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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 genomics reveals distinct host-interacting traits of three major human-associated propionibacteria

    PubMed Central

    2013-01-01

    Background Propionibacteria are part of the human microbiota. Many studies have addressed the predominant colonizer of sebaceous follicles of the skin, Propionibacterium acnes, and investigated its association with the skin disorder acne vulgaris, and lately with prostate cancer. Much less is known about two other propionibacterial species frequently found on human tissue sites, Propionibacterium granulosum and Propionibacterium avidum. Here we analyzed two and three genomes of P. granulosum and P. avidum, respectively, and compared them to two genomes of P. acnes; we further highlight differences among the three cutaneous species with proteomic and microscopy approaches. Results Electron and atomic force microscopy revealed an exopolysaccharide (EPS)-like structure surrounding P. avidum cells, that is absent in P. acnes and P. granulosum. In contrast, P. granulosum possesses pili-like appendices, which was confirmed by surface proteome analysis. The corresponding genes were identified; they are clustered with genes encoding sortases. Both, P. granulosum and P. avidum lack surface or secreted proteins for predicted host-interacting factors of P. acnes, including several CAMP factors, sialidases, dermatan-sulphate adhesins, hyaluronidase and a SH3 domain-containing lipoprotein; accordingly, only P. acnes exhibits neuraminidase and hyaluronidase activities. These functions are encoded on previously unrecognized island-like regions in the genome of P. acnes. Conclusions Despite their omnipresence on human skin little is known about the role of cutaneous propionibacteria. All three species are associated with a variety of diseases, including postoperative and device-related abscesses and infections. We showed that the three organisms have evolved distinct features to interact with their human host. Whereas P. avidum and P. granulosum produce an EPS-like surface structure and pili-like appendices, respectively, P. acnes possesses a number of unique surface

  3. 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. PMID:26522078

  4. 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

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

    PubMed

    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

  6. 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

  7. In vitro adsorption revealing an apparent strong interaction between endophyte Pantoea agglomerans YS19 and host rice.

    PubMed

    Miao, Yuxuan; Zhou, Jia; Chen, Cuicui; Shen, Delong; Song, Wei; Feng, Yongjun

    2008-12-01

    Pantoea (formerly Enterobacter) agglomerans YS19 is a dominant diazotrophic endophyte isolated from rice (Oryza sativa cv. Yuefu) grown in a temperate-climate region in west Beijing, China. In vitro adsorption and invasion of YS19 on host plant root were studied in this research. Adsorption of YS19 on rice seedling roots closely resembled the Langmuir adsorption and showed a higher adsorption quantity than the control strains Paenibacillus polymyxa WY110 (a rhizospheric bacterium from the same rice cultivar) and Escherichia coli HB101 (a general model bacterium). Adsorption dynamics study revealed high rates and a long duration of the YS19-rice root adsorption process. Adsorption of YS19 was mainly observed on the root hair, though which it enters the plant. This in vitro adsorption study revealed an apparent strong interaction between YS19 and rice at the early endophyte-host recognition stage. PMID:18781359

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

    PubMed

    Tirosh, Osnat; Cohen, Yifat; 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

  9. 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

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

    PubMed

    Liu, Shufeng; Zhao, Ting; 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

  11. 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

  12. 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

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

    PubMed

    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

  14. Microsporidia-Host Interactions

    PubMed Central

    Szumowski, Suzannah C.; Troemel, Emily R.

    2015-01-01

    Microsporidia comprise one of the largest groups of obligate intracellular pathogens and can infect virtually all animals, but host response to these fungal-related microbes has been poorly understood. Several new studies of the host transcriptional response to microsporidia infection have found infection-induced regulation of genes involved in innate immunity, ubiquitylation, metabolism, and hormonal signaling. In addition, microsporidia have recently been shown to exploit host recycling endocytosis for exit from intestinal cells, and to interact with host degradation pathways. Microsporidia infection has also been shown to profoundly affect behavior in insect hosts. Altogether, these and other recent findings are providing much-needed insight into the underlying mechanisms of microsporidia interaction with host animals. PMID:25847674

  15. 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

  16. Exploring the associations of host genes for viral infection revealed by genome-wide RNAi and virus-host protein interactions.

    PubMed

    Xie, Dafei; Han, Lu; Luo, Yifu; Liu, Yang; He, Song; Bai, Hui; Wang, Shengqi; Bo, Xiaochen

    2015-09-01

    Genome-wide RNA interference screens have greatly facilitated the identification of essential host factors (EHFs) for viral infections, whose knockdown effects significantly influence virus replication but not host cell viability. However, little has been done to link EHFs with another important host factor type, i.e., virus targeting proteins