline materials.

    PubMed

    Truong, Thai V; Xu, Lei; Shen, Y R

    2003-05-16

    We have studied in detail the early dynamics of laser-induced molecular reorientation in a dye-doped liquid crystalline (LC) medium that exhibits a significant enhancement of the optical Kerr nonlinearity due to guest-host interaction. Experimental results agree quantitatively with theory based on a model in which the anisotropic dye excitation helps reorient the LC molecules through a mean-field intermolecular interaction.

  5. Tick Genome Assembled: New Opportunities for Research on Tick-Host-Pathogen Interactions

    PubMed Central

    de la Fuente, José; Waterhouse, Robert M.; Sonenshine, Daniel E.; Roe, R. Michael; Ribeiro, Jose M.; Sattelle, David B.; Hill, Catherine A.

    2016-01-01

    As tick-borne diseases are on the rise, an international effort resulted in the sequence and assembly of the first genome of a tick vector. This result promotes research on comparative, functional and evolutionary genomics and the study of tick-host-pathogen interactions to improve human, animal and ecosystem health on a global scale. PMID:27695689

  6. Sequence-based analysis of the genus Ruminococcus resolves its phylogeny and reveals strong host association

    PubMed Central

    La Reau, Alex J.; Meier-Kolthoff, Jan P.

    2016-01-01

    It has become increasingly clear that the composition of mammalian gut microbial communities is substantially diet driven. These microbiota form intricate mutualisms with their hosts, which have profound implications on overall health. For example, many gut microbes are involved in the conversion of host-ingested dietary polysaccharides into host-usable nutrients. One group of important gut microbial symbionts are bacteria in the genus Ruminococcus. Originally isolated from the bovine rumen, ruminococci have been found in numerous mammalian hosts, including other ruminants, and non-ruminants such as horses, pigs and humans. All ruminococci require fermentable carbohydrates for growth, and their substrate preferences appear to be based on the diet of their particular host. Most ruminococci that have been studied are those capable of degrading cellulose, much less is known about non-cellulolytic non-ruminant-associated species, and even less is known about the environmental distribution of ruminococci as a whole. Here, we capitalized on the wealth of publicly available 16S rRNA gene sequences, genomes and large-scale microbiota studies to both resolve the phylogenetic placement of described species in the genus Ruminococcus, and further demonstrate that this genus has largely unexplored diversity and a staggering host distribution. We present evidence that ruminococci are predominantly associated with herbivores and omnivores, and our data supports the hypothesis that very few ruminococci are found consistently in non-host-associated environments. This study not only helps to resolve the phylogeny of this important genus, but also provides a framework for understanding its distribution in natural systems. PMID:28348838

  7. Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis

    PubMed Central

    de Oliveira, Haroldo C.; Assato, Patrícia A.; Marcos, Caroline M.; Scorzoni, Liliana; de Paula E Silva, Ana C. A.; Da Silva, Julhiany De Fátima; Singulani, Junya de Lacorte; Alarcon, Kaila M.; Fusco-Almeida, Ana M.; Mendes-Giannini, Maria J. S.

    2015-01-01

    Paracoccidioides brasiliensis and P. lutzii are etiologic agents of paracoccidioidomycosis (PCM), an important endemic mycosis in Latin America. During its evolution, these fungi have developed characteristics and mechanisms that allow their growth in adverse conditions within their host through which they efficiently cause disease. This process is multi-factorial and involves host–pathogen interactions (adaptation, adhesion, and invasion), as well as fungal virulence and host immune response. In this review, we demonstrated the glycoproteins and polysaccharides network, which composes the cell wall of Paracoccidioides spp. These are important for the change of conidia or mycelial (26°C) to parasitic yeast (37°C). The morphological switch, a mechanism for the pathogen to adapt and thrive inside the host, is obligatory for the establishment of the infection and seems to be related to pathogenicity. For these fungi, one of the most important steps during the interaction with the host is the adhesion. Cell surface proteins called adhesins, responsible for the first contact with host cells, contribute to host colonization and invasion by mediating this process. These fungi also present the capacity to form biofilm and through which they may evade the host’s immune system. During infection, Paracoccidioides spp. can interact with different host cell types and has the ability to modulate the host’s adaptive and/or innate immune response. In addition, it participates and interferes in the coagulation system and phenomena like cytoskeletal rearrangement and apoptosis. In recent years, Paracoccidioides spp. have had their endemic areas expanding in correlation with the expansion of agriculture. In response, several studies were developed to understand the infection using in vitro and in vivo systems, including alternative non-mammal models. Moreover, new advances were made in treating these infections using both well-established and new antifungal agents. These

  8. Ecological and Genetic Differences between Cacopsylla melanoneura (Hemiptera, Psyllidae) Populations Reveal Species Host Plant Preference

    PubMed Central

    Malagnini, Valeria; Pedrazzoli, Federico; Papetti, Chiara; Cainelli, Christian; Zasso, Rosaly; Gualandri, Valeria; Pozzebon, Alberto; Ioriatti, Claudio

    2013-01-01

    The psyllid Cacopsylla melanoneura is considered one of the vectors of ‘Candidatus Phytoplasma mali’, the causal agent of apple proliferation disease. In Northern Italy, overwintered C. melanoneura adults reach apple and hawthorn around the end of January. Nymph development takes place between March and the end of April. The new generation adults migrate onto conifers around mid-June and come back to the host plant species after overwintering. In this study we investigated behavioural differences, genetic differentiation and gene flow between samples of C. melanoneura collected from the two different host plants. Further analyses were performed on some samples collected from conifers. To assess the ecological differences, host-switching experiments were conducted on C. melanoneura samples collected from apple and hawthorn. Furthermore, the genetic structure of the samples was studied by genotyping microsatellite markers. The examined C. melanoneura samples performed better on their native host plant species. This was verified in terms of oviposition and development of the offspring. Data resulting from microsatellite analysis indicated a low, but statistically significant difference between collected-from-apple and hawthorn samples. In conclusion, both ecological and genetic results indicate a differentiation between C. melanoneura samples associated with the two host plants. PMID:23874980

  9. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing.

    PubMed

    Berry, David; Stecher, Bärbel; Schintlmeister, Arno; Reichert, Jochen; Brugiroux, Sandrine; Wild, Birgit; Wanek, Wolfgang; Richter, Andreas; Rauch, Isabella; Decker, Thomas; Loy, Alexander; Wagner, Michael

    2013-03-19

    The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue and intestinal contents, a separation that is vital for health. Some pathogenic microorganisms as well as members of the commensal intestinal microbiota have been shown to be able to break down these secreted compounds. Our understanding of host-compound degradation by the commensal microbiota has been limited to knowledge about simplified model systems because of the difficulty in studying the complex intestinal ecosystem in vivo. In this study, we introduce an approach that overcomes previous technical limitations and allows us to observe which microbial cells in the intestine use host-derived compounds. We added stable isotope-labeled threonine i.v. to mice and combined fluorescence in situ hybridization with high-resolution secondary ion mass spectrometry imaging to characterize utilization of host proteins by individual bacterial cells. We show that two bacterial species, Bacteroides acidifaciens and Akkermansia muciniphila, are important host-protein foragers in vivo. Using gnotobiotic mice we show that microbiota composition determines the magnitude and pattern of foraging by these organisms, demonstrating that a complex microbiota is necessary in order for this niche to be fully exploited. These results underscore the importance of in vivo studies of intestinal microbiota, and the approach presented in this study will be a powerful tool to address many other key questions in animal and human microbiome research.

  10. Supramolecular polymers constructed by orthogonal self-assembly based on host-guest and metal-ligand interactions.

    PubMed

    Wei, Peifa; Yan, Xuzhou; Huang, Feihe

    2015-02-07

    Supramolecular polymers constructed by orthogonal self-assembly based on host-guest and metal-ligand interactions are attracting increasing attention currently because of their interesting properties and potential applications. Host-guest interactions impart these polymers with good selectivity and convenient enviro-responsiveness, and metal-ligand interactions endow them with various coordination geometries, strong yet tunable coordination binding abilities, as well as magnetic, redox, photophysical, and electrochromic properties. Therefore, supramolecular polymers constructed by orthogonal host-guest and metal-ligand interactions have wide applications in the fields of soft matter, fluorescence sensing, heterocatalysis, electronics, gas storage, etc. In this critical review, we will address the recent development of supramolecular polymeric systems involving metal-ligand interactions and host-guest molecular recognition. Specifically, we classify the related supramolecular polymers depending on the types of macrocyclic hosts, and highlight their intriguing properties originating from the elegant combination of host-guest complexation and metal centers.

  11. Getting What Is Served? Feeding Ecology Influencing Parasite-Host Interactions in Invasive Round Goby Neogobius melanostomus

    PubMed Central

    Emde, Sebastian; Kochmann, Judith; Kuhn, Thomas; Plath, Martin; Klimpel, Sven

    2014-01-01

    Freshwater ecosystems are increasingly impacted by alien invasive species which have the potential to alter various ecological interactions like predator-prey and host-parasite relationships. Here, we simultaneously examined predator-prey interactions and parasitization patterns of the highly invasive round goby (Neogobius melanostomus) in the rivers Rhine and Main in Germany. A total of 350 N. melanostomus were sampled between June and October 2011. Gut content analysis revealed a broad prey spectrum, partly reflecting temporal and local differences in prey availability. For the major food type (amphipods), species compositions were determined. Amphipod fauna consisted entirely of non-native species and was dominated by Dikerogammarus villosus in the Main and Echinogammarus trichiatus in the Rhine. However, the availability of amphipod species in the field did not reflect their relative abundance in gut contents of N. melanostomus. Only two metazoan parasites, the nematode Raphidascaris acus and the acanthocephalan Pomphorhynchus sp., were isolated from N. melanostomus in all months, whereas unionid glochidia were only detected in June and October in fish from the Main. To analyse infection pathways, we examined 17,356 amphipods and found Pomphorhynchus sp. larvae only in D. villosus in the river Rhine at a prevalence of 0.15%. Dikerogammarus villosus represented the most important amphipod prey for N. melanostomus in both rivers but parasite intensities differed between rivers, suggesting that final hosts (large predatory fishes) may influence host-parasite dynamics of N. melanostomus in its introduced range. PMID:25338158

  12. RNA-seq in kinetoplastids: A powerful tool for the understanding of the biology and host-pathogen interactions.

    PubMed

    Patino, Luz Helena; Ramírez, Juan David

    2017-04-01

    The kinetoplastids include a large number of parasites responsible for serious diseases in humans and animals (Leishmania and Trypanosoma brucei) considered endemic in several regions of the world. These parasites are characterized by digenetic life cycles that undergo morphological and genetic changes that allow them to adapt to different microenvironments on their vertebrates and invertebrates hosts. Recent advances in ´omics´ technology, specifically transcriptomics have allowed to reveal aspects associated with such molecular changes. So far, different techniques have been used to evaluate the gene expression profile during the various stages of the life cycle of these parasites and during the host-parasite interactions. However, some of them have serious drawbacks that limit the precise study and full understanding of their transcriptomes. Therefore, recently has been implemented the latest technology (RNA-seq), which overcomes the drawbacks of traditional methods. In this review, studies that so far have used RNA-seq are presented and allowed to expand our knowledge regarding the biology of these parasites and their interactions with their hosts.

  13. The chestnut blight fungus for studies on virus/host and virus/virus interactions: from a natural to a model host.

    PubMed

    Eusebio-Cope, Ana; Sun, Liying; Tanaka, Toru; Chiba, Sotaro; Kasahara, Shin; Suzuki, Nobuhiro

    2015-03-01

    The chestnut blight fungus, Cryphonectria parasitica, is an important plant pathogenic ascomycete. The fungus hosts a wide range of viruses and now has been established as a model filamentous fungus for studying virus/host and virus/virus interactions. This is based on the development of methods for artificial virus introduction and elimination, host genome manipulability, available host genome sequence with annotations, host mutant strains, and molecular tools. Molecular tools include sub-cellular distribution markers, gene expression reporters, and vectors with regulatable promoters that have been long available for unicellular organisms, cultured cells, individuals of animals and plants, and certain filamentous fungi. A comparison with other filamentous fungi such as Neurospora crassa has been made to establish clear advantages and disadvantages of C. parasitica as a virus host. In addition, a few recent studies on RNA silencing vs. viruses in this fungus are introduced.

  14. Insights of Phage-Host Interaction in Hypersaline Ecosystem through Metagenomics Analyses

    PubMed Central

    Motlagh, Amir Mohaghegh; Bhattacharjee, Ananda S.; Coutinho, Felipe H.; Dutilh, Bas E.; Casjens, Sherwood R.; Goel, Ramesh K.

    2017-01-01

    Bacteriophages, as the most abundant biological entities on Earth, place significant predation pressure on their hosts. This pressure plays a critical role in the evolution, diversity, and abundance of bacteria. In addition, phages modulate the genetic diversity of prokaryotic communities through the transfer of auxiliary metabolic genes. Various studies have been conducted in diverse ecosystems to understand phage-host interactions and their effects on prokaryote metabolism and community composition. However, hypersaline environments remain among the least studied ecosystems and the interaction between the phages and prokaryotes in these habitats is poorly understood. This study begins to fill this knowledge gap by analyzing bacteriophage-host interactions in the Great Salt Lake, the largest prehistoric hypersaline lake in the Western Hemisphere. Our metagenomics analyses allowed us to comprehensively identify the bacterial and phage communities with Proteobacteria, Firmicutes, and Bacteroidetes as the most dominant bacterial species and Siphoviridae, Myoviridae, and Podoviridae as the most dominant viral families found in the metagenomic sequences. We also characterized interactions between the phage and prokaryotic communities of Great Salt Lake and determined how these interactions possibly influence the community diversity, structure, and biogeochemical cycles. In addition, presence of prophages and their interaction with the prokaryotic host was studied and showed the possibility of prophage induction and subsequent infection of prokaryotic community present in the Great Salt Lake environment under different environmental stress factors. We found that carbon cycle was the most susceptible nutrient cycling pathways to prophage induction in the presence of environmental stresses. This study gives an enhanced snapshot of phage and prokaryote abundance and diversity as well as their interactions in a hypersaline complex ecosystem, which can pave the way for

  15. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts.

    PubMed

    Otto, Thomas D; Rayner, Julian C; Böhme, Ulrike; Pain, Arnab; Spottiswoode, Natasha; Sanders, Mandy; Quail, Michael; Ollomo, Benjamin; Renaud, François; Thomas, Alan W; Prugnolle, Franck; Conway, David J; Newbold, Chris; Berriman, Matthew

    2014-09-09

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host-parasite interface may have mediated host switching.

  16. Host-parasite interactions that guide red blood cell invasion by malaria parasites

    PubMed Central

    Paul, Aditya S.; Egan, Elizabeth S.; Duraisingh, Manoj T.

    2015-01-01

    Purpose of Review Malaria is caused by the infection and proliferation of parasites from the genus Plasmodium in red blood cells (RBCs). A free Plasmodium parasite, or merozoite, released from an infected RBC must invade another RBC host cell to sustain a blood-stage infection. Here, we review recent advances on RBC invasion by Plasmodium merozoites, focusing on specific molecular interactions between host and parasite. Recent findings Recent work highlights the central role of host-parasite interactions at virtually every stage of RBC invasion by merozoites. Biophysical experiments have for the first time measured the strength of merozoite-RBC attachment during invasion. For P. falciparum, there have been many key insights regarding the invasion ligand PfRh5 in particular, including its influence on host species tropism, a co-crystal structure with its RBC receptor basigin, and its suitability as a vaccine target. For P. vivax, researchers identified the origin and emergence of the parasite from Africa, demonstrating a natural link to the Duffy-negative RBC variant in African populations. For the simian parasite P. knowlesi, zoonotic invasion into human cells is linked to RBC age, which has implications for parasitemia during an infection and thus malaria. Summary New studies of the molecular and cellular mechanisms governing RBC invasion by Plasmodium parasites have shed light on various aspects of parasite biology and host cell tropism; and indicate opportunities for malaria control. PMID:25767956

  17. Amphibian chytridiomycosis: a review with focus on fungus-host interactions.

    PubMed

    Van Rooij, Pascale; Martel, An; Haesebrouck, Freddy; Pasmans, Frank

    2015-11-25

    Amphibian declines and extinctions are emblematic for the current sixth mass extinction event. Infectious drivers of these declines include the recently emerged fungal pathogens Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans (Chytridiomycota). The skin disease caused by these fungi is named chytridiomycosis and affects the vital function of amphibian skin. Not all amphibians respond equally to infection and host responses might range from resistant, over tolerant to susceptible. The clinical outcome of infection is highly dependent on the amphibian host, the fungal virulence and environmental determinants. B. dendrobatidis infects the skin of a large range of anurans, urodeles and caecilians, whereas to date the host range of B. salamandrivorans seems limited to urodeles. So far, the epidemic of B. dendrobatidis is mainly limited to Australian, neotropical, South European and West American amphibians, while for B. salamandrivorans it is limited to European salamanders. Other striking differences between both fungi include gross pathology and thermal preferences. With this review we aim to provide the reader with a state-of-the art of host-pathogen interactions for both fungi, in which new data pertaining to the interaction of B. dendrobatidis and B. salamandrivorans with the host's skin are integrated. Furthermore, we pinpoint areas in which more detailed studies are necessary or which have not received the attention they merit.

  18. Transinfection: a method to investigate Wolbachia-host interactions and control arthropod-borne disease

    PubMed Central

    Hughes, Grant L.; Rasgon, Jason L.

    2014-01-01

    The bacterial endosymbiont Wolbachia manipulates arthropod host biology in numerous ways including sex ratio distortion and differential offspring survival. These bacteria infect a vast array of arthropods, some of which pose serious agricultural and human health threats. Wolbachia-mediated phenotypes such as cytoplasmic incompatibility and/or pathogen interference can be utilized for vector and disease control. However, many medically important vectors and important agricultural species are uninfected or are infected with strains of Wolbachia that do not elicit phenotypes desirable for disease or pest control. The ability to transfer strains of Wolbachia into new hosts (transinfection) can create novel Wolbachia-host associations. Transinfection has two primary benefits. First, Wolbachia-host interactions can be examined to tease apart the influence of the host and bacteria on phenotypes. Secondly, desirable phenotypes induced by Wolbachia in a particular insect can be transferred to another recipient host. This can allow for manipulation of insect populations that transmit pathogens or detrimentally affect agriculture. As such, transinfection is a valuable tool to explore Wolbachia biology and control arthropod-borne disease. This review summarizes what is currently known about Wolbachia transinfection methods and applications. We also provide a comprehensive list of published successful and unsuccessful Wolbachia transinfection attempts. PMID:24329998

  19. Transinfection: a method to investigate Wolbachia-host interactions and control arthropod-borne disease.

    PubMed

    Hughes, G L; Rasgon, J L

    2014-04-01

    The bacterial endosymbiont Wolbachia manipulates arthropod host biology in numerous ways, including sex ratio distortion and differential offspring survival. These bacteria infect a vast array of arthropods, some of which pose serious agricultural and human health threats. Wolbachia-mediated phenotypes such as cytoplasmic incompatibility and/or pathogen interference can be used for vector and disease control; however, many medically important vectors and important agricultural species are uninfected or are infected with strains of Wolbachia that do not elicit phenotypes desirable for disease or pest control. The ability to transfer strains of Wolbachia into new hosts (transinfection) can create novel Wolbachia-host associations. Transinfection has two primary benefits. First, Wolbachia-host interactions can be examined to tease apart the influence of the host and bacteria on phenotypes. Second, desirable phenotypes induced by Wolbachia in a particular insect can be transferred to another recipient host. This can allow the manipulation of insect populations that transmit pathogens or detrimentally affect agriculture. As such, transinfection is a valuable tool to explore Wolbachia biology and control arthropod-borne disease. The present review summarizes what is currently known about Wolbachia transinfection methods and applications. We also provide a comprehensive list of published successful and unsuccessful Wolbachia transinfection attempts.

  20. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.

    PubMed

    Baskerville, Scott; Bartel, David P

    2005-03-01

    MicroRNAs (miRNAs) are short endogenous RNAs known to post-transcriptionally repress gene expression in animals and plants. A microarray profiling survey revealed the expression patterns of 175 human miRNAs across 24 different human organs. Our results show that proximal pairs of miRNAs are generally coexpressed. In addition, an abrupt transition in the correlation between pairs of expressed miRNAs occurs at a distance of 50 kb, implying that miRNAs separated by <50 kb typically derive from a common transcript. Some microRNAs are within the introns of host genes. Intronic miRNAs are usually coordinately expressed with their host gene mRNA, implying that they also generally derive from a common transcript, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic miRNAs.

  1. Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin.

    PubMed

    Marvig, Rasmus Lykke; Damkiær, Søren; Khademi, S M Hossein; Markussen, Trine M; Molin, Søren; Jelsbak, Lars

    2014-05-06

    ABSTRACT Pseudomonas aeruginosa airway infections are a major cause of mortality and morbidity of cystic fibrosis (CF) patients. In order to persist, P. aeruginosa depends on acquiring iron from its host, and multiple different iron acquisition systems may be active during infection. This includes the pyoverdine siderophore and the Pseudomonas heme utilization (phu) system. While the regulation and mechanisms of several iron-scavenging systems are well described, it is not clear whether such systems are targets for selection during adaptation of P. aeruginosa to the host environment. Here we investigated the within-host evolution of the transmissible P. aeruginosa DK2 lineage. We found positive selection for promoter mutations leading to increased expression of the phu system. By mimicking conditions of the CF airways in vitro, we experimentally demonstrate that increased expression of phuR confers a growth advantage in the presence of hemoglobin, thus suggesting that P. aeruginosa evolves toward iron acquisition from hemoglobin. To rule out that this adaptive trait is specific to the DK2 lineage, we inspected the genomes of additional P. aeruginosa lineages isolated from CF airways and found similar adaptive evolution in two distinct lineages (DK1 and PA clone C). Furthermore, in all three lineages, phuR promoter mutations coincided with the loss of pyoverdine production, suggesting that within-host adaptation toward heme utilization is triggered by the loss of pyoverdine production. Targeting heme utilization might therefore be a promising strategy for the treatment of P. aeruginosa infections in CF patients. IMPORTANCE Most bacterial pathogens depend on scavenging iron within their hosts, which makes the battle for iron between pathogens and hosts a hallmark of infection. Accordingly, the ability of the opportunistic pathogen Pseudomonas aeruginosa to cause chronic infections in cystic fibrosis (CF) patients also depends on iron-scavenging systems. While

  2. Olfactory Cues, Visual Cues, and Semiochemical Diversity Interact During Host Location by Invasive Forest Beetles.

    PubMed

    Kerr, Jessica L; Kelly, Dave; Bader, Martin K-F; Brockerhoff, Eckehard G

    2017-01-01

    Plant-feeding insects use visual and olfactory cues (shape, color, plant volatiles) for host location, but the relative importance of different cues and interactions with non-host-plant volatiles in ecosystems of varying plant biodiversity is unclear for most species. We studied invasive bark beetles and wood borers associated with pine trees to characterize interactions among color, host and non-host volatiles, by employing traps that mimic tree trunks. Cross-vane flight intercept traps (black, green, red, white, yellow, clear) and black funnel traps were used with and without attractants (α-pinene + ethanol), repellents (non-host green leaf volatiles, 'GLV'), and attractant/repellent combinations in four pine forests in New Zealand. We trapped 274,594 Hylurgus ligniperda, 7842 Hylastes ater, and 16,301 Arhopalus ferus. Trap color, attractant, and color × attractant effects were highly significant. Overall, black and red traps had the highest catches, irrespective of the presence of attractants. Alpha-pinene plus ethanol increased trap catch of H. ligniperda 200-fold but only 6-fold for H. ater and 2-fold for A. ferus. Green leaf volatiles had a substantial repellent effect on trap catch of H. ligniperda but less on H. ater and A. ferus. Attack by H. ligniperda was halved when logs were treated with GLV, and a similar effect was observed when logs were placed among broadleaved understory shrubs emitting GLV. Overall, H. ligniperda was most strongly affected by the olfactory cues used, whereas H. ater and A. ferus were more strongly affected by visual cues. Collectively, the results support the semiochemical diversity hypothesis, indicating that non-host plant volatiles from diverse plant communities or artificial dispensers can contribute to resistance against herbivores by partly disrupting host location.

  3. Single-cell genomics-based analysis of virus–host interactions in marine surface bacterioplankton

    DOE PAGES

    Labonté, Jessica M.; Swan, Brandon K.; Poulos, Bonnie; ...

    2015-04-07

    Viral infections dynamically alter the composition and metabolic potential of marine microbial communities and the evolutionary trajectories of host populations with resulting feedback on biogeochemical cycles. It is quite possible that all microbial populations in the ocean are impacted by viral infections. Our knowledge of virus–host relationships, however, has been limited to a minute fraction of cultivated host groups. Here, we utilized single-cell sequencing to obtain genomic blueprints of viruses inside or attached to individual bacterial and archaeal cells captured in their native environment, circumventing the need for host and virus cultivation. Furthermore, a combination of comparative genomics, metagenomic fragmentmore » recruitment, sequence anomalies and irregularities in sequence coverage depth and genome recovery were utilized to detect viruses and to decipher modes of virus–host interactions. Members of all three tailed phage families were identified in 20 out of 58 phylogenetically and geographically diverse single amplified genomes (SAGs) of marine bacteria and archaea. At least four phage–host interactions had the characteristics of late lytic infections, all of which were found in metabolically active cells. One virus had genetic potential for lysogeny. Our findings include first known viruses of Thaumarchaeota, Marinimicrobia, Verrucomicrobia and Gammaproteobacteria clusters SAR86 and SAR92. Viruses were also found in SAGs of Alphaproteobacteria and Bacteroidetes. A high fragment recruitment of viral metagenomic reads confirmed that most of the SAG-associated viruses are abundant in the ocean. This study demonstrates that single-cell genomics, in conjunction with sequence-based computational tools, enable in situ, cultivation-independent insights into host–virus interactions in complex microbial communities.« less

  4. Single-cell genomics-based analysis of virus–host interactions in marine surface bacterioplankton

    SciTech Connect

    Labonté, Jessica M.; Swan, Brandon K.; Poulos, Bonnie; Luo, Haiwei; Koren, Sergey; Hallam, Steven J.; Sullivan, Matthew B.; Woyke, Tanja; Eric Wommack, K.; Stepanauskas, Ramunas

    2015-04-07

    Viral infections dynamically alter the composition and metabolic potential of marine microbial communities and the evolutionary trajectories of host populations with resulting feedback on biogeochemical cycles. It is quite possible that all microbial populations in the ocean are impacted by viral infections. Our knowledge of virus–host relationships, however, has been limited to a minute fraction of cultivated host groups. Here, we utilized single-cell sequencing to obtain genomic blueprints of viruses inside or attached to individual bacterial and archaeal cells captured in their native environment, circumventing the need for host and virus cultivation. Furthermore, a combination of comparative genomics, metagenomic fragment recruitment, sequence anomalies and irregularities in sequence coverage depth and genome recovery were utilized to detect viruses and to decipher modes of virus–host interactions. Members of all three tailed phage families were identified in 20 out of 58 phylogenetically and geographically diverse single amplified genomes (SAGs) of marine bacteria and archaea. At least four phage–host interactions had the characteristics of late lytic infections, all of which were found in metabolically active cells. One virus had genetic potential for lysogeny. Our findings include first known viruses of Thaumarchaeota, Marinimicrobia, Verrucomicrobia and Gammaproteobacteria clusters SAR86 and SAR92. Viruses were also found in SAGs of Alphaproteobacteria and Bacteroidetes. A high fragment recruitment of viral metagenomic reads confirmed that most of the SAG-associated viruses are abundant in the ocean. This study demonstrates that single-cell genomics, in conjunction with sequence-based computational tools, enable in situ, cultivation-independent insights into host–virus interactions in complex microbial communities.

  5. Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions*

    PubMed Central

    Memišević, Vesna; Zavaljevski, Nela; Pieper, Rembert; Rajagopala, Seesandra V.; Kwon, Keehwan; Townsend, Katherine; Yu, Chenggang; Yu, Xueping; DeShazer, David; Reifman, Jaques; Wallqvist, Anders

    2013-01-01

    Burkholderia mallei is an infectious intracellular pathogen whose virulence and resistance to antibiotics makes it a potential bioterrorism agent. Given its genetic origin as a commensal soil organism, it is equipped with an extensive and varied set of adapted mechanisms to cope with and modulate host-cell environments. One essential virulence mechanism constitutes the specialized secretion systems that are designed to penetrate host-cell membranes and insert pathogen proteins directly into the host cell's cytosol. However, the secretion systems' proteins and, in particular, their host targets are largely uncharacterized. Here, we used a combined in silico, in vitro, and in vivo approach to identify B. mallei proteins required for pathogenicity. We used bioinformatics tools, including orthology detection and ab initio predictions of secretion system proteins, as well as published experimental Burkholderia data to initially select a small number of proteins as putative virulence factors. We then used yeast two-hybrid assays against normalized whole human and whole murine proteome libraries to detect and identify interactions among each of these bacterial proteins and host proteins. Analysis of such interactions provided both verification of known virulence factors and identification of three new putative virulence proteins. We successfully created insertion mutants for each of these three proteins using the virulent B. mallei ATCC 23344 strain. We exposed BALB/c mice to mutant strains and the wild-type strain in an aerosol challenge model using lethal B. mallei doses. In each set of experiments, mice exposed to mutant strains survived for the 21-day duration of the experiment, whereas mice exposed to the wild-type strain rapidly died. Given their in vivo role in pathogenicity, and based on the yeast two-hybrid interaction data, these results point to the importance of these pathogen proteins in modulating host ubiquitination pathways, phagosomal escape, and actin

  6. Nearest-neighbor interactions, habitat fragmentation, and the persistence of host-pathogen systems.

    PubMed

    Wodarz, Dominik; Sun, Zhiying; Lau, John W; Komarova, Natalia L

    2013-09-01

    Spatial interactions are known to promote stability and persistence in enemy-victim interactions if instability and extinction occur in well-mixed settings. We investigate the effect of spatial interactions in the opposite case, where populations can persist in well-mixed systems. A stochastic agent-based model of host-pathogen dynamics is considered that describes nearest-neighbor interactions in an undivided habitat. Contrary to previous notions, we find that in this setting, spatial interactions in fact promote extinction. The reason is that, in contrast to the mass-action system, the outcome of the nearest-neighbor model is governed by dynamics in small "local neighborhoods." This is an abstraction that describes interactions in a minimal grid consisting of an individual plus its nearest neighbors. The small size of this characteristic scale accounts for the higher extinction probabilities. Hence, nearest-neighbor interactions in a continuous habitat lead to outcomes reminiscent of a fragmented habitat, which is underlined further with a metapopulation model that explicitly assumes habitat fragmentation. Beyond host-pathogen dynamics, axiomatic modeling shows that our results hold for generic enemy-victim interactions under specified assumptions. These results are used to interpret a set of published experiments that provide a first step toward model testing and are discussed in the context of the literature.

  7. Use of high-throughput mass spectrometry to elucidate host pathogen interactions in Salmonella

    SciTech Connect

    Rodland, Karin D.; Adkins, Joshua N.; Ansong, Charles; Chowdhury, Saiful M.; Manes, Nathan P.; Shi, Liang; Yoon, Hyunjin; Smith, Richard D.; Heffron, Fred

    2008-12-01

    Capabilities in mass spectrometry are evolving rapidly, with recent improvements in sensitivity, data analysis, and most important, from the standpoint of this review, much higher throughput allowing analysis of many samples in a single day. This short review describes how these improvements in mass spectrometry can be used to dissect host-pathogen interactions using Salmonella as a model system. This approach enabled direct identification of the majority of annotated Salmonella proteins, quantitation of expression changes under various in vitro growth conditions, and new insights into virulence and expression of Salmonella proteins within host cell cells. One of the most significant findings is that a very high percentage of the all annotated genes (>20%) in Salmonella are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several Salmonella virulence regulators that involve protein-protein interactions, suggesting additional functions of these regulators in coordinating virulence expression. Overall high throughput mass spectrometry provides a new view of pathogen-host interactions emphasizing the protein products and defining how protein interactions determine the outcome of infection.

  8. Use of high-throughput mass spectrometry to elucidate host-pathogen interactions in Salmonella

    SciTech Connect

    Rodland, Karin D.; Adkins, Joshua N.; Ansong, Charles; Chowdhury, Saiful M.; Manes, Nathan P.; Shi, Liang; Yoon, Hyunjin; Smith, Richard D.; Heffron, Fred

    2008-12-01

    New improvements to mass spectrometry include increased sensitivity, improvements in analyzing the collected data, and most important, from the standpoint of this review, a much higher throughput allowing analysis of many samples in a single day. This short review describes how host-pathogen interactions can be dissected by mass spectrometry using Salmonella as a model system. The approach allowed direct identification of the majority of annotate Salmonella proteins, how expression changed under various in vitro growth conditions, and how this relates to virulence and expression within host cell cells. One of the most significant findings is that a very high percentage of the all annotated genes (>20%) are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several Salmonella virulence regulators that involve protein-protein interactions suggesting additional functions of the regulator in coordinating virulence expression. Overall high throughput mass spectrometer provides a new view of pathogen-host interaction emphasizing the protein products and defining how protein interactions determine the outcome of infection.

  9. Pathological and therapeutic interactions between bacteriophages, microbes and the host in inflammatory bowel disease

    PubMed Central

    Babickova, Janka; Gardlik, Roman

    2015-01-01

    The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions, a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease (IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition, the immune system and environmental factors. In the recent years, metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review, we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD, host-microbe interactions and therapeutic possibilities using bacteria in IBD. Moreover, an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided. PMID:26525290

  10. Pathological and therapeutic interactions between bacteriophages, microbes and the host in inflammatory bowel disease.

    PubMed

    Babickova, Janka; Gardlik, Roman

    2015-10-28

    The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions, a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease (IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition, the immune system and environmental factors. In the recent years, metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review, we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD, host-microbe interactions and therapeutic possibilities using bacteria in IBD. Moreover, an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided.

  11. Modeling the within-host dynamics of cholera: bacterial-viral interaction.

    PubMed

    Wang, Xueying; Wang, Jin

    2016-12-22

    Novel deterministic and stochastic models are proposed in this paper for the within-host dynamics of cholera, with a focus on the bacterial-viral interaction. The deterministic model is a system of differential equations describing the interaction among the two types of vibrios and the viruses. The stochastic model is a system of Markov jump processes that is derived based on the dynamics of the deterministic model. The multitype branching process approximation is applied to estimate the extinction probability of bacteria and viruses within a human host during the early stage of the bacterial-viral infection. Accordingly, a closed-form expression is derived for the disease extinction probability, and analytic estimates are validated with numerical simulations. The local and global dynamics of the bacterial-viral interaction are analysed using the deterministic model, and the result indicates that there is a sharp disease threshold characterized by the basic reproduction number [Formula: see text]: if [Formula: see text], vibrios ingested from the environment into human body will not cause cholera infection; if [Formula: see text], vibrios will grow with increased toxicity and persist within the host, leading to human cholera. In contrast, the stochastic model indicates, more realistically, that there is always a positive probability of disease extinction within the human host.

  12. Ocean acidification and host-pathogen interactions: blue mussels, Mytilus edulis, encountering Vibrio tubiashii.

    PubMed

    Asplund, Maria E; Baden, Susanne P; Russ, Sarah; Ellis, Robert P; Gong, Ningping; Hernroth, Bodil E

    2014-04-01

    Ocean acidification (OA) can shift the ecological balance between interacting organisms. In this study, we have used a model system to illustrate the interaction between a calcifying host organism, the blue mussel Mytilus edulis and a common bivalve bacterial pathogen, Vibrio tubiashii, with organisms being exposed to a level of acidification projected to occur by the end of the 21st century. OA exposures of the mussels were carried out in relative long-term (4 months) and short-term (4 days) experiments. We found no effect of OA on the culturability of V. tubiashii, in broth or in seawater. OA inhibited mussel shell growth and impaired crystalline shell structures but did not appear to affect mussel immune parameters (i.e haemocyte counts and phagocytotic capacity). Despite no evident impact on host immunity or growth and virulence of the pathogen, V. tubiashii was clearly more successful in infecting mussels exposed to long-term OA compared to those maintained under ambient conditions. Moreover, OA exposed V. tubiashii increased their viability when exposed to haemocytes of OA-treated mussel. Our findings suggest that even though host organisms may have the capacity to cope with periods of OA, these conditions may alter the outcome of host-pathogen interactions, favouring the success of the latter.

  13. Where in the Cell Are You? Probing HIV-1 Host Interactions through Advanced Imaging Techniques

    PubMed Central

    Dirk, Brennan S.; Van Nynatten, Logan R.; Dikeakos, Jimmy D.

    2016-01-01

    Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell–cell transmission and cell–free viral transmission. Moreover, powerful methods such as Forster resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) have shed light on the protein-protein interactions HIV-1 engages within the host to hijack the cellular machinery. Specific advancements in live cell imaging in combination with the use of multicolor viral particles have become indispensable to unravelling the dynamic nature of these virus-host interactions. In the current review, we outline novel imaging methods that have been used to study the HIV-1 lifecycle and highlight advancements in the cell culture models developed to enhance our understanding of the HIV-1 lifecycle. PMID:27775563

  14. Where in the Cell Are You? Probing HIV-1 Host Interactions through Advanced Imaging Techniques.

    PubMed

    Dirk, Brennan S; Van Nynatten, Logan R; Dikeakos, Jimmy D

    2016-10-19

    Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell-cell transmission and cell-free viral transmission. Moreover, powerful methods such as Forster resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) have shed light on the protein-protein interactions HIV-1 engages within the host to hijack the cellular machinery. Specific advancements in live cell imaging in combination with the use of multicolor viral particles have become indispensable to unravelling the dynamic nature of these virus-host interactions. In the current review, we outline novel imaging methods that have been used to study the HIV-1 lifecycle and highlight advancements in the cell culture models developed to enhance our understanding of the HIV-1 lifecycle.

  15. Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission

    PubMed Central

    Howe, Kevin; Fish, Tara; Smith, Dawn; Gildow, Fredrick; MacCoss, Michael J.; Thannhauser, Theodore W.; Gray, Stewart M.

    2012-01-01

    Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions. PMID:23118947

  16. Discovery and targeted LC-MS/MS of purified polerovirus reveals differences in the virus-host interactome associated with altered aphid transmission.

    PubMed

    Cilia, Michelle; Peter, Kari A; Bereman, Michael S; Howe, Kevin; Fish, Tara; Smith, Dawn; Gildow, Fredrick; MacCoss, Michael J; Thannhauser, Theodore W; Gray, Stewart M

    2012-01-01

    Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.

  17. Tailoring biomaterial surface properties to modulate host-implant interactions: implication in cardiovascular and bone therapy

    PubMed Central

    Pacelli, Settimio; Manoharan, Vijayan; Desalvo, Anna; Lomis, Nikita; Jodha, Kartikeya Singh

    2016-01-01

    Host body response to a foreign medical device plays a critical role in defining its fate post implantation. It is thus important to control host-material interactions by designing innovative implant surfaces. In the recent years, biochemical and topographical features have been explored as main target to produce this new type of bioinert or bioresponsive implants. The review discusses specific biofunctional materials and strategies to achieve a precise control over implant surface properties and presents possible solutions to develop next generation of implants, particularly in the fields of bone and cardiovascular therapy. PMID:27630769

  18. Comparative genomics reveals genes significantly associated with woody hosts in the plant pathogen Pseudomonas syringae

    PubMed Central

    Laue, Bridget E.; Sharp, Paul M.; Green, Sarah

    2016-01-01

    Summary The diversification of lineages within Pseudomonas syringae has involved a number of adaptive shifts from herbaceous hosts onto various species of tree, resulting in the emergence of highly destructive diseases such as bacterial canker of kiwi and bleeding canker of horse chestnut. This diversification has involved a high level of gene gain and loss, and these processes are likely to play major roles in the adaptation of individual lineages onto their host plants. In order to better understand the evolution of P. syringae onto woody plants, we have generated de novo genome sequences for 26 strains from the P. syringae species complex that are pathogenic on a range of woody species, and have looked for statistically significant associations between gene presence and host type (i.e. woody or herbaceous) across a phylogeny of 64 strains. We have found evidence for a common set of genes associated with strains that are able to colonize woody plants, suggesting that divergent lineages have acquired similarities in genome composition that may form the genetic basis of their adaptation to woody hosts. We also describe in detail the gain, loss and rearrangement of specific loci that may be functionally important in facilitating this adaptive shift. Overall, our analyses allow for a greater understanding of how gene gain and loss may contribute to adaptation in P. syringae. PMID:27145446

  19. Molecular phylogeny of the bivalve superfamily Galeommatoidea (Heterodonta, Veneroida) reveals dynamic evolution of symbiotic lifestyle and interphylum host switching

    PubMed Central

    2012-01-01

    Background Galeommatoidea is a superfamily of bivalves that exhibits remarkably diverse lifestyles. Many members of this group live attached to the body surface or inside the burrows of other marine invertebrates, including crustaceans, holothurians, echinoids, cnidarians, sipunculans and echiurans. These symbiotic species exhibit high host specificity, commensal interactions with hosts, and extreme morphological and behavioral adaptations to symbiotic life. Host specialization to various animal groups has likely played an important role in the evolution and diversification of this bivalve group. However, the evolutionary pathway that led to their ecological diversity is not well understood, in part because of their reduced and/or highly modified morphologies that have confounded traditional taxonomy. This study elucidates the taxonomy of the Galeommatoidea and their evolutionary history of symbiotic lifestyle based on a molecular phylogenic analysis of 33 galeommatoidean and five putative galeommatoidean species belonging to 27 genera and three families using two nuclear ribosomal genes (18S and 28S ribosomal DNA) and a nuclear (histone H3) and mitochondrial (cytochrome oxidase subunit I) protein-coding genes. Results Molecular phylogeny recovered six well-supported major clades within Galeommatoidea. Symbiotic species were found in all major clades, whereas free-living species were grouped into two major clades. Species symbiotic with crustaceans, holothurians, sipunculans, and echiurans were each found in multiple major clades, suggesting that host specialization to these animal groups occurred repeatedly in Galeommatoidea. Conclusions Our results suggest that the evolutionary history of host association in Galeommatoidea has been remarkably dynamic, involving frequent host switches between different animal phyla. Such an unusual pattern of dynamic host switching is considered to have resulted from their commensalistic lifestyle, in which they maintain filter

  20. HPIDB 2.0: a curated database for host-pathogen interactions.

    PubMed

    Ammari, Mais G; Gresham, Cathy R; McCarthy, Fiona M; Nanduri, Bindu

    2016-01-01

    Identification and analysis of host-pathogen interactions (HPI) is essential to study infectious diseases. However, HPI data are sparse in existing molecular interaction databases, especially for agricultural host-pathogen systems. Therefore, resources that annotate, predict and display the HPI that underpin infectious diseases are critical for developing novel intervention strategies. HPIDB 2.0 (http://www.agbase.msstate.edu/hpi/main.html) is a resource for HPI data, and contains 45, 238 manually curated entries in the current release. Since the first description of the database in 2010, multiple enhancements to HPIDB data and interface services were made that are described here. Notably, HPIDB 2.0 now provides targeted biocuration of molecular interaction data. As a member of the International Molecular Exchange consortium, annotations provided by HPIDB 2.0 curators meet community standards to provide detailed contextual experimental information and facilitate data sharing. Moreover, HPIDB 2.0 provides access to rapidly available community annotations that capture minimum molecular interaction information to address immediate researcher needs for HPI network analysis. In addition to curation, HPIDB 2.0 integrates HPI from existing external sources and contains tools to infer additional HPI where annotated data are scarce. Compared to other interaction databases, our data collection approach ensures HPIDB 2.0 users access the most comprehensive HPI data from a wide range of pathogens and their hosts (594 pathogen and 70 host species, as of February 2016). Improvements also include enhanced search capacity, addition of Gene Ontology functional information, and implementation of network visualization. The changes made to HPIDB 2.0 content and interface ensure that users, especially agricultural researchers, are able to easily access and analyse high quality, comprehensive HPI data. All HPIDB 2.0 data are updated regularly, are publically available for direct

  1. Linear filtering reveals false negatives in species interaction data

    PubMed Central

    Stock, Michiel; Poisot, Timothée; Waegeman, Willem; De Baets, Bernard

    2017-01-01

    Species interaction datasets, often represented as sparse matrices, are usually collected through observation studies targeted at identifying species interactions. Due to the extensive required sampling effort, species interaction datasets usually contain many false negatives, often leading to bias in derived descriptors. We show that a simple linear filter can be used to detect false negatives by scoring interactions based on the structure of the interaction matrices. On 180 different datasets of various sizes, sparsities and ecological interaction types, we found that on average in about 75% of the cases, a false negative interaction got a higher score than a true negative interaction. Furthermore, we show that this filter is very robust, even when the interaction matrix contains a very large number of false negatives. Our results demonstrate that unobserved interactions can be detected in species interaction datasets, even without resorting to information about the species involved. PMID:28383526

  2. 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.

  3. Bioluminescence to reveal structure and interaction of coastal planktonic communities

    NASA Astrophysics Data System (ADS)

    Moline, Mark A.; Blackwell, Shelley M.; Case, James F.; Haddock, Steven H. D.; Herren, Christen M.; Orrico, Cristina M.; Terrill, Eric

    2009-02-01

    Ecosystem function will in large part be determined by functional groups present in biological communities. The simplest distinction with respect to functional groups of an ecosystem is the differentiation between primary and secondary producers. A challenge thus far has been to examine these groups simultaneously with sufficient temporal and spatial resolution for observations to be relevant to the scales of change in coastal oceans. This study takes advantage of general differences in the bioluminescence flash kinetics between planktonic dinoflagellates and zooplankton to measure relative abundances of the two groups within the same-time space volume. This novel approach for distinguishing these general classifications using a single sensor is validated using fluorescence data and exclusion experiments. The approach is then applied to data collected from an autonomous underwater vehicle surveying >500 km in Monterey Bay and San Luis Obispo Bay, CA during the summers of 2002-2004. The approach also reveals that identifying trophic interaction between the two planktonic communities may also be possible.

  4. Aggregation of Infective Stages of Parasites as an Adaptation and Its Implications for the Study of Parasite-Host Interactions.

    PubMed

    Morrill, André; Forbes, Mark R

    2016-02-01

    The causes and consequences of aggregation among conspecifics have received much attention. For infecting macroparasites, causes include variation among hosts in susceptibility and whether infective stages are aggregated in the environment. Here, we link these two phenomena and explore whether aggregation of infective stages in the environment is adaptive to parasites encountering host condition-linked defenses and what effect such aggregations have for parasite-host interactions. Using simulation models, we show that parasite fitness is increased by aggregates attacking a host, particularly when investment into defenses is high. The fitness benefit of aggregation remains despite inclusion of factors that should curb the benefits of aggregation, namely, mortality of low-condition hosts (those hosts expected to be most susceptible to parasitism) and costs of high coinfection. For sample sizes common in studies, aggregation of infective stages reduces the likelihood of detecting host condition-parasitism relations, even when host condition is the only other factor in models affecting parasitism. Thus, it is not surprising that the expected inverse relations between host condition and parasitism, commonly a premise in studies of parasite-host interactions, are inconsistently found. An understanding of how parasites encounter hosts is thus needed for developing theory for parasite-host ecological and evolutionary interactions.

  5. Commensal Viruses of Mosquitoes: Host Restriction, Transmission, and Interaction with Arboviral Pathogens

    PubMed Central

    Hall, Roy A.; Bielefeldt-Ohmann, Helle; McLean, Breeanna J.; O’Brien, Caitlin A.; Colmant, Agathe M.G.; Piyasena, Thisun B.H.; Harrison, Jessica J.; Newton, Natalee D.; Barnard, Ross T.; Prow, Natalie A.; Deerain, Joshua M.; Mah, Marcus G.K.Y.; Hobson-Peters, Jody

    2016-01-01

    Recent advances in virus detection strategies and deep sequencing technologies have enabled the identification of a multitude of new viruses that persistently infect mosquitoes but do not infect vertebrates. These are usually referred to as insect-specific viruses (ISVs). These novel viruses have generated considerable interest in their modes of transmission, persistence in mosquito populations, the mechanisms that restrict their host range to mosquitoes, and their interactions with pathogens transmissible by the same mosquito. In this article, we discuss studies in our laboratory and others that demonstrate that many ISVs are efficiently transmitted directly from the female mosquito to their progeny via infected eggs, and, moreover, that persistent infection of mosquito cell cultures or whole mosquitoes with ISVs can restrict subsequent infection, replication, and transmission of some mosquito-borne viral pathogens. This suggests that some ISVs may act as natural regulators of arboviral transmission. We also discuss viral and host factors that may be responsible for their host restriction. PMID:28096646

  6. Analysis of an in vivo model to study the interaction of host factors with Candida albicans.

    PubMed Central

    Poor, A H; Cutler, J E

    1981-01-01

    Conditions were established under which membrane diffusion chambers surgically implanted into mice could be used to study interactions between host defense factors and Candida albicans within the chambers. Depending on the size of membrane pores, soluble host substances and phagocytic cells entered the chambers during the first 24 h after chamber implantation. By 7 days in vivo, the membranes of chambers appeared impermeable to these host factors. Mouse phagocytic cells were found to be functional within the in vivo chambers whether the cells emigrated to the chambers on their own accord or were placed there before chamber implantation. Opsonic factors such as antibody and complement appeared to be biologically functional within the in vivo chambers. Conditions suitable for harvesting C. albicans from the chambers also were determined. PMID:7014455

  7. Inference of cowpox virus transmission rates between wild rodent host classes using space-time interaction.

    PubMed

    Carslake, David; Bennett, Malcolm; Hazel, Sarah; Telfer, Sandra; Begon, Michael

    2006-04-07

    There have been virtually no studies of 'who acquires infection from whom' in wildlife populations, but patterns of transmission within and between different classes of host are likely to be reflected in the spatiotemporal distribution of infection among those host classes. Here, we use a modified form of K-function analysis to test for space-time interaction among bank voles and wood mice infectious with cowpox virus. There was no evidence for transmission between the two host species, supporting previous evidence that they act as separate reservoirs for cowpox. Among wood mice, results suggested that transmission took place primarily between individuals of the opposite sex, raising the possibility that cowpox is sexually transmitted in this species. Results for bank voles indicated that infected females might be a more important source of infection to either sex than are males. The suggestion of different modes of transmission in the two species is itself consistent with the apparent absence of transmission between species.

  8. Supramolecular chemistry at interfaces: host-guest interactions for fabricating multifunctional biointerfaces.

    PubMed

    Yang, Hui; Yuan, Bin; Zhang, Xi; Scherman, Oren A

    2014-07-15

    CONSPECTUS: Host-guest chemistry can greatly improve the selectivity of biomolecule-ligand binding on account of recognition-directed interactions. In addition, functional structures and the actuation of supramolecular assemblies in molecular systems can be controlled efficiently through various host-guest chemistry. Together, these highly selective, strong yet dynamic interactions can be exploited as an alternative methodology for applications in the field of programmable and controllable engineering of supramolecular soft materials through the reversible binding between complementary components. Many processes in living systems such as biotransformation, transportation of matter, and energy transduction begin with interfacial molecular recognition, which is greatly influenced by various external stimuli at biointerfaces. Detailed investigations about the molecular recognition at interfaces can result in a better understanding of life science, and further guide us in developing new biomaterials and medicines. In order to mimic complicated molecular-recognition systems observed in nature that adapt to changes in their environment, combining host-guest chemistry and surface science is critical for fabricating the next generation of multifunctional biointerfaces with efficient stimuli-responsiveness and good biocompatibility. In this Account, we will summarize some recent progress on multifunctional stimuli-responsive biointerfaces and biosurfaces fabricated by cyclodextrin- or cucurbituril-based host-guest chemistry and highlight their potential applications including drug delivery, bioelectrocatalysis, and reversible adsorption and resistance of peptides, proteins, and cells. In addition, these biointerfaces and biosurfaces demonstrate efficient response toward various external stimuli, such as UV light, pH, redox chemistry, and competitive guests. All of these external stimuli can aid in mimicking the biological stimuli evident in complex biological environments

  9. Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

    SciTech Connect

    Krishnan, A

    2006-08-30

    The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

  10. Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions

    NASA Astrophysics Data System (ADS)

    Rood, Mark T. M.; Spa, Silvia J.; Welling, Mick M.; Ten Hove, Jan Bart; van Willigen, Danny M.; Buckle, Tessa; Velders, Aldrik H.; van Leeuwen, Fijs W. B.

    2017-01-01

    The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.

  11. Complex interactions among host pines and fungi vectored by an invasive bark beetle.

    PubMed

    Lu, Min; Wingfield, Michael J; Gillette, Nancy E; Mori, Sylvia R; Sun, Jiang-Hua

    2010-08-01

    *Recent studies have investigated the relationships between pairs or groups of exotic species to illustrate invasive mechanisms, but most have focused on interactions at a single trophic level. *Here, we conducted pathogenicity tests, analyses of host volatiles and fungal growth tests to elucidate an intricate network of interactions between the host tree, the invasive red turpentine beetle and its fungal associates. *Seedlings inoculated with two strains of Leptographium procerum isolated from Dendroctonus valens in China had significantly longer lesions and higher mortality rates than seedlings inoculated with other fungal isolates. These two strains of L. procerum were significantly more tolerant of 3-carene than all other fungi isolated there, and the infection of Chinese pine (Pinus tabuliformis) seedlings by these two strains enhanced the production and release of 3-carene, the main attractant for D. valens, by the seedlings. *Our results raise the possibility that interactions among the fungal associates of D. valens and their pine hosts in China may confer advantages to these strains of L. procerum and, by extension, to the beetles themselves. These interactions may therefore enhance invasion by the beetle-fungal complex.

  12. Model organism proteomics as a tool for the study of host-microbiome interactions.

    PubMed

    Cassidy, Liam; Tholey, Andreas

    2014-10-01

    All organisms live in constant contact with the microbial world. In recent years it has become evident that these microbial communities are not only responsible for the development of certain diseases, but are also an indispensable factor for homeostasis. The inherent complexity of meta-organisms hampers a straightforward elucidation of the molecular processes regulating the interactions of the host and its microbiome, as well as the influence of exogenic factors, for example, nutrition. Modern approaches such as meta-proteomics are now capable of deciphering the major processes in microbial communities, but the complete analysis of their interactions with their host is still in its infancy. In order to get easier access, the study of nonmammalian model organisms bears great potential. These organisms provide advantages such as reduced complexity, ease of cultivation in great numbers, and amenity to a range of genetic and biochemical manipulations. We highlight the potentials provided by model organism proteomics for the study of host-microbiome interactions and outline major challenges and demands for technological improvements that will be necessary for the understanding of the manifold interactions within meta-organisms.

  13. Environmental influences on virus-host interactions in an Australian subtropical reservoir.

    PubMed

    Säwström, Christin; Pollard, Peter

    2012-02-01

    Viral and prokaryotic interactions in freshwaters have been investigated worldwide but there are few temporal studies in the tropics and none in the sub-tropics. In this 10-month study, we examined temporal changes in virus-host interactions and viral life cycles (lytic versus lysogenic) in relation to the prevailing environmental conditions in a subtropical water reservoir (Wivenhoe) in southeast Queensland, Australia. Heterotrophic prokaryotes and picocyanobacteria were positively correlated with concentrations of viruses throughout the study, indicating the presence of both bacteriophages and cyanophages in the reservoir. The percentage of heterotrophic prokaryotes and picocyanobacteria containing intracellular viruses (FVIC) ranged between 0.2% and 2.4% and did not vary significantly over the 10-month study, whereas lysogenic heterotrophic prokaryotes were only detected in the drier months of June and July. Spearman rank correlation analysis showed that the oxidative-reduction potential (ORP) of the water reservoir influenced the concentrations of viruses, heterotrophic prokaryotes and picocyanobacteria significantly, with low ORP offering a favourable environment for these components. There was a negative relationship between FVIC and rainfall suggesting the associated run-off altered virus-host interactions. Overall, our study provides novel information and inferences on how virus-host interactions in subtropical freshwaters might respond to changes in precipitation predicted to occur with global climate change.

  14. Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions.

    PubMed

    Rood, Mark T M; Spa, Silvia J; Welling, Mick M; Ten Hove, Jan Bart; van Willigen, Danny M; Buckle, Tessa; Velders, Aldrik H; van Leeuwen, Fijs W B

    2017-01-06

    The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or "training" of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.

  15. Local interactions lead to pathogen-driven change to host population dynamics.

    PubMed

    Boots, Michael; Childs, Dylan; Reuman, Daniel C; Mealor, Michael

    2009-10-13

    Individuals tend to interact more strongly with nearby individuals or within particular social groups. Recent theoretical advances have demonstrated that these within-population relationships can have fundamental implications for ecological and evolutionary dynamics. In particular, contact networks are crucial to the spread and evolution of disease. However, the theory remains largely untested experimentally. Here, we manipulate habitat viscosity and thereby the frequency of local interactions in an insect-pathogen model system in which the virus had previously been shown to have little effect on host population dynamics. At high viscosity, the pathogen caused the collapse of dominant and otherwise stable host generation cycles. Modeling shows that this collapse can be explained by an increase in the frequency of intracohort interactions relative to intercohort interactions, leading to more disease transmission. Our work emphasizes that spatial structure can subtly mediate intraspecific competition and the effects of natural enemies. A decrease in dispersal in a population may actually (sometimes rather counterintuitively) intensify the effects of parasites. Broadly, because anthropological and environmental change often cause changes in population mixing, our work highlights the potential for dramatic changes in the effects of parasites on host populations.

  16. Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions

    PubMed Central

    Rood, Mark T. M.; Spa, Silvia J.; Welling, Mick M.; ten Hove, Jan Bart; van Willigen, Danny M.; Buckle, Tessa; Velders, Aldrik H.; van Leeuwen, Fijs W. B.

    2017-01-01

    The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings. PMID:28057918

  17. Dual-color fluorescence imaging of tumor/host interaction with green and red fluorescent proteins

    NASA Astrophysics Data System (ADS)

    Yang, Meng; Amoh, Yasuyuki; Li, Lingna; Baranov, Eugene; Wang, Jin Wei; Jiang, Ping; Moossa, A. R.; Hoffman, Robert M.

    2004-06-01

    Dual-color fluorescence imaging using red fluorescent protein (RFP)-expressing tumors transplanted in green fluorescent protein (GFP) expressing transgenic mice has been shown to be a powerful technology to study tumor-host interaction. Host animals include mice which express the GFP transgene in essentially all cells as well as animals in which the regulatory elements of the stem cell marker nestin drive GFP. The general GFP-transgenic mouse is available in both the normal and athymic nude (nu/nu) background. These models show with great clarity the details of the tumor-stroma interaction especially tumor induced angiogenesis, tumor-infiltrating lymphocytes, stromal fibroblasts and macrophages. GFP-expressing tumor vasculature could be visualized interacting with the RFP-expressing tumor cells transplanted to the nestin-driven GFP transgenic mice which expressed nestin-GFP in nascent blood vessels was shown as a marker of nascent tumor angiogenesis. Dual-color fluorescence imaging, which visualizes the tumor-host interaction by whole-body imaging and at the cellular level in fresh tissues, dramatically expanding previous studies in fixed and stained preparations (1).

  18. Host-guest interaction and structural ordering in polymeric nanoassemblies: Influence of molecular design.

    PubMed

    Antoniuk, Iurii; Plazzotta, Beatrice; Wintgens, Véronique; Volet, Gisèle; Nielsen, Thorbjørn T; Pedersen, Jan Skov; Amiel, Catherine

    2017-02-24

    Host-guest nanoassemblies made from spontaneous self-association of host and guest polymers in aqueous solutions have been studied. The specific motivation behind this work was to clarify the impact of the molecular design of the polymers on the interactions between them and on the inner structure of the resulting nanoassemblies. The polymers were composed of a dextran backbone, functionalized with either pendant β-cyclodextrin (CD) or adamantyl (Ada). Those groups were connected to the backbone either directly or with hydrophilic polyethylene glycol (PEG) spacers. To study the impact of those spacers we have proposed a synthetic pathway to new guest polymers. The latter relied on the use of thiol-substituted dextrans as a scaffold, which is subsequently transformed into PEG-Ada grafted guest polymers via nucleophile-mediated thiol-click reaction. Surface plasmon resonance (SPR) studies evidenced strong mutual affinities between the host and guest polymers and showed that the stoichiometry was close to the ideal one (CD/Ada = 1/1) when PEG spacers were introduced. The structure of the nanoassemblies was studied by a combination of dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). The nature of the individual host or guest polymers has a strong impact on the size and internal structure of the resulting nanoassemblies. The presence of PEG spacers in the polymers led to smaller and less compact nanoassemblies, as evidenced by their large correlation length values (4-20nm compared to 2nm without PEG spacers). At the same time, all types of nanoassemblies appear to have radial density distribution with denser cores and pending polymer chains at the periphery. This study, centered on the influence of the molecular design on the host-guest interactions and structural ordering in polymeric nanoassemblies, will help to tailor host-guest nanoassemblies with attractive drug delivery profiles.

  19. Alterations in the virulence potential of enteric pathogens and bacterial-host cell interactions under simulated microgravity conditions.

    PubMed

    Chopra, V; Fadl, A A; Sha, J; Chopra, S; Galindo, C L; Chopra, A K

    2006-07-01

    Host immune mechanisms were proposed to decline under microgravity conditions during spaceflights, which might result in severe infections in astronauts. Therefore, it was important to investigate the effects of microgravity on infecting organisms and their interaction with host cells. Data showed that simulated microgravity (SMG) conditions markedly increased production of the enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin, which induced fluid secretory responses in a mouse model. SMG also enhanced production of tumor necrosis factor-alpha in murine macrophages infected with enteropathogenic E. coli (EPEC). In a similar fashion, simulated microgravity conditions augmented the invasive potential of Salmonella enterica serovar typhimurium and enhanced production of tumor necrosis-factor alpha in S. typhimurium-infected epithelial cells. Furthermore, coculturing of macrophages and S. typhimurium in a simulated microgravity environment resulted in activation of stress-associated mitogen-activated protein kinase kinase 4. Using the antiorthostatic tail suspension mouse model, which simulates some aspects of microgravity, oral inoculation of S. typhimurium markedly reduced the 50% lethal dose compared to mice infected under normal gravitational conditions. Microarray analysis revealed simulated microgravity-induced alterations in the expression of 22 genes in S. typhimurium, and protein expression profiles were altered in both EPEC and S. typhimurium, based on two-dimensional gel electrophoresis. These studies indicated alterations in the virulence potential of bacteria and in host responses to these pathogens under simulated microgravity conditions, which may represent an important environmental signal. Such studies are essential for better understanding bacterial-host cell interactions, particularly in the context of spaceflights and space habitations of long duration.

  20. Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets

    PubMed Central

    McGarvey, Peter B.; Huang, Hongzhan; Mazumder, Raja; Zhang, Jian; Chen, Yongxing; Zhang, Chengdong; Cammer, Stephen; Will, Rebecca; Odle, Margie; Sobral, Bruno; Moore, Margaret; Wu, Cathy H.

    2009-01-01

    The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten

  1. Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

    PubMed Central

    Gish, Stacey R.; Maier, Ezekiel J.; Haynes, Brian C.; Santiago-Tirado, Felipe H.; Srikanta, Deepa L.; Ma, Cynthia Z.; Li, Lucy X.; Williams, Matthew; Crouch, Erika C.; Khader, Shabaana A.

    2016-01-01

    ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201, RIM101, and SP1. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. PMID:27094327

  2. Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts

    PubMed Central

    Ma, Liang; Chen, Zehua; Huang, Da Wei; Kutty, Geetha; Ishihara, Mayumi; Wang, Honghui; Abouelleil, Amr; Bishop, Lisa; Davey, Emma; Deng, Rebecca; Deng, Xilong; Fan, Lin; Fantoni, Giovanna; Fitzgerald, Michael; Gogineni, Emile; Goldberg, Jonathan M.; Handley, Grace; Hu, Xiaojun; Huber, Charles; Jiao, Xiaoli; Jones, Kristine; Levin, Joshua Z.; Liu, Yueqin; Macdonald, Pendexter; Melnikov, Alexandre; Raley, Castle; Sassi, Monica; Sherman, Brad T.; Song, Xiaohong; Sykes, Sean; Tran, Bao; Walsh, Laura; Xia, Yun; Yang, Jun; Young, Sarah; Zeng, Qiandong; Zheng, Xin; Stephens, Robert; Nusbaum, Chad; Birren, Bruce W.; Azadi, Parastoo; Lempicki, Richard A.; Cuomo, Christina A.; Kovacs, Joseph A.

    2016-01-01

    Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses. PMID:26899007

  3. Prediction of Interactions between Viral and Host Proteins Using Supervised Machine Learning Methods

    PubMed Central

    Barman, Ranjan Kumar; Saha, Sudipto; Das, Santasabuj

    2014-01-01

    Background Viral-host protein-protein interaction plays a vital role in pathogenesis, since it defines viral infection of the host and regulation of the host proteins. Identification of key viral-host protein-protein interactions (PPIs) has great implication for therapeutics. Methods In this study, a systematic attempt has been made to predict viral-host PPIs by integrating different features, including domain-domain association, network topology and sequence information using viral-host PPIs from VirusMINT. The three well-known supervised machine learning methods, such as SVM, Naïve Bayes and Random Forest, which are commonly used in the prediction of PPIs, were employed to evaluate the performance measure based on five-fold cross validation techniques. Results Out of 44 descriptors, best features were found to be domain-domain association and methionine, serine and valine amino acid composition of viral proteins. In this study, SVM-based method achieved better sensitivity of 67% over Naïve Bayes (37.49%) and Random Forest (55.66%). However the specificity of Naïve Bayes was the highest (99.52%) as compared with SVM (74%) and Random Forest (89.08%). Overall, the SVM and Random Forest achieved accuracy of 71% and 72.41%, respectively. The proposed SVM-based method was evaluated on blind dataset and attained a sensitivity of 64%, specificity of 83%, and accuracy of 74%. In addition, unknown potential targets of hepatitis B virus-human and hepatitis E virus-human PPIs have been predicted through proposed SVM model and validated by gene ontology enrichment analysis. Our proposed model shows that, hepatitis B virus “C protein” binds to membrane docking protein, while “X protein” and “P protein” interacts with cell-killing and metabolic process proteins, respectively. Conclusion The proposed method can predict large scale interspecies viral-human PPIs. The nature and function of unknown viral proteins (HBV and HEV), interacting partners of host protein

  4. Endozoicomonas genomes reveal functional adaptation and plasticity in bacterial strains symbiotically associated with diverse marine hosts

    PubMed Central

    Neave, Matthew J.; Michell, Craig T.; Apprill, Amy; Voolstra, Christian R.

    2017-01-01

    Endozoicomonas bacteria are globally distributed and often abundantly associated with diverse marine hosts including reef-building corals, yet their function remains unknown. In this study we generated novel Endozoicomonas genomes from single cells and metagenomes obtained directly from the corals Stylophora pistillata, Pocillopora verrucosa, and Acropora humilis. We then compared these culture-independent genomes to existing genomes of bacterial isolates acquired from a sponge, sea slug, and coral to examine the functional landscape of this enigmatic genus. Sequencing and analysis of single cells and metagenomes resulted in four novel genomes with 60–76% and 81–90% genome completeness, respectively. These data also confirmed that Endozoicomonas genomes are large and are not streamlined for an obligate endosymbiotic lifestyle, implying that they have free-living stages. All genomes show an enrichment of genes associated with carbon sugar transport and utilization and protein secretion, potentially indicating that Endozoicomonas contribute to the cycling of carbohydrates and the provision of proteins to their respective hosts. Importantly, besides these commonalities, the genomes showed evidence for differential functional specificity and diversification, including genes for the production of amino acids. Given this metabolic diversity of Endozoicomonas we propose that different genotypes play disparate roles and have diversified in concert with their hosts. PMID:28094347

  5. Persistence of a dominant bovine lineage of group B Streptococcus reveals genomic signatures of host adaptation.

    PubMed

    Almeida, Alexandre; Alves-Barroco, Cinthia; Sauvage, Elisabeth; Bexiga, Ricardo; Albuquerque, Pedro; Tavares, Fernando; Santos-Sanches, Ilda; Glaser, Philippe

    2016-11-01

    Group B Streptococcus (GBS) is a host-generalist species, most notably causing disease in humans and cattle. However, the differential adaptation of GBS to its two main hosts, and the risk of animal to human infection remain poorly understood. Despite improvements in control measures across Europe, GBS is still one of the main causative agents of bovine mastitis in Portugal. Here, by whole-genome analysis of 150 bovine GBS isolates we discovered that a single CC61 clone is spreading throughout Portuguese herds since at least the early 1990s, having virtually replaced the previous GBS population. Mutations within an iron/manganese transporter were independently acquired by all of the CC61 isolates, underlining a key adaptive strategy to persist in the bovine host. Lateral transfer of bacteriocin production and antibiotic resistance genes also underscored the contribution of the microbial ecology and genetic pool within the bovine udder environment to the success of this clone. Compared to strains of human origin, GBS evolves twice as fast in bovines and undergoes recurrent pseudogenizations of human-adapted traits. Our work provides new insights into the potentially irreversible adaptation of GBS to the bovine environment.

  6. An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function.

    PubMed

    Nounamo, Bernice; Li, Yibo; O'Byrne, Peter; Kearney, Aoife M; Khan, Amir; Liu, Jia

    2017-03-01

    In humans, deleterious mutations in the sterile α motif domain protein 9 (SAMD9) gene are associated with cancer, inflammation, weakening of the immune response, and developmental arrest. However, the biological function of SAMD9 and its sequence-structure relationships remain to be characterized. Previously, we found that an essential host range factor, M062 protein from myxoma virus (MYXV), antagonized the function of human SAMD9. In this study, we examine the interaction between M062 and human SAMD9 to identify regions that are critical to SAMD9 function. We also characterize the in vitro kinetics of the interaction. In an infection assay, exogenous expression of SAMD9 N-terminus leads to a potent inhibition of wild-type MYXV infection. We reason that this effect is due to the sequestration of viral M062 by the exogenously expressed N-terminal SAMD9 region. Our studies reveal the first molecular insight into viral M062-dependent mechanisms that suppress human SAMD9-associated antiviral function.

  7. Insights into the Complexity of Weak Intermolecular Interactions Interfering in Host-Guest Systems.

    PubMed

    Zhang, Dawei; Chatelet, Bastien; Serrano, Eloisa; Perraud, Olivier; Dutasta, Jean-Pierre; Robert, Vincent; Martinez, Alexandre

    2015-10-05

    The recognition properties of heteroditopic hemicryptophane hosts towards anions, cations, and neutral pairs, combining both cation-π and anion-π interaction sites, were investigated to probe the complexity of interfering weak intermolecular interactions. It is suggested from NMR experiments, and supported by CASSCF/CASPT2 calculations, that the binding constants of anions can be modulated by a factor of up to 100 by varying the fluorination sites on the electron-poor aromatic rings. Interestingly, this subtle chemical modification can also reverse the sign of cooperativity in ion-pair recognition. Wavefunction calculations highlight how short- and long-range interactions interfere in this recognition process, suggesting that a disruption of anion-π interactions can occur in the presence of a co-bound cation. Such molecules can be viewed as prototypes for examining complex processes controlled by the competition of weak interactions.

  8. Morphology and its underlying genetic regulation impact the interaction between Cryptococcus neoformans and its hosts.

    PubMed

    Lin, Jianfeng; Idnurm, Alexander; Lin, Xiaorong

    2015-06-01

    Cryptococcus neoformans is a fungus that causes the majority of fatal cryptococcal meningitis cases worldwide. This pathogen is capable of assuming different morphotypes: yeast, pseudohypha, and hypha. The yeast form is the most common cell type observed clinically. The hyphal and pseudohyphal forms are rarely observed in the clinical setting and are considered attenuated in virulence. However, as a ubiquitous environmental pathogen, Cryptococcus interacts with various organisms, and it is known to be parasitic to different hosts. Capitalizing on recent discoveries, morphogenesis regulators were manipulated to examine the impact of cell shape on the cryptococcal interaction with three different host systems: the soil amoeba Acanthamoeba castellanii (a protist), the greater wax moth Galleria mellonella (an insect), and the murine macrophage cell line J774A.1 (mammalian cells). The regulation of Ace2 and morphogenesis (RAM) pathway is a highly conserved pathway among eukaryotes that regulates cytokinesis. Disruption of any of five RAM components in Cryptococcus renders cells constitutively in the pseudohyphal form. The transcription factor Znf2 is the master activator of the yeast to hyphal transition. Deletion of ZNF2 locks cells in the yeast form, while overexpression of this regulator drives hyphal growth. Genetic epistasis analyses indicate that the RAM and the Znf2 pathways regulate distinct aspects of cryptococcal morphogenesis and independently of each other. These investigations using the Cryptococcus RAM and ZNF2 mutants indicate that cell shape, cell size, and likely cell surface properties weigh differently on the outcome of cryptococcal interactions with different hosts. Thus, certain traits evolved in Cryptococcus that are beneficial within one host might be detrimental when a different host is encountered.

  9. Single-cell sequencing provides clues about the host interactions of segmented filamentous bacteria (SFB).

    PubMed

    Pamp, Sünje J; Harrington, Eoghan D; Quake, Stephen R; Relman, David A; Blainey, Paul C

    2012-06-01

    Segmented filamentous bacteria (SFB) are host-specific intestinal symbionts that comprise a distinct clade within the Clostridiaceae, designated Candidatus Arthromitus. SFB display a unique life cycle within the host, involving differentiation into multiple cell types. The latter include filaments that attach intimately to intestinal epithelial cells, and from which "holdfasts" and spores develop. SFB induce a multifaceted immune response, leading to host protection from intestinal pathogens. Cultivation resistance has hindered characterization of these enigmatic bacteria. In the present study, we isolated five SFB filaments from a mouse using a microfluidic device equipped with laser tweezers, generated genome sequences from each, and compared these sequences with each other, as well as to recently published SFB genome sequences. Based on the resulting analyses, SFB appear to be dependent on the host for a variety of essential nutrients. SFB have a relatively high abundance of predicted proteins devoted to cell cycle control and to envelope biogenesis, and have a group of SFB-specific autolysins and a dynamin-like protein. Among the five filament genomes, an average of 8.6% of predicted proteins were novel, including a family of secreted SFB-specific proteins. Four ADP-ribosyltransferase (ADPRT) sequence types, and a myosin-cross-reactive antigen (MCRA) protein were discovered; we hypothesize that they are involved in modulation of host responses. The presence of polymorphisms among mouse SFB genomes suggests the evolution of distinct SFB lineages. Overall, our results reveal several aspects of SFB adaptation to the mammalian intestinal tract.

  10. Single-cell sequencing provides clues about the host interactions of segmented filamentous bacteria (SFB)

    PubMed Central

    Pamp, Sünje J.; Harrington, Eoghan D.; Quake, Stephen R.; Relman, David A.; Blainey, Paul C.

    2012-01-01

    Segmented filamentous bacteria (SFB) are host-specific intestinal symbionts that comprise a distinct clade within the Clostridiaceae, designated Candidatus Arthromitus. SFB display a unique life cycle within the host, involving differentiation into multiple cell types. The latter include filaments that attach intimately to intestinal epithelial cells, and from which “holdfasts” and spores develop. SFB induce a multifaceted immune response, leading to host protection from intestinal pathogens. Cultivation resistance has hindered characterization of these enigmatic bacteria. In the present study, we isolated five SFB filaments from a mouse using a microfluidic device equipped with laser tweezers, generated genome sequences from each, and compared these sequences with each other, as well as to recently published SFB genome sequences. Based on the resulting analyses, SFB appear to be dependent on the host for a variety of essential nutrients. SFB have a relatively high abundance of predicted proteins devoted to cell cycle control and to envelope biogenesis, and have a group of SFB-specific autolysins and a dynamin-like protein. Among the five filament genomes, an average of 8.6% of predicted proteins were novel, including a family of secreted SFB-specific proteins. Four ADP-ribosyltransferase (ADPRT) sequence types, and a myosin-cross-reactive antigen (MCRA) protein were discovered; we hypothesize that they are involved in modulation of host responses. The presence of polymorphisms among mouse SFB genomes suggests the evolution of distinct SFB lineages. Overall, our results reveal several aspects of SFB adaptation to the mammalian intestinal tract. PMID:22434425

  11. Trace Fossil Evidence of Trematode-Bivalve Parasite-Host Interactions in Deep Time.

    PubMed

    Huntley, John Warren; De Baets, Kenneth

    2015-01-01

    Parasitism is one of the most pervasive phenomena amongst modern eukaryotic life and yet, relative to other biotic interactions, almost nothing is known about its history in deep time. Digenean trematodes (Platyhelminthes) are complex life cycle parasites, which have practically no body fossil record, but induce the growth of characteristic malformations in the shells of their bivalve hosts. These malformations are readily preserved in the fossil record, but, until recently, have largely been overlooked by students of the fossil record. In this review, we present the various malformations induced by trematodes in bivalves, evaluate their distribution through deep time in the phylogenetic and ecological contexts of their bivalve hosts and explore how various taphonomic processes have likely biased our understanding of trematodes in deep time. Trematodes are known to negatively affect their bivalve hosts in a number of ways including castration, modifying growth rates, causing immobilization and, in some cases, altering host behaviour making the host more susceptible to their own predators. Digeneans are expected to be significant agents of natural selection. To that end, we discuss how bivalves may have adapted to their parasites via heterochrony and suggest a practical methodology for testing such hypotheses in deep time.

  12. Global Transcriptional Analysis of Virus-Host Interactions between Phage ϕ29 and Bacillus subtilis

    PubMed Central

    2016-01-01

    ABSTRACT The study of phage-host relationships is essential to understanding the dynamic of microbial systems. Here, we analyze genome-wide interactions of Bacillus subtilis and its lytic phage ϕ29 during the early stage of infection. Simultaneous high-resolution analysis of virus and host transcriptomes by deep RNA sequencing allowed us to identify differentially expressed bacterial genes. Phage ϕ29 induces significant transcriptional changes in about 0.9% (38/4,242) and 1.8% (76/4,242) of the host protein-coding genes after 8 and 16 min of infection, respectively. Gene ontology enrichment analysis clustered upregulated genes into several functional categories, such as nucleic acid metabolism (including DNA replication) and protein metabolism (including translation). Surprisingly, most of the transcriptional repressed genes were involved in the utilization of specific carbon sources such as ribose and inositol, and many contained promoter binding-sites for the catabolite control protein A (CcpA). Another interesting finding is the presence of previously uncharacterized antisense transcripts complementary to the well-known phage ϕ29 messenger RNAs that adds an additional layer to the viral transcriptome complexity. IMPORTANCE The specific virus-host interactions that allow phages to redirect cellular machineries and energy resources to support the viral progeny production are poorly understood. This study provides, for the first time, an insight into the genome-wide transcriptional response of the Gram-positive model Bacillus subtilis to phage ϕ29 infection. PMID:27489274

  13. High-throughput approaches to unravel hepatitis C virus-host interactions.

    PubMed

    Colpitts, Che C; El-Saghire, Hussein; Pochet, Nathalie; Schuster, Catherine; Baumert, Thomas F

    2016-06-15

    Hepatitis C virus (HCV) remains a major global health burden, with more than 130 million individuals chronically infected and at risk for the development of hepatocellular carcinoma (HCC). The recent clinical licensing of direct-acting antivirals enables viral cure. However, limited access to therapy and treatment failure in patient subgroups warrants a continuing effort to develop complementary antiviral strategies. Furthermore, once fibrosis is established, curing HCV infection does not eliminate the risk for HCC. High-throughput approaches and screens have enabled the investigation of virus-host interactions on a genome-wide scale. Gain- and loss-of-function screens have identified essential host-dependency factors in the HCV viral life cycle, such as host cell entry factors or regulatory factors for viral replication and assembly. Network analyses of systems-scale data sets provided a comprehensive view of the cellular state following HCV infection, thus improving our understanding of the virus-induced responses of the target cell. Interactome, metabolomics and gene expression studies identified dysregulated cellular processes potentially contributing to HCV pathogenesis and HCC. Drug screens using chemical libraries led to the discovery of novel antivirals. Here, we review the contribution of high-throughput approaches for the investigation of virus-host interactions, viral pathogenesis and drug discovery.

  14. Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model

    PubMed Central

    Tezera, Liku B; Bielecka, Magdalena K; Chancellor, Andrew; Reichmann, Michaela T; Shammari, Basim Al; Brace, Patience; Batty, Alex; Tocheva, Annie; Jogai, Sanjay; Marshall, Ben G; Tebruegge, Marc; Jayasinghe, Suwan N; Mansour, Salah; Elkington, Paul T

    2017-01-01

    Cell biology differs between traditional cell culture and 3-dimensional (3-D) systems, and is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection and is characterised by a spatially organised immune response and extracellular matrix remodelling. We developed a 3-D system incorporating virulent mycobacteria, primary human blood mononuclear cells and collagen–alginate matrix to dissect the host-pathogen interaction. Infection in 3-D led to greater cellular survival and permitted longitudinal analysis over 21 days. Key features of human tuberculosis develop, and extracellular matrix integrity favours the host over the pathogen. We optimised multiparameter readouts to study emerging therapeutic interventions: cytokine supplementation, host-directed therapy and immunoaugmentation. Each intervention modulates the host-pathogen interaction, but has both beneficial and harmful effects. This methodology has wide applicability to investigate infectious, inflammatory and neoplastic diseases and develop novel drug regimes and vaccination approaches. DOI: http://dx.doi.org/10.7554/eLife.21283.001 PMID:28063256

  15. A role for host-parasite interactions in the horizontal transfer of transposons across phyla.

    PubMed

    Gilbert, Clément; Schaack, Sarah; Pace, John K; Brindley, Paul J; Feschotte, Cédric

    2010-04-29

    Horizontal transfer (HT), or the passage of genetic material between non-mating species, is increasingly recognized as an important force in the evolution of eukaryotic genomes. Transposons, with their inherent ability to mobilize and amplify within genomes, may be especially prone to HT. However, the means by which transposons can spread across widely diverged species remain elusive. Here we present evidence that host-parasite interactions have promoted the HT of four transposon families between invertebrates and vertebrates. We found that Rhodnius prolixus, a triatomine bug feeding on the blood of various tetrapods and vector of Chagas' disease in humans, carries in its genome four distinct transposon families that also invaded the genomes of a diverse, but overlapping, set of tetrapods. The bug transposons are approximately 98% identical and cluster phylogenetically with those of the opossum and squirrel monkey, two of its preferred mammalian hosts in South America. We also identified one of these transposon families in the pond snail Lymnaea stagnalis, a cosmopolitan vector of trematodes infecting diverse vertebrates, whose ancestral sequence is nearly identical and clusters with those found in Old World mammals. Together these data provide evidence for a previously hypothesized role of host-parasite interactions in facilitating HT among animals. Furthermore, the large amount of DNA generated by the amplification of the horizontally transferred transposons supports the idea that the exchange of genetic material between hosts and parasites influences their genomic evolution.

  16. Enhanced understanding of the host-pathogen interaction in sepsis: new opportunities for omic approaches.

    PubMed

    Goh, Cyndi; Knight, Julian C

    2017-03-01

    Progress in sepsis research has been severely hampered by a heterogeneous disease phenotype, limiting the interpretation of clinical trials and the development of effective therapeutic interventions. Application of omics-based methodologies is advancing understanding of the dysregulated host immune response to infection in sepsis. However, the frequently elusive nature of the infecting organism in sepsis has limited efforts to understand the effect of disease heterogeneity involving the pathogen. Recent advances in nucleic acid sequencing-based pathogen analysis provide the opportunity for more accurate and comprehensive microbiological diagnosis. In this Review, we explore how better understanding of the host-pathogen interaction can substantially enhance, and in turn benefit from, current and future application of omics-based approaches to understand the host response in sepsis. We illustrate this using recent work accounting for heterogeneity involving the pathogen. We propose that there is a timely opportunity to further resolve sepsis heterogeneity by considering host-pathogen interactions, enabling progress towards a precision medicine approach.

  17. Automated image analysis of the host-pathogen interaction between phagocytes and Aspergillus fumigatus.

    PubMed

    Mech, Franziska; Thywissen, Andreas; Guthke, Reinhard; Brakhage, Axel A; Figge, Marc Thilo

    2011-05-05

    Aspergillus fumigatus is a ubiquitous airborne fungus and opportunistic human pathogen. In immunocompromised hosts, the fungus can cause life-threatening diseases like invasive pulmonary aspergillosis. Since the incidence of fungal systemic infections drastically increased over the last years, it is a major goal to investigate the pathobiology of A. fumigatus and in particular the interactions of A. fumigatus conidia with immune cells. Many of these studies include the activity of immune effector cells, in particular of macrophages, when they are confronted with conidia of A. fumigus wild-type and mutant strains. Here, we report the development of an automated analysis of confocal laser scanning microscopy images from macrophages coincubated with different A. fumigatus strains. At present, microscopy images are often analysed manually, including cell counting and determination of interrelations between cells, which is very time consuming and error-prone. Automation of this process overcomes these disadvantages and standardises the analysis, which is a prerequisite for further systems biological studies including mathematical modeling of the infection process. For this purpose, the cells in our experimental setup were differentially stained and monitored by confocal laser scanning microscopy. To perform the image analysis in an automatic fashion, we developed a ruleset that is generally applicable to phagocytosis assays and in the present case was processed by the software Definiens Developer XD. As a result of a complete image analysis we obtained features such as size, shape, number of cells and cell-cell contacts. The analysis reported here, reveals that different mutants of A. fumigatus have a major influence on the ability of macrophages to adhere and to phagocytose the respective conidia. In particular, we observe that the phagocytosis ratio and the aggregation behaviour of pksP mutant compared to wild-type conidia are both significantly increased.

  18. Oxidative Stress in Fungi: Its Function in Signal Transduction, Interaction with Plant Hosts, and Lignocellulose Degradation

    PubMed Central

    Breitenbach, Michael; Weber, Manuela; Rinnerthaler, Mark; Karl, Thomas; Breitenbach-Koller, Lore

    2015-01-01

    In this review article, we want to present an overview of oxidative stress in fungal cells in relation to signal transduction, interaction of fungi with plant hosts, and lignocellulose degradation. We will discuss external oxidative stress which may occur through the interaction with other microorganisms or plant hosts as well as internally generated oxidative stress, which can for instance originate from NADPH oxidases or “leaky” mitochondria and may be modulated by the peroxiredoxin system or by protein disulfide isomerases thus contributing to redox signaling. Analyzing redox signaling in fungi with the tools of molecular genetics is presently only in its beginning. However, it is already clear that redox signaling in fungal cells often is linked to cell differentiation (like the formation of perithecia), virulence (in plant pathogens), hyphal growth and the successful passage through the stationary phase. PMID:25854186

  19. Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

    PubMed

    Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

    2015-06-01

    Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment.

  20. Database of host-pathogen and related species interactions, and their global distribution.

    PubMed

    Wardeh, Maya; Risley, Claire; McIntyre, Marie Kirsty; Setzkorn, Christian; Baylis, Matthew

    2015-01-01

    Interactions between species, particularly where one is likely to be a pathogen of the other, as well as the geographical distribution of species, have been systematically extracted from various web-based, free-access sources, and assembled with the accompanying evidence into a single database. The database attempts to answer questions such as what are all the pathogens of a host, and what are all the hosts of a pathogen, what are all the countries where a pathogen was found, and what are all the pathogens found in a country. Two datasets were extracted from the database, focussing on species interactions and species distribution, based on evidence published between 1950-2012. The quality of their evidence was checked and verified against well-known, alternative, datasets of pathogens infecting humans, domestic animals and wild mammals. The presented datasets provide a valuable resource for researchers of infectious diseases of humans and animals, including zoonoses.

  1. Database of host-pathogen and related species interactions, and their global distribution

    PubMed Central

    Wardeh, Maya; Risley, Claire; McIntyre, Marie Kirsty; Setzkorn, Christian; Baylis, Matthew

    2015-01-01

    Interactions between species, particularly where one is likely to be a pathogen of the other, as well as the geographical distribution of species, have been systematically extracted from various web-based, free-access sources, and assembled with the accompanying evidence into a single database. The database attempts to answer questions such as what are all the pathogens of a host, and what are all the hosts of a pathogen, what are all the countries where a pathogen was found, and what are all the pathogens found in a country. Two datasets were extracted from the database, focussing on species interactions and species distribution, based on evidence published between 1950–2012. The quality of their evidence was checked and verified against well-known, alternative, datasets of pathogens infecting humans, domestic animals and wild mammals. The presented datasets provide a valuable resource for researchers of infectious diseases of humans and animals, including zoonoses. PMID:26401317

  2. Let your enemy do the work: within-host interactions between two fungal parasites of leaf-cutting ants.

    PubMed

    Hughes, W O H; Boomsma, J J

    2004-02-07

    Within-host competition is an important factor in host-parasite relationships, yet most studies consider interactions involving only single parasite species. We investigated the interaction between a virulent obligate entomopathogenic fungus, Metarhizium anisopliae var. anisopliae, and a normally avirulent, opportunistic fungal pathogen, Aspergillus flavus, in their leaf-cutting ant host, Acromyrmex echinatior. Surprisingly, the latter normally out-competed the former in mixed infections and had enhanced fitness relative to when infecting in isolation. The result is most probably due to Metarhizium inhibiting the host's immune defences, which would otherwise normally prevent infections by Aspergillus. With the host defences negated by the virulent parasite, the avirulent parasite was then able to out-compete its competitor. This result is strikingly similar to that seen in immunocompromised vertebrate hosts and indicates that avirulent parasites may play a more important role in host life histories than is generally realized.

  3. Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine.

    PubMed

    Contreras, Alejandra V; Cocom-Chan, Benjamin; Hernandez-Montes, Georgina; Portillo-Bobadilla, Tobias; Resendis-Antonio, Osbaldo

    2016-01-01

    It has been experimentally shown that host-microbial interaction plays a major role in shaping the wellness or disease of the human body. Microorganisms coexisting in human tissues provide a variety of benefits that contribute to proper functional activity in the host through the modulation of fundamental processes such as signal transduction, immunity and metabolism. The unbalance of this microbial profile, or dysbiosis, has been correlated with the genesis and evolution of complex diseases such as cancer. Although this latter disease has been thoroughly studied using different high-throughput (HT) technologies, its heterogeneous nature makes its understanding and proper treatment in patients a remaining challenge in clinical settings. Notably, given the outstanding role of host-microbiome interactions, the ecological interactions with microorganisms have become a new significant aspect in the systems that can contribute to the diagnosis and potential treatment of solid cancers. As a part of expanding precision medicine in the area of cancer research, efforts aimed at effective treatments for various kinds of cancer based on the knowledge of genetics, biology of the disease and host-microbiome interactions might improve the prediction of disease risk and implement potential microbiota-directed therapeutics. In this review, we present the state of the art of sequencing and metabolome technologies, computational methods and schemes in systems biology that have addressed recent breakthroughs of uncovering relationships or associations between microorganisms and cancer. Together, microbiome studies extend the horizon of new personalized treatments against cancer from the perspective of precision medicine through a synergistic strategy integrating clinical knowledge, HT data, bioinformatics, and systems biology.

  4. Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine

    PubMed Central

    Contreras, Alejandra V.; Cocom-Chan, Benjamin; Hernandez-Montes, Georgina; Portillo-Bobadilla, Tobias; Resendis-Antonio, Osbaldo

    2016-01-01

    It has been experimentally shown that host-microbial interaction plays a major role in shaping the wellness or disease of the human body. Microorganisms coexisting in human tissues provide a variety of benefits that contribute to proper functional activity in the host through the modulation of fundamental processes such as signal transduction, immunity and metabolism. The unbalance of this microbial profile, or dysbiosis, has been correlated with the genesis and evolution of complex diseases such as cancer. Although this latter disease has been thoroughly studied using different high-throughput (HT) technologies, its heterogeneous nature makes its understanding and proper treatment in patients a remaining challenge in clinical settings. Notably, given the outstanding role of host-microbiome interactions, the ecological interactions with microorganisms have become a new significant aspect in the systems that can contribute to the diagnosis and potential treatment of solid cancers. As a part of expanding precision medicine in the area of cancer research, efforts aimed at effective treatments for various kinds of cancer based on the knowledge of genetics, biology of the disease and host-microbiome interactions might improve the prediction of disease risk and implement potential microbiota-directed therapeutics. In this review, we present the state of the art of sequencing and metabolome technologies, computational methods and schemes in systems biology that have addressed recent breakthroughs of uncovering relationships or associations between microorganisms and cancer. Together, microbiome studies extend the horizon of new personalized treatments against cancer from the perspective of precision medicine through a synergistic strategy integrating clinical knowledge, HT data, bioinformatics, and systems biology. PMID:28018236

  5. Computational prediction of secretion systems and secretomes of Brucella: identification of novel type IV effectors and their interaction with the host.

    PubMed

    Sankarasubramanian, Jagadesan; Vishnu, Udayakumar S; Dinakaran, Vasudevan; Sridhar, Jayavel; Gunasekaran, Paramasamy; Rajendhran, Jeyaprakash

    2016-01-01

    Brucella spp. are facultative intracellular pathogens that cause brucellosis in various mammals including humans. Brucella survive inside the host cells by forming vacuoles and subverting host defence systems. This study was aimed to predict the secretion systems and the secretomes of Brucella spp. from 39 complete genome sequences available in the databases. Furthermore, an attempt was made to identify the type IV secretion effectors and their interactions with host proteins. We predicted the secretion systems of Brucella by the KEGG pathway and SecReT4. Brucella secretomes and type IV effectors (T4SEs) were predicted through genome-wide screening using JVirGel and S4TE, respectively. Protein-protein interactions of Brucella T4SEs with their hosts were analyzed by HPIDB 2.0. Genes coding for Sec and Tat pathways of secretion and type I (T1SS), type IV (T4SS) and type V (T5SS) secretion systems were identified and they are conserved in all the species of Brucella. In addition to the well-known VirB operon coding for the type IV secretion system (T4SS), we have identified the presence of additional genes showing homology with T4SS of other organisms. On the whole, 10.26 to 14.94% of total proteomes were found to be either secreted (secretome) or membrane associated (membrane proteome). Approximately, 1.7 to 3.0% of total proteomes were identified as type IV secretion effectors (T4SEs). Prediction of protein-protein interactions showed 29 and 36 host-pathogen specific interactions between Bos taurus (cattle)-B. abortus and Ovis aries (sheep)-B. melitensis, respectively. Functional characterization of the predicted T4SEs and their interactions with their respective hosts may reveal the secrets of host specificity of Brucella.

  6. Computational and Functional Analysis of the Virus-Receptor Interface Reveals Host Range Trade-Offs in New World Arenaviruses

    PubMed Central

    Kerr, Scott A.; Jackson, Eleisha L.; Lungu, Oana I.; Meyer, Austin G.; Demogines, Ann; Ellington, Andrew D.; Georgiou, George

    2015-01-01

    ABSTRACT Animal viruses frequently cause zoonotic disease in humans. As these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. Here, we develop a combined computational and experimental approach to assess the compatibility of New World arenaviruses, endemic in rodents, with the host TfR1 entry receptors of different potential new host species. Using signatures of positive selection, we identify a small motif on rodent TfR1 that conveys species specificity to the entry of viruses into cells. However, we show that mutations in this region affect the entry of each arenavirus differently. For example, a human single nucleotide polymorphism (SNP) in this region, L212V, makes human TfR1 a weaker receptor for one arenavirus, Machupo virus, but a stronger receptor for two other arenaviruses, Junin and Sabia viruses. Collectively, these findings set the stage for potential evolutionary trade-offs, where natural selection for resistance to one virus may make humans or rodents susceptible to other arenavirus species. Given the complexity of this host-virus interplay, we propose a computational method to predict these interactions, based on homology modeling and computational docking of the virus-receptor protein-protein interaction. We demonstrate the utility of this model for Machupo virus, for which a suitable cocrystal structural template exists. Our model effectively predicts whether the TfR1 receptors of different species will be functional receptors for Machupo virus entry. Approaches such at this could provide a first step toward computationally predicting the “host jumping” potential of a virus into a new host species. IMPORTANCE We demonstrate how evolutionary trade-offs may exist in the dynamic evolutionary interplay between viruses and their hosts, where natural selection for resistance to one virus could make humans or rodents susceptible

  7. Bacterial discrimination by Dictyostelid amoebae reveals the complexity of ancient interspecies interactions

    PubMed Central

    Nasser, Waleed; Santhanam, Balaji; Miranda, Edward Roshan; Parikh, Anup; Juneja, Kavina; Rot, Gregor; Dinh, Chris; Chen, Rui; Zupan, Blaz; Shaulsky, Gad; Kuspa, Adam

    2014-01-01

    Background Amoebae and bacteria interact within predator/prey and host/pathogen relationships, but the general response of amoeba to bacteria is not well understood. The amoeba Dictyostelium discoideum feeds on, and is colonized by diverse bacterial species including Gram-positive [Gram(+)] and Gram-negative [Gram(−)] bacteria, two major groups of bacteria that differ in structure and macromolecular composition. Results Transcriptional profiling of D. discoideum revealed sets of genes whose expression is enriched in amoebae interacting with different species of bacteria, including sets that appear specific to amoebae interacting with Gram(+), or with Gram(−) bacteria. In a genetic screen utilizing the growth of mutant amoebae on a variety of bacteria as a phenotypic readout, we identified amoebal genes that are only required for growth on Gram(+) bacteria, including one that encodes the cell surface protein gp130, as well as several genes that are only required for growth on Gram(−) bacteria including one that encodes a putative lysozyme, AlyL. These genes are required for parts of the transcriptional response of wild-type amoebae, and this allowed their classification into potential response pathways. Conclusions We have defined genes that are critical for amoebal survival during feeding on Gram(+), or Gram(−), bacteria which we propose form part of a regulatory network that allows D. discoideum to elicit specific cellular responses to different species of bacteria in order to optimize survival. PMID:23664307

  8. Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata)

    PubMed Central

    Roger, Emmanuel; Grunau, Christoph; Pierce, Raymond J.; Hirai, Hirohisa; Gourbal, Benjamin; Galinier, Richard; Emans, Rémi; Cesari, Italo M.; Cosseau, Céline; Mitta, Guillaume

    2008-01-01

    Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism—a “controlled chaos”—based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on

  9. Novel insights into human respiratory syncytial virus-host factor interactions through integrated proteomics and transcriptomics analysis.

    PubMed

    Dapat, Clyde; Oshitani, Hitoshi

    2016-01-01

    The lack of vaccine and limited antiviral options against respiratory syncytial virus (RSV) highlights the need for novel therapeutic strategies. One alternative is to develop drugs that target host factors required for viral replication. Several microarray and proteomics studies had been published to identify possible host factors that are affected during RSV replication. In order to obtain a comprehensive understanding of RSV-host interaction, we integrated available proteome and transcriptome datasets and used it to construct a virus-host interaction network. Then, we interrogated the network to identify host factors that are targeted by the virus and we searched for drugs from the DrugBank database that interact with these host factors, which may have potential applications in repositioning for future treatment options of RSV infection.

  10. A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract

    PubMed Central

    Ferrando, Maria Laura; Schultsz, Constance

    2016-01-01

    ABSTRACT Streptococcus suis (SS) is a zoonotic pathogen that can cause systemic infection in pigs and humans. The ingestion of contaminated pig meat is a well-established risk factor for zoonotic S. suis disease. In our studies, we provide experimental evidence that S. suis is capable to translocate across the host gastro-intestinal tract (GIT) using in vivo and in vitro models. Hence, S. suis should be considered an emerging foodborne pathogen. In this addendum, we give an overview of the complex interactions between S. suis and host-intestinal mucosa which depends on the host origin, the serotype and genotype of S. suis, as well as the presence and expression of virulence factors involved in host-pathogen interaction. Finally, we propose a hypothetical model of S. suis interaction with the host-GIT taking in account differences in conditions between the porcine and human host. PMID:26900998

  11. Novel insights into human respiratory syncytial virus-host factor interactions through integrated proteomics and transcriptomics analysis

    PubMed Central

    Dapat, Clyde; Oshitani, Hitoshi

    2016-01-01

    ABSTRACT The lack of vaccine and limited antiviral options against respiratory syncytial virus (RSV) highlights the need for novel therapeutic strategies. One alternative is to develop drugs that target host factors required for viral replication. Several microarray and proteomics studies had been published to identify possible host factors that are affected during RSV replication. In order to obtain a comprehensive understanding of RSV-host interaction, we integrated available proteome and transcriptome datasets and used it to construct a virus-host interaction network. Then, we interrogated the network to identify host factors that are targeted by the virus and we searched for drugs from the DrugBank database that interact with these host factors, which may have potential applications in repositioning for future treatment options of RSV infection. PMID:26760927

  12. Comparative phosphoproteomics reveals components of host cell invasion and post-transcriptional regulation during Francisella infection

    SciTech Connect

    Nakayasu, Ernesto S.; Tempel, Rebecca; Cambronne, Xiaolu A.; Petyuk, Vladislav A.; Jones, Marcus B.; Gritsenko, Marina A.; Monroe, Matthew E.; Yang, Feng; Smith, Richard D.; Adkins, Joshua N.; Heffron, Fred

    2013-09-22

    Francisella tularensis is a facultative intracellular bacterium that causes the deadly disease tularemia. Most evidence suggests that Francisella is not well recognized by the innate immune system that normally leads to cytokine expression and cell death. In previous work, we identified new bacterial factors that were hyper-cytotoxic to macrophages. Four of the identified hyper-cytotoxic strains (lpcC, manB, manC and kdtA) had an impaired lipopolysaccharide (LPS) synthesis and produced an exposed lipid A lacking the O-antigen. These mutants were not only hyper-cytotoxic but also were phagocytosed at much higher rates compared to the wild type parent strain. To elucidate the cellular signaling underlying this enhanced phagocytosis and cell death, we performed a large-scale comparative phosphoproteomic analysis of cells infected with wild-type and delta-lpcC F. novicida. Our data suggest that not only actin but also intermediate filaments and microtubules are important for F. novicida entry into the host cells. In addition, we observed differential phosphorylation of tristetraprolin (TTP), a key component of the mRNA-degrading machinery that controls the expression of a variety of genes including many cytokines. Infection with the delta-lpcC mutant induced the hyper-phosphorylation and inhibition of TTP, leading to the production of cytokines such as IL-1beta and TNF-alpha which may kill the host cells by triggering apoptosis. Together, our data provide new insights for Francisella invasion and a post-transcriptional mechanism that prevents the expression of host immune response factors that controls infection by this pathogen.

  13. Laboratory Investigations Reveal that Harmonia axyridis (Coleoptera: Coccinellidae) Is a Poor Host for Dinocampus coccinellae (Hymenoptera: Braconidae) in Brazil.

    PubMed

    de Castro-Guedes, CamilaFediuk; de Almeida, LúciaMassutti

    2016-01-01

    Harmonia axyridis (Pallas, 1773) is an Asian coccinellid released in several places to act as a biological control agent of aphids. Dinocampus coccinellae (Schrank, 1802) is an endoparasite that uses more than 40 coccinellid species as hosts. Thus, the aim of this study was to investigate the interactions between D. coccinellae and H. axyridis and to determine the impact of the parasitoid on the establishment capacity of H. axyridis It was also investigate the influence of host on the development of D. coccinellae using other Coccinellidae species as hosts: Cycloneda sanguinea, (L., 1763) Cycloneda pulchella (Klug, 1829), Eriopis connexa (Germar, 1824), and Olla v-nigrum (Mulsant, 1866) In no-choice tests, pupa was the least attacked stage, and the fourth instar and adults the most attacked. In choice tests, the pupa was less attacked when combined with all the other stages, and the fourth instar and adults the most attacked. There was statistical difference only for fecundity, fertility, and number of eggs/day, with higher values found in the non-parasitized control group. Due to the low rate of parasitism it is believed that D. coccinellae has little impact on the populations of this coccinellid in Brazil. However, it is noteworthy that an increase in H. axyridis coverage areas can affect the populations of D. coccinellae, as in some places of occurrence, H. axyridis has become the predominant species of Coccinellidae. The result can be a decrease in populations of this species of parasitoid or its better adaptation to the new host.

  14. Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions.

    PubMed

    Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard; Linde, Jörg

    2016-02-08

    Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host-pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling.

  15. Recent insights into host-pathogen interaction in white spot syndrome virus infected penaeid shrimp.

    PubMed

    Shekhar, M S; Ponniah, A G

    2015-07-01

    Viral disease outbreaks are a major concern impeding the development of the shrimp aquaculture industry. The viral disease due to white spot syndrome virus (WSSV) observed in early 1990s still continues unabated affecting the shrimp farms and cause huge economic loss to the shrimp aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand viral pathogenesis and shrimp response to WSSV at the molecular level. Identification and molecular characterization of WSSV proteins and receptors may facilitate in designing and development of novel therapeutics and antiviral drugs that may inhibit viral replication. Investigations into host-pathogen interactions might give new insights to viral infectivity, tissue tropism and defence mechanism elicited in response to WSSV infection. However, due to the limited information on WSSV gene function and host immune response, the signalling pathways which are associated in shrimp pathogen interaction have also not been elucidated completely. In the present review, the focus is on those shrimp proteins and receptors that are potentially involved in virus infection or in the defence mechanism against WSSV. In addition, the major signalling pathways involved in the innate immune response and the role of apoptosis in host-pathogen interaction is discussed.

  16. The mycobiota: interactions between commensal fungi and the host immune system

    PubMed Central

    Underhill, David M.; Iliev, Iliyan D.

    2015-01-01

    The body is host to a wide variety of microbial communities from which the immune system needs to protect us and which are important for normal immune system development and maintenance of healthy tissues and physiological processes. Investigators have largely focused on the bacterial members of these communities, but an increasing number of studies underscore the presence of fungi as well that may be important for defining the communities and their interactions with immune cells. In this Review we discuss what is currently known about the makeup of fungal communities on the body and features of the immune system that are particularly important for interacting with fungi at these sites. PMID:24854590

  17. Viral cystatin evolution and three-dimensional structure modelling: A case of directional selection acting on a viral protein involved in a host-parasitoid interaction

    PubMed Central

    Serbielle, Céline; Chowdhury, Shafinaz; Pichon, Samuel; Dupas, Stéphane; Lesobre, Jérôme; Purisima, Enrico O; Drezen, Jean-Michel; Huguet, Elisabeth

    2008-01-01

    Background In pathogens, certain genes encoding proteins that directly interact with host defences coevolve with their host and are subject to positive selection. In the lepidopteran host-wasp parasitoid system, one of the most original strategies developed by the wasps to defeat host defences is the injection of a symbiotic polydnavirus at the same time as the wasp eggs. The virus is essential for wasp parasitism success since viral gene expression alters the immune system and development of the host. As a wasp mutualist symbiont, the virus is expected to exhibit a reduction in genome complexity and evolve under wasp phyletic constraints. However, as a lepidopteran host pathogenic symbiont, the virus is likely undergoing strong selective pressures for the acquisition of new functions by gene acquisition or duplication. To understand the constraints imposed by this particular system on virus evolution, we studied a polydnavirus gene family encoding cyteine protease inhibitors of the cystatin superfamily. Results We show that cystatins are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of Cotesia congregata bracovirus cystatin 1 provides a powerful framework to position positively selected residues and reveal that they are concentrated in the vicinity of actives sites which interact with cysteine proteases directly. In addition, phylogenetic analyses reveal two different cystatin forms which evolved under different selective constraints and are characterized by independent adaptive duplication events. Conclusion Positive selection acts to maintain cystatin gene duplications and induces directional divergence presumably to ensure the presence of efficient and adapted cystatin forms. Directional selection has acted on key cystatin active sites, suggesting that cystatins coevolve with their host target. We can strongly suggest that cystatins constitute major virulence

  18. High Precision Measurement of Isotope Effects on Noncovalent Host-Guest Interactions

    SciTech Connect

    Mugridge, Jeffrey S.; Bergman, Robert G.; Raymond, Kenneth N.

    2009-06-23

    Isotope effects (IEs) are a powerful tool for examining the reactivity of, and interactions between, molecules. Recently, secondary IEs have been used to probe the nature of noncovalent interactions between guest and host molecules in supramolecular systems. While these studies can provide valuable insight into the specific interactions governing guest recognition and binding properties, IEs on noncovalent interactions are often very small and difficult to measure precisely. The Perrin group has developed an NMR titration method capable of determining ratios of equilibrium constants with remarkable precision. They have used this technique to study small, secondary equilibrium isotope effects (EIEs) on the acidity of carboxylic acids and phenols and on the basicity of amines, measuring differences down to thousandths of a pK{sub a} unit. It occurred to us that this titration method can in principle measure relative equilibrium constants for any process which is fast on the NMR timescale and for which the species under comparison are distinguishable by NMR. Here we report the application of this method to measure very small EIEs on noncovalent host-guest interactions in a supramolecular system.

  19. Ancient DNA from Coral-Hosted Symbiodinium Reveal a Static Mutualism over the Last 172 Years

    PubMed Central

    Baker, David M.; Weigt, Lee; Fogel, Marilyn; Knowlton, Nancy

    2013-01-01

    Ancient DNA (aDNA) provides powerful evidence for detecting the genetic basis for adaptation to environmental change in many taxa. Among the greatest of changes in our biosphere within the last century is rapid anthropogenic ocean warming. This phenomenon threatens corals with extinction, evidenced by the increasing observation of widespread mortality following mass bleaching events. There is some evidence and conjecture that coral-dinoflagellate symbioses change partnerships in response to changing external conditions over ecological and evolutionary timescales. Until now, we have been unable to ascertain the genetic identity of Symbiodinium hosted by corals prior to the rapid global change of the last century. Here, we show that Symbiodinium cells recovered from dry, century old specimens of 6 host species of octocorals contain sufficient DNA for amplification of the ITS2 subregion of the nuclear ribosomal DNA, commonly used for genotyping within this genus. Through comparisons with modern specimens sampled from similar locales we show that symbiotic associations among several species have been static over the last century, thereby suggesting that adaptive shifts to novel symbiont types is not common among these gorgonians, and perhaps, symbiotic corals in general. PMID:23405111

  20. Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries

    PubMed Central

    Toro-Ascuy, Daniela; Rojas-Araya, Bárbara; Valiente-Echeverría, Fernando; Soto-Rifo, Ricardo

    2016-01-01

    The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation. During its journey, the HIV-1 unspliced mRNA assembles into highly specific messenger ribonucleoproteins (mRNPs) containing many different host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay pathways such as up-frameshift suppressor 1 homolog (UPF1), Staufen double-stranded RNA binding protein 1/2 (STAU1/2), or components of miRNA-induced silencing complex (miRISC) and processing bodies (PBs). More recently, the HIV-1 unspliced mRNA was shown to contain N6-methyladenosine (m6A), allowing the recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), an m6A reader host protein involved in mRNA decay. Interestingly, these host proteins involved in mRNA decay were shown to play positive roles in viral gene expression and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication. This review summarizes the state of the art in terms of the interactions between HIV-1 unspliced mRNA and components of different host mRNA decay machineries. PMID:27886048

  1. Adding Biotic Interactions into Paleodistribution Models: A Host-Cleptoparasite Complex of Neotropical Orchid Bees

    PubMed Central

    Silva, Daniel Paiva; Varela, Sara; Nemésio, André; De Marco, Paulo

    2015-01-01

    Orchid bees compose an exclusive Neotropical pollinators group, with bright body coloration. Several of those species build their own nests, while others are reported as nest cleptoparasites. Here, the objective was to evaluate whether the inclusion of a strong biotic interaction, such as the presence of a host species, improved the ability of species distribution models (SDMs) to predict the geographic range of the cleptoparasite species. The target species were Aglae caerulea and its host species Eulaema nigrita. Additionally, since A. caerulea is more frequently found in the Amazon rather than the Cerrado areas, a secondary objective was to evaluate whether this species is increasing or decreasing its distribution given South American past and current climatic conditions. SDMs methods (Maxent and Bioclim), in addition with current and past South American climatic conditions, as well as the occurrences for A. caerulea and E. nigrita were used to generate the distribution models. The distribution of A. caerulea was generated with and without the inclusion of the distribution of E. nigrita as a predictor variable. The results indicate A. caerulea was barely affected by past climatic conditions and the populations from the Cerrado savanna could be at least 21,000 years old (the last glacial maximum), as well as the Amazonian ones. On the other hand, in this study, the inclusion of the host-cleptoparasite interaction complex did not statistically improve the quality of the produced models, which means that the geographic range of this cleptoparasite species is mainly constrained by climate and not by the presence of the host species. Nonetheless, this could also be caused by unknown complexes of other Euglossini hosts with A. caerulea, which still are still needed to be described by science. PMID:26069956

  2. The Drosophila melanogaster host model

    PubMed Central

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  3. Dwarf mistletoe-host interactions in mixed-conifer forests in the sierra nevada.

    PubMed

    Maloney, Patricia E; Rizzo, David M

    2002-06-01

    ABSTRACT We determined the spatial pattern of dwarf mistletoe (Arceuthobium spp.) associated with two different conifer hosts, white fir (Abies concolor) and Jeffrey pine (Pinus jeffreyi), in forests around the Lake Tahoe Basin and at the Teakettle Experimental Forest, both located in the Sierra Nevada. We also examined a number of host variables and bark beetle incidence to determine how these factors might be involved in the Arceuthobium-conifer interaction. There was no significant relationship between dwarf mistletoe-infected trees and associated bark beetles. We found the highest incidence of dwarf mistletoe on Jeffrey pine in Lake Tahoe (87%), followed by dwarf mistletoe on white fir in Lake Tahoe (30%), with the lowest incidence on white fir at Teakettle (27%). Dwarf mistletoe incidence on white fir in our Lake Tahoe grid was not correlated to density but the dwarf mistletoe rating (DMR) was positively correlated to host size. At the Teakettle Forest, dwarf mistletoe incidence on white fir was not correlated with host density but the DMR was correlated with host size. Dwarf mistletoe incidence and DMR on Jeffrey pine were correlated with host density. Individuals, of both conifer species, in all diameter size classes were susceptible to dwarf mistletoe, with the lowest infection rate in the seedling-10-cm-diameter class. Arceuthobium on white fir in Lake Tahoe showed spatial dependence to a range of 20 m. However, Arceuthobium on Jeffrey pine in Lake Tahoe and on white fir at Teakettle showed no clear pattern of spatial structuring. The degree of infection and stand history appear to be important in the spatial dynamics of Arceuthobium spp.

  4. Proteomic Analysis of Virus-Host Interactions in an Infectious Context Using Recombinant Viruses*

    PubMed Central

    Komarova, Anastassia V.; Combredet, Chantal; Meyniel-Schicklin, Laurène; Chapelle, Manuel; Caignard, Grégory; Camadro, Jean-Michel; Lotteau, Vincent; Vidalain, Pierre-Olivier; Tangy, Frédéric

    2011-01-01

    RNA viruses exhibit small-sized genomes encoding few proteins, but still establish complex networks of interactions with host cell components to achieve replication and spreading. Ideally, these virus-host protein interactions should be mapped directly in infected cell culture, but such a high standard is often difficult to reach when using conventional approaches. We thus developed a new strategy based on recombinant viruses expressing tagged viral proteins to capture both direct and indirect physical binding partners during infection. As a proof of concept, we engineered a recombinant measles virus (MV) expressing one of its virulence factors, the MV-V protein, with a One-STrEP amino-terminal tag. This allowed virus-host protein complex analysis directly from infected cells by combining modified tandem affinity chromatography and mass spectrometry analysis. Using this approach, we established a prosperous list of 245 cellular proteins interacting either directly or indirectly with MV-V, and including four of the nine already known partners of this viral factor. These interactions were highly specific of MV-V because they were not recovered when the nucleoprotein MV-N, instead of MV-V, was tagged. Besides key components of the antiviral response, cellular proteins from mitochondria, ribosomes, endoplasmic reticulum, protein phosphatase 2A, and histone deacetylase complex were identified for the first time as prominent targets of MV-V and the critical role of the later protein family in MV replication was addressed. Most interestingly, MV-V showed some preferential attachment to essential proteins in the human interactome network, as assessed by centrality and interconnectivity measures. Furthermore, the list of MV-V interactors also showed a massive enrichment for well-known targets of other viruses. Altogether, this clearly supports our approach based on reverse genetics of viruses combined with high-throughput proteomics to probe the interaction network that

  5. Population Structure of Phytophthora nicotianae Reveals Host-Specific Lineages on Brinjal, Ridge Gourd, and Tomato in South India.

    PubMed

    Chowdappa, P; Kumar, B J Nirmal; Kumar, S P Mohan; Madhura, S; Bhargavi, B Reddi; Lakshmi, M Jyothi

    2016-12-01

    Severe outbreaks of Phytophthora fruit rot on brinjal, ridge gourd, and tomato have been observed since 2011 in Andhra Pradesh, Karnataka, Telangana, and Tamil Nadu states of India. Therefore, 76 Phytophthora nicotianae isolates, recovered from brinjal (17), ridge gourd (40), and tomato (19) from different localities in these states during the June to December cropping season of 2012 and 2013, were characterized based on phenotypic and genotypic analyses and aggressiveness on brinjal, tomato, and ridge gourd. All brinjal and ridge gourd isolates were A2, while tomato isolates were both A1 (13) and A2 (6). All isolates were metalaxyl sensitive. In addition, isolates were genotyped for three mitochondrial (ribosomal protein L5-small subunit ribosomal RNA [rpl5-rns], small subunit ribosomal RNA-cytochrome c oxidase subunit 2 [rns-cox2], and cox2+spacer) and three nuclear loci (hypothetical protein [hyp], scp-like extracellular protein [scp], and beta-tubulin [β-tub]). All regions were polymorphic but nuclear regions were more variable than mitochondrial regions. The network analysis of genotypes using the combined dataset of three nuclear regions revealed a host-specific association. However, the network generated using mitochondrial regions limited such host-specific groupings only to brinjal isolates. P. nicotianae isolates were highly aggressive and produced significantly (P ≤ 0.01) larger lesions on their respective host of origin than on other hosts. The results indicate significant genetic variation in the population of P. nicotianae, leading to identification of host-specific lineages responsible for severe outbreaks on brinjal, ridge gourd, and tomato.

  6. Systems biology analysis of Brucella infected Peyer's patch reveals rapid invasion with modest transient perturbations of the host transcriptome.

    PubMed

    Rossetti, Carlos A; Drake, Kenneth L; Siddavatam, Prasad; Lawhon, Sara D; Nunes, Jairo E S; Gull, Tamara; Khare, Sangeeta; Everts, Robin E; Lewin, Harris A; Adams, Leslie Garry

    2013-01-01

    Brucella melitensis causes the most severe and acute symptoms of all Brucella species in human beings and infects hosts primarily through the oral route. The epithelium covering domed villi of jejunal-ileal Peyer's patches is an important site of entry for several pathogens, including Brucella. Here, we use the calf ligated ileal loop model to study temporal in vivo Brucella-infected host molecular and morphological responses. Our results document Brucella bacteremia occurring within 30 min after intraluminal inoculation of the ileum without histopathologic traces of lesions. Based on a system biology Dynamic Bayesian Network modeling approach (DBN) of microarray data, a very early transient perturbation of the host enteric transcriptome was associated with the initial host response to Brucella contact that is rapidly averted allowing invasion and dissemination. A detailed analysis revealed active expression of Syndecan 2, Integrin alpha L and Integrin beta 2 genes, which may favor initial Brucella adhesion. Also, two intestinal barrier-related pathways (Tight Junction and Trefoil Factors Initiated Mucosal Healing) were significantly repressed in the early stage of infection, suggesting subversion of mucosal epithelial barrier function to facilitate Brucella transepithelial migration. Simultaneously, the strong activation of the innate immune response pathways would suggest that the host mounts an appropriate protective immune response; however, the expression of the two key genes that encode innate immunity anti-Brucella cytokines such as TNF-α and IL12p40 were not significantly changed throughout the study. Furthermore, the defective expression of Toll-Like Receptor Signaling pathways may partially explain the lack of proinflammatory cytokine production and consequently the absence of morphologically detectable inflammation at the site of infection. Cumulatively, our results indicate that the in vivo pathogenesis of the early infectious process of Brucella is

  7. Dual RNA-Sequencing of Eucalyptus nitens during Phytophthora cinnamomi Challenge Reveals Pathogen and Host Factors Influencing Compatibility

    PubMed Central

    Meyer, Febé E.; Shuey, Louise S.; Naidoo, Sitha; Mamni, Thandekile; Berger, Dave K.; Myburg, Alexander A.; van den Berg, Noëlani; Naidoo, Sanushka

    2016-01-01

    Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers, and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1). Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR) genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets, and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction. PMID:26973660

  8. Insights into host-pathogen interactions from state-of-the-art animal models of respiratory Pseudomonas aeruginosa infections.

    PubMed

    Lorenz, Anne; Pawar, Vinay; Häussler, Susanne; Weiss, Siegfried

    2016-11-01

    Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies. Such knowledge might be accumulated in vitro. However, it is ultimately necessary to confirm these findings in vivo. In the present Review, we describe state-of-the-art in vivo models that allow studying P. aeruginosa infections in molecular detail. The portrayed mammalian models exclusively focus on respiratory infections. The data obtained by alternative animal models which lack lung tissue, often provide molecular insights that are easily transferable to mammals. Importantly, these surrogate in vivo systems reveal complex molecular interactions of P. aeruginosa with the host. Herein, we also provide a critical assessment of the advantages and disadvantages of such models.

  9. Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction

    PubMed Central

    Raghunathan, Anu; Reed, Jennifer; Shin, Sookil; Palsson, Bernhard; Daefler, Simon

    2009-01-01

    Background Infections with Salmonella cause significant morbidity and mortality worldwide. Replication of Salmonella typhimurium inside its host cell is a model system for studying the pathogenesis of intracellular bacterial infections. Genome-scale modeling of bacterial metabolic networks provides a powerful tool to identify and analyze pathways required for successful intracellular replication during host-pathogen interaction. Results We have developed and validated a genome-scale metabolic network of Salmonella typhimurium LT2 (iRR1083). This model accounts for 1,083 genes that encode proteins catalyzing 1,087 unique metabolic and transport reactions in the bacterium. We employed flux balance analysis and in silico gene essentiality analysis to investigate growth under a wide range of conditions that mimic in vitro and host cell environments. Gene expression profiling of S. typhimurium isolated from macrophage cell lines was used to constrain the model to predict metabolic pathways that are likely to be operational during infection. Conclusion Our analysis suggests that there is a robust minimal set of metabolic pathways that is required for successful replication of Salmonella inside the host cell. This model also serves as platform for the integration of high-throughput data. Its computational power allows identification of networked metabolic pathways and generation of hypotheses about metabolism during infection, which might be used for the rational design of novel antibiotics or vaccine strains. PMID:19356237

  10. Interaction of Chlamydia trachomatis serovar L2 with the host autophagic pathway.

    PubMed

    Al-Younes, Hesham M; Brinkmann, Volker; Meyer, Thomas F

    2004-08-01

    Chlamydiae are obligate intracellular pathogens that replicate within a membrane-bound compartment (the inclusion) and are associated with important human diseases, such as trachoma, pneumonia, and atherosclerosis. We have examined the interaction of the host autophagic pathway with Chlamydia trachomatis serovar L2 by using the specific autophagosomal stain monodansylcadaverine, antibodies to autophagosome-associated markers, and traditionally used autophagic inhibitors, particularly 3-methyladenine and amino acids. Chlamydial inclusions did not sequester monodansylcadaverine, suggesting absence of fusion with autophagosomes. Interestingly, exposure of cultures infected for 19 h to 3-methyladenine or single amino acids until the end of infection (44 h) caused various degrees of abnormalities in the inclusion maturation and in the progeny infectivity. Incubation of host cells with chemicals throughout the entire period of infection modulated the growth of Chlamydia even more dramatically. Remarkably, autophagosomal markers MAP-LC3 and calreticulin were redistributed to the inclusion of Chlamydia, a process that appears to be sensitive to 3-methyladenine and some amino acids. The present data indicate the lack of autophagosomal fusion with the inclusion because it was devoid of monodansylcadaverine and no distinct rim of autophagosomal protein-specific staining around the inclusion could be observed. However, high sensitivity of Chlamydia to conditions that could inhibit host autophagic pathway and the close association of MAP-LC3 and calreticulin with the inclusion membrane still suggest a potential role of host autophagy in the pathogenesis of Chlamydia.

  11. Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

    PubMed Central

    König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.

    2008-01-01

    Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154

  12. Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry

    PubMed Central

    Schäfer, Georgia; Blumenthal, Melissa J.; Katz, Arieh A.

    2015-01-01

    Currently, seven viruses, namely Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1), have been described to be consistently associated with different types of human cancer. These oncogenic viruses belong to distinct viral families, display diverse cell tropism and cause different malignancies. A key to their pathogenicity is attachment to the host cell and entry in order to replicate and complete their life cycle. Interaction with the host cell during viral entry is characterized by a sequence of events, involving viral envelope and/or capsid molecules as well as cellular entry factors that are critical in target cell recognition, thereby determining cell tropism. Most oncogenic viruses initially attach to cell surface heparan sulfate proteoglycans, followed by conformational change and transfer of the viral particle to secondary high-affinity cell- and virus-specific receptors. This review summarizes the current knowledge of the host cell surface factors and molecular mechanisms underlying oncogenic virus binding and uptake by their cognate host cell(s) with the aim to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection. PMID:26008702

  13. Interaction of human tumor viruses with host cell surface receptors and cell entry.

    PubMed

    Schäfer, Georgia; Blumenthal, Melissa J; Katz, Arieh A

    2015-05-22

    Currently, seven viruses, namely Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1), have been described to be consistently associated with different types of human cancer. These oncogenic viruses belong to distinct viral families, display diverse cell tropism and cause different malignancies. A key to their pathogenicity is attachment to the host cell and entry in order to replicate and complete their life cycle. Interaction with the host cell during viral entry is characterized by a sequence of events, involving viral envelope and/or capsid molecules as well as cellular entry factors that are critical in target cell recognition, thereby determining cell tropism. Most oncogenic viruses initially attach to cell surface heparan sulfate proteoglycans, followed by conformational change and transfer of the viral particle to secondary high-affinity cell- and virus-specific receptors. This review summarizes the current knowledge of the host cell surface factors and molecular mechanisms underlying oncogenic virus binding and uptake by their cognate host cell(s) with the aim to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection.

  14. "Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions"

    PubMed Central

    2012-01-01

    Background Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp. Results We show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (KD) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a KD of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG. Conclusions We believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro. PMID:22463075

  15. Rabies viruses leader RNA interacts with host Hsc70 and inhibits virus replication.

    PubMed

    Zhang, Ran; Liu, Chuangang; Cao, Yunzi; Jamal, Muhammad; Chen, Xi; Zheng, Jinfang; Li, Liang; You, Jing; Zhu, Qi; Liu, Shiyong; Dai, Jinxia; Cui, Min; Fu, Zhen F; Cao, Gang

    2017-03-23

    Viruses have been shown to be equipped with regulatory RNAs to evade host defense system. It has long been known that rabies virus (RABV) transcribes a small regulatory RNA, leader RNA (leRNA), which mediates the transition from viral RNA transcription to replication. However, the detailed molecular mechanism remains enigmatic. In the present study, we determined the genetic architecture of RABV leRNA and demonstrated its inhibitory effect on replication of wild-type rabies, DRV-AH08. The RNA immunoprecipitation results suggest that leRNA inhibits RABV replication via interfering the binding of RABV nucleoprotein with genomic RNA. Furthermore, we identified heat shock cognate 70 kDa protein (Hsc70) as a leRNA host cellular interacting protein, of which the expression level was dynamically regulated by RABV infection. Notably, our data suggest that Hsc70 was involved in suppressing RABV replication by leader RNA. Finally, our experiments imply that leRNA might be potentially useful as a novel drug in rabies post-exposure prophylaxis. Together, this study suggested leRNA in concert with its host interacting protein Hsc70, dynamically down-regulate RABV replication.

  16. What Do We Know about How Hantaviruses Interact with Their Different Hosts?

    PubMed Central

    Ermonval, Myriam; Baychelier, Florence; Tordo, Noël

    2016-01-01

    Hantaviruses, like other members of the Bunyaviridae family, are emerging viruses that are able to cause hemorrhagic fevers. Occasional transmission to humans is due to inhalation of contaminated aerosolized excreta from infected rodents. Hantaviruses are asymptomatic in their rodent or insectivore natural hosts with which they have co-evolved for millions of years. In contrast, hantaviruses cause different pathologies in humans with varying mortality rates, depending on the hantavirus species and its geographic origin. Cases of hemorrhagic fever with renal syndrome (HFRS) have been reported in Europe and Asia, while hantavirus cardiopulmonary syndromes (HCPS) are observed in the Americas. In some cases, diseases caused by Old World hantaviruses exhibit HCPS-like symptoms. Although the etiologic agents of HFRS were identified in the early 1980s, the way hantaviruses interact with their different hosts still remains elusive. What are the entry receptors? How do hantaviruses propagate in the organism and how do they cope with the immune system? This review summarizes recent data documenting interactions established by pathogenic and nonpathogenic hantaviruses with their natural or human hosts that could highlight their different outcomes. PMID:27529272

  17. Mathematical and computational approaches can complement experimental studies of host-pathogen interactions.

    PubMed

    Kirschner, Denise E; Linderman, Jennifer J

    2009-04-01

    In addition to traditional and novel experimental approaches to study host-pathogen interactions, mathematical and computer modelling have recently been applied to address open questions in this area. These modelling tools not only offer an additional avenue for exploring disease dynamics at multiple biological scales, but also complement and extend knowledge gained via experimental tools. In this review, we outline four examples where modelling has complemented current experimental techniques in a way that can or has already pushed our knowledge of host-pathogen dynamics forward. Two of the modelling approaches presented go hand in hand with articles in this issue exploring fluorescence resonance energy transfer and two-photon intravital microscopy. Two others explore virtual or 'in silico' deletion and depletion as well as a new method to understand and guide studies in genetic epidemiology. In each of these examples, the complementary nature of modelling and experiment is discussed. We further note that multi-scale modelling may allow us to integrate information across length (molecular, cellular, tissue, organism, population) and time (e.g. seconds to lifetimes). In sum, when combined, these compatible approaches offer new opportunities for understanding host-pathogen interactions.

  18. Impact of external forces on cyanophage-host interactions in aquatic ecosystems.

    PubMed

    Jassim, Sabah A A; Limoges, Richard G

    2013-10-01

    Cyanobacterial (algal) blooms have by convention been attributed to the excessive level of nutrients from pollution and runoff, which promotes the rapid growth and multiplication of cyanobacteria or algae. The cyanophage (virus) is the natural predator of cyanobacteria (the host). The aim of this review is to unveil certain pressures that disrupt cyanophage-host interactions and the formation of cyanobacterial blooms. This review focuses principally on the impact of greenhouse gases, ozone depletion, solar ultraviolet radiation (SUR) and the role of recently discovered virophages, which coexist with and in turn are the natural predator of phages. The key findings are that the increase in SUR, the mutation of cyanophages and cyanobacteria, along with changing nutrient levels, have combined with virophages to impede cyanophage-host interactions and the resultant viral infection and killing of the cyanobacterial cell, which is a necessary step in controlling cyanobacterial blooms. Consider this a 'call to action' for researchers interested in corrective action aimed at evolving aquatic ecosystems.

  19. Mathematical and computational approaches can complement experimental studies of host-pathogen interactions

    PubMed Central

    Kirschner, Denise E.; Linderman, Jennifer J.

    2009-01-01

    SUMMARY In addition to traditional and novel experimental approaches to study host-pathogen interactions, mathematical and computer modeling has recently been applied to address open questions in this area. These modeling tools not only offer an additional avenue for exploring disease dynamics at multiple biological scales, but also complement and extend knowledge gained via experimental tools. In this review, we outline four examples where modeling has complemented current experimental techniques in a way that can or has already pushed our knowledge of host-pathogen dynamics forward. Two of the modeling approaches presented go hand-in-hand with articles in this issue exploring FRET and two-photon intra-vital microscopy. Two others explore virtual or “in silico” deletion and depletion as well as a new method to understand and guide studies in genetic epidemiology. In each of these examples, the complementary nature of modeling and experiment is discussed. We further note that multi-scale modeling may allow us to integrate information across length (molecular, cellular, tissue, organism, population) and time (e.g. seconds to lifetimes). In sum, when combined, these compatible approaches offer new opportunities for understanding host-pathogen interactions. PMID:19134115

  20. What is a pathogen? Toward a process view of host-parasite interactions

    PubMed Central

    Méthot, Pierre-Olivier; Alizon, Samuel

    2014-01-01

    Until quite recently and since the late 19th century, medical microbiology has been based on the assumption that some micro-organisms are pathogens and others are not. This binary view is now strongly criticized and is even becoming untenable. We first provide a historical overview of the changing nature of host-parasite interactions, in which we argue that large-scale sequencing not only shows that identifying the roots of pathogenesis is much more complicated than previously thought, but also forces us to reconsider what a pathogen is. To address the challenge of defining a pathogen in post-genomic science, we present and discuss recent results that embrace the microbial genetic diversity (both within- and between-host) and underline the relevance of microbial ecology and evolution. By analyzing and extending earlier work on the concept of pathogen, we propose pathogenicity (or virulence) should be viewed as a dynamical feature of an interaction between a host and microbes. PMID:25483864

  1. Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction.

    PubMed

    Alcazar, Wilmer; López, Adrian Silva; Alakurtti, Sami; Tuononen, Maija-Liisa; Yli-Kauhaluoma, Jari; Ponte-Sucre, Alicia

    2014-11-01

    Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50% or IC50, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 μM; (2) compound 26 inhibits parasite growth with an IC50 lower than 1 μM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host-parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite-host cell interaction, as well as being leishmanicidal.

  2. Microbiota-mitochondria inter-talk: consequence for microbiota-host interaction.

    PubMed

    Saint-Georges-Chaumet, Yann; Edeas, Marvin

    2016-02-01

    New discoveries in metagenomics and clinical research have highlighted the importance of the gut microbiota for human health through the regulation of the host immune response and energetic metabolism. The microbiota interacts with host cells in particular by intermingling with the mitochondrial activities. This mitochondria-microbiota cross-talk is intriguing because mitochondria share many common structural and functional features with the prokaryotic world. Several studies reported a correlation between microbiota quality and diversity and mitochondrial function. The mitochondrial production of reactive oxygen species (ROS) plays an important role during the innate immune response and inflammation, and is often targeted by pathogenic bacteria. Data suggest that excessive mitochondrial ROS production may affect ROS signaling induced by the microbiota to regulate the gut epithelial barrier. Finally, the microbiota releases metabolites that can directly interfere with the mitochondrial respiratory chain and ATP production. Short chain fatty acids have beneficial effects on mitochondrial activity. All these data suggest that the microbiota targets mitochondria to regulate its interaction with the host. Imbalance of this targeting may result in a pathogenic state as observed in numerous studies. The challenge to find new treatments will be to find strategies to modulate the quality and diversity of the microbiota rather than acting on microbiota metabolites and microbiota-related factors.

  3. Pathogenesis and immunobiology of brucellosis: review of Brucella-host interactions.

    PubMed

    de Figueiredo, Paul; Ficht, Thomas A; Rice-Ficht, Allison; Rossetti, Carlos A; Adams, L Garry

    2015-06-01

    This review of Brucella-host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics.

  4. Babesia divergens and Neospora caninum apical membrane antigen 1 structures reveal selectivity and plasticity in apicomplexan parasite host cell invasion

    PubMed Central

    Tonkin, Michelle L; Crawford, Joanna; Lebrun, Maryse L; Boulanger, Martin J

    2013-01-01

    Host cell invasion by the obligate intracellular apicomplexan parasites, including Plasmodium (malaria) and Toxoplasma (toxoplasmosis), requires a step-wise mechanism unique among known host–pathogen interactions. A key step is the formation of the moving junction (MJ) complex, a circumferential constriction between the apical tip of the parasite and the host cell membrane that traverses in a posterior direction to enclose the parasite in a protective vacuole essential for intracellular survival. The leading model of MJ assembly proposes that Rhoptry Neck Protein 2 (RON2) is secreted into the host cell and integrated into the membrane where it serves as the receptor for apical membrane antigen 1 (AMA1) on the parasite surface. We have previously demonstrated that the AMA1-RON2 interaction is an effective target for inhibiting apicomplexan invasion. To better understand the AMA1-dependant molecular recognition events that promote invasion, including the significant AMA1-RON2 interaction, we present the structural characterization of AMA1 from the apicomplexan parasites Babesia divergens (BdAMA1) and Neospora caninum (NcAMA1) by X-ray crystallography. These studies offer intriguing structural insight into the RON2-binding surface groove in the AMA1 apical domain, which shows clear evidence for receptor–ligand co-evolution, and the hyper variability of the membrane proximal domain, which in Plasmodium is responsible for direct binding to erythrocytes. By incorporating the structural analysis of BdAMA1 and NcAMA1 with existing AMA1 structures and complexes we were able to define conserved pockets in the AMA1 apical groove that could be targeted for the design of broadly reactive therapeutics. PMID:23169033

  5. Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs.

    PubMed

    Qin, Yao; Zheng, Shijun J

    2017-01-14

    Infectious bursal disease (IBD) is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV). The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus-cell interactions during IBDV infection at the protein level.

  6. Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs

    PubMed Central

    Qin, Yao; Zheng, Shijun J.

    2017-01-01

    Infectious bursal disease (IBD) is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV). The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level. PMID:28098808

  7. Cohabitation in the Intestine: Interactions among Helminth Parasites, Bacterial Microbiota, and Host Immunity.

    PubMed

    Reynolds, Lisa A; Finlay, B Brett; Maizels, Rick M

    2015-11-01

    Both intestinal helminth parasites and certain bacterial microbiota species have been credited with strong immunomodulatory effects. Recent studies reported that the presence of helminth infection alters the composition of the bacterial intestinal microbiota and, conversely, that the presence and composition of the bacterial microbiota affect helminth colonization and persistence within mammalian hosts. This article reviews recent findings on these reciprocal relationships, in both human populations and mouse models, at the level of potential mechanistic pathways and the implications these bear for immunomodulatory effects on allergic and autoimmune disorders. Understanding the multidirectional complex interactions among intestinal microbes, helminth parasites, and the host immune system allows for a more holistic approach when using probiotics, prebiotics, synbiotics, antibiotics, and anthelmintics, as well as when designing treatments for autoimmune and allergic conditions.

  8. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes.

    PubMed

    Musso, Giovanni; Gambino, Roberto; Cassader, Maurizio

    2011-01-01

    Novel, culture-independent, molecular and metagenomic techniques have provided new insight into the complex interactions between the mammalian host and gut microbial species. It is increasingly evident that gut microbes may shape the host metabolic and immune network activity and ultimately influence the development of obesity and diabetes. We discuss the evidence connecting gut microflora to obesity and to type 1 and type 2 diabetes, and we present recent insights into potential mechanisms underlying this relationship: increased nutrient absorption from the diet, prolonged intestinal transit time, altered bile acid entero-hepatic cycle, increased cellular uptake of circulating triglycerides, enhanced de novo lipogenesis, reduced free fatty acid oxidation, altered tissue composition of biologically active polyunsaturated fatty acid, chronic low-grade inflammation triggered by the endotoxin toll-like receptor 4 axis, and altered intestinal barrier function.

  9. HIV Interaction With Human Host: HIV-2 As a Model of a Less Virulent Infection.

    PubMed

    Azevedo-Pereira, José Miguel; Santos-Costa, Quirina

    2016-01-01

    HIV-1 and HIV-2 are the causal agents of AIDS. While similar in many ways, a significant amount of data suggests that HIV-2 is less virulent than HIV-1. In fact, HIV-2 infection is characterized by a longer asymptomatic stage and lower transmission rate, and the majority of HIV-2-infected patients can be classified as long-term non-progressors or elite controllers. The mechanisms underlying the ability of human host to naturally control HIV-2 infection are far from being completely understood. The identification of the differences between HIV-1 and HIV-2 interactions with human host cells could provide important insights into several aspects of retroviral pathogenesis that remain elusive, with significant implications for HIV vaccine development and therapy. In this review, we delve into some of the differences that notably distinguish HIV-2 from HIV-1, highlighting possible consequences in the pathogenesis and natural history of both infections.

  10. Microbial Glycan Microarrays Define Key Features of Host-Microbial Interactions

    PubMed Central

    Stowell, Sean R.; Arthur, Connie M.; McBride, Ryan; Berger, Oren; Razi, Nahid; Heimburg-Molinaro, Jamie; Rodrigues, Lilian C.; Gourdine, Jean-Philippe; Noll, Alexander J.; von Gunten, Stephan; Smith, David F.; Knirel, Yuriy A.; Paulson, James C.; Cummings, Richard D.

    2014-01-01

    Genomic approaches continue to provide unprecedented insight into the microbiome, yet host immune interactions with diverse microbiota can be difficult to study. We therefore generated a microbial microarray containing defined antigens isolated from a broad range of microbial flora to examine adaptive and innate immunity. Serological studies with this microarray show that immunoglobulins from multiple mammalian species exhibit unique patterns of reactivity, while exposure of animals to distinct microbes induces specific serological recognition. While adaptive immunity exhibited plasticity toward microbial antigens, immunological tolerance limits reactivity toward self. We discovered that several innate immune galectins exhibit specific recognition of microbes that express self-like antigens, leading to direct killing of a broad range of gram negative and positive microbes. Thus, host protection against microbes appears to represent a balance between adaptive and innate immunity to defend against evolving antigenic determinants while protecting against molecular mimicry. PMID:24814672

  11. Interaction of streptococcal plasminogen binding proteins with the host fibrinolytic system.

    PubMed

    Fulde, Marcus; Steinert, Michael; Bergmann, Simone

    2013-01-01

    The ability to take advantage of plasminogen and its activated form plasmin is a common mechanism used by commensal as well as pathogenic bacteria in interaction with their respective host. Hence, a huge variety of plasminogen binding proteins and activation mechanisms exist. This review solely focuses on the genus Streptococcus and, in particular, on the so-called non-activating plasminogen binding proteins. Based on structural and functional differences, as well as on their mode of surface linkaging, three groups can be assigned: M-(like) proteins, surface displayed cytoplasmatic proteins with enzymatic activities ("moonlighting proteins") and other surface proteins. Here, the plasminogen binding sites and the interaction mechanisms are compared. Recent findings on the functional consequences of these interactions on tissue degradation and immune evasion are summarized.

  12. Interaction of streptococcal plasminogen binding proteins with the host fibrinolytic system

    PubMed Central

    Fulde, Marcus; Steinert, Michael; Bergmann, Simone

    2013-01-01

    The ability to take advantage of plasminogen and its activated form plasmin is a common mechanism used by commensal as well as pathogenic bacteria in interaction with their respective host. Hence, a huge variety of plasminogen binding proteins and activation mechanisms exist. This review solely focuses on the genus Streptococcus and, in particular, on the so-called non-activating plasminogen binding proteins. Based on structural and functional differences, as well as on their mode of surface linkaging, three groups can be assigned: M-(like) proteins, surface displayed cytoplasmatic proteins with enzymatic activities (“moonlighting proteins”) and other surface proteins. Here, the plasminogen binding sites and the interaction mechanisms are compared. Recent findings on the functional consequences of these interactions on tissue degradation and immune evasion are summarized. PMID:24319673

  13. Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

    PubMed Central

    David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

    2015-01-01

    Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

  14. Hepatitis C virus 3'UTR regulates viral translation through direct interactions with the host translation machinery.

    PubMed

    Bai, Yun; Zhou, Kaihong; Doudna, Jennifer A

    2013-09-01

    The 3' untranslated region (3'UTR) of hepatitis C virus (HCV) messenger RNA stimulates viral translation by an undetermined mechanism. We identified a high affinity interaction, conserved among different HCV genotypes, between the HCV 3'UTR and the host ribosome. The 3'UTR interacts with 40S ribosomal subunit proteins residing primarily in a localized region on the 40S solvent-accessible surface near the messenger RNA entry and exit sites. This region partially overlaps with the site where the HCV internal ribosome entry site was found to bind, with the internal ribosome entry site-40S subunit interaction being dominant. Despite its ability to bind to 40S subunits independently, the HCV 3'UTR only stimulates translation in cis, without affecting the first round translation rate. These observations support a model in which the HCV 3'UTR retains ribosome complexes during translation termination to facilitate efficient initiation of subsequent rounds of translation.

  15. Genome Scale Evolution of Myxoma Virus Reveals Host-Pathogen Adaptation and Rapid Geographic Spread

    PubMed Central

    Kerr, Peter J.; Rogers, Matthew B.; Fitch, Adam; DePasse, Jay V.; Cattadori, Isabella M.; Twaddle, Alan C.; Hudson, Peter J.; Tscharke, David C.; Read, Andrew F.; Holmes, Edward C.

    2013-01-01

    The evolutionary interplay between myxoma virus (MYXV) and the European rabbit (Oryctolagus cuniculus) following release of the virus in Australia in 1950 as a biological control is a classic example of host-pathogen coevolution. We present a detailed genomic and phylogeographic analysis of 30 strains of MYXV, including the Australian progenitor strain Standard Laboratory Strain (SLS), 24 Australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in Britain from 1954 and 1955. We show that in Australia MYXV has spread rapidly on a spatial scale, with multiple lineages cocirculating within individual localities, and that both highly virulent and attenuated viruses were still present in the field through the 1990s. In addition, the detection of closely related virus lineages at sites 1,000 km apart suggests that MYXV moves freely in geographic space, with mosquitoes, fleas, and rabbit migration all providing means of transport. Strikingly, despite multiple introductions, all modern viruses appear to be ultimately derived from the original introductions of SLS. The rapidity of MYXV evolution was also apparent at the genomic scale, with gene duplications documented in a number of viruses. Duplication of potential virulence genes may be important in increasing the expression of virulence proteins and provides the basis for the evolution of novel functions. Mutations leading to loss of open reading frames were surprisingly frequent and in some cases may explain attenuation, but no common mutations that correlated with virulence or attenuation were identified. PMID:24067966

  16. Genome scale evolution of myxoma virus reveals host-pathogen adaptation and rapid geographic spread.

    PubMed

    Kerr, Peter J; Rogers, Matthew B; Fitch, Adam; Depasse, Jay V; Cattadori, Isabella M; Twaddle, Alan C; Hudson, Peter J; Tscharke, David C; Read, Andrew F; Holmes, Edward C; Ghedin, Elodie

    2013-12-01

    The evolutionary interplay between myxoma virus (MYXV) and the European rabbit (Oryctolagus cuniculus) following release of the virus in Australia in 1950 as a biological control is a classic example of host-pathogen coevolution. We present a detailed genomic and phylogeographic analysis of 30 strains of MYXV, including the Australian progenitor strain Standard Laboratory Strain (SLS), 24 Australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in Britain from 1954 and 1955. We show that in Australia MYXV has spread rapidly on a spatial scale, with multiple lineages cocirculating within individual localities, and that both highly virulent and attenuated viruses were still present in the field through the 1990s. In addition, the detection of closely related virus lineages at sites 1,000 km apart suggests that MYXV moves freely in geographic space, with mosquitoes, fleas, and rabbit migration all providing means of transport. Strikingly, despite multiple introductions, all modern viruses appear to be ultimately derived from the original introductions of SLS. The rapidity of MYXV evolution was also apparent at the genomic scale, with gene duplications documented in a number of viruses. Duplication of potential virulence genes may be important in increasing the expression of virulence proteins and provides the basis for the evolution of novel functions. Mutations leading to loss of open reading frames were surprisingly frequent and in some cases may explain attenuation, but no common mutations that correlated with virulence or attenuation were identified.

  17. Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease

    PubMed Central

    Li, Wei; Liu, Liangyi; Gomez, Aurelie; Zhang, Jilu; Zhang, Qing; Choi, Sung W.; Greenson, Joel K.; Liu, Chen; Jiang, Di; Virts, Elizabeth; Kelich, Stephanie L.; Chu, Hong Wei; Flynn, Ryan; Blazar, Bruce R.; Hanenberg, Helmut; Hanash, Samir

    2016-01-01

    Gastrointestinal graft-versus-host-disease (GI-GVHD) is a life-threatening complication occurring after allogeneic hematopoietic cell transplantation (HCT), and a blood biomarker that permits stratification of HCT patients according to their risk of developing GI-GVHD would greatly aid treatment planning. Through in-depth, large-scale proteomic profiling of presymptomatic samples, we identified a T cell population expressing both CD146, a cell adhesion molecule, and CCR5, a chemokine receptor that is upregulated as early as 14 days after transplantation in patients who develop GI-GVHD. The CD4+CD146+CCR5+ T cell population is Th17 prone and increased by ICOS stimulation. shRNA knockdown of CD146 in T cells reduced their transmigration through endothelial cells, and maraviroc, a CCR5 inhibitor, reduced chemotaxis of the CD4+CD146+CCR5+ T cell population toward CCL14. Mice that received CD146 shRNA–transduced human T cells did not lose weight, showed better survival, and had fewer CD4+CD146+CCR5+ T cells and less pathogenic Th17 infiltration in the intestine, even compared with mice receiving maraviroc with control shRNA–transduced human T cells. Furthermore, the frequency of CD4+CD146+CCR5+ Tregs was increased in GI-GVHD patients, and these cells showed increased plasticity toward Th17 upon ICOS stimulation. Our findings can be applied to early risk stratification, as well as specific preventative therapeutic strategies following HCT. PMID:27195312

  18. Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants

    PubMed Central

    Greenwood, Edward JD; Matheson, Nicholas J; Wals, Kim; van den Boomen, Dick JH; Antrobus, Robin; Williamson, James C; Lehner, Paul J

    2016-01-01

    Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function. DOI: http://dx.doi.org/10.7554/eLife.18296.001 PMID:27690223

  19. Pathogenic landscapes: Interactions between land, people, disease vectors, and their animal hosts

    PubMed Central

    2010-01-01

    Background Landscape attributes influence spatial variations in disease risk or incidence. We present a review of the key findings from eight case studies that we conducted in Europe and West Africa on the impact of land changes on emerging or re-emerging vector-borne diseases and/or zoonoses. The case studies concern West Nile virus transmission in Senegal, tick-borne encephalitis incidence in Latvia, sandfly abundance in the French Pyrenees, Rift Valley Fever in the Ferlo (Senegal), West Nile Fever and the risk of malaria re-emergence in the Camargue, and rodent-borne Puumala hantavirus and Lyme borreliosis in Belgium. Results We identified general principles governing landscape epidemiology in these diverse disease systems and geographic regions. We formulated ten propositions that are related to landscape attributes, spatial patterns and habitat connectivity, pathways of pathogen transmission between vectors and hosts, scale issues, land use and ownership, and human behaviour associated with transmission cycles. Conclusions A static view of the "pathogenecity" of landscapes overlays maps of the spatial distribution of vectors and their habitats, animal hosts carrying specific pathogens and their habitat, and susceptible human hosts and their land use. A more dynamic view emphasizing the spatial and temporal interactions between these agents at multiple scales is more appropriate. We also highlight the complementarity of the modelling approaches used in our case studies. Integrated analyses at the landscape scale allows a better understanding of interactions between changes in ecosystems and climate, land use and human behaviour, and the ecology of vectors and animal hosts of infectious agents. PMID:20979609

  20. A review on computational systems biology of pathogen–host interactions

    PubMed Central

    Durmuş, Saliha; Çakır, Tunahan; Özgür, Arzucan; Guthke, Reinhard

    2015-01-01

    Pathogens manipulate the cellular mechanisms of host organisms via pathogen–host interactions (PHIs) in order to take advantage of the capabilities of host cells, leading to infections. The crucial role of these interspecies molecular interactions in initiating and sustaining infections necessitates a thorough understanding of the corresponding mechanisms. Unlike the traditional approach of considering the host or pathogen separately, a systems-level approach, considering the PHI system as a whole is indispensable to elucidate the mechanisms of infection. Following the technological advances in the post-genomic era, PHI data have been produced in large-scale within the last decade. Systems biology-based methods for the inference and analysis of PHI regulatory, metabolic, and protein–protein networks to shed light on infection mechanisms are gaining increasing demand thanks to the availability of omics data. The knowledge derived from the PHIs may largely contribute to the identification of new and more efficient therapeutics to prevent or cure infections. There are recent efforts for the detailed documentation of these experimentally verified PHI data through Web-based databases. Despite these advances in data archiving, there are still large amounts of PHI data in the biomedical literature yet to be discovered, and novel text mining methods are in development to unearth such hidden data. Here, we review a collection of recent studies on computational systems biology of PHIs with a special focus on the methods for the inference and analysis of PHI networks, covering also the Web-based databases and text-mining efforts to unravel the data hidden in the literature. PMID:25914674

  1. Genome-Wide Comparison of Magnaporthe Species Reveals a Host-Specific Pattern of Secretory Proteins and Transposable Elements

    PubMed Central

    Gowda, Malali

    2016-01-01

    Blast disease caused by the Magnaporthe species is a major factor affecting the productivity of rice, wheat and millets. This study was aimed at generating genomic information for rice and non-rice Magnaporthe isolates to understand the extent of genetic variation. We have sequenced the whole genome of the Magnaport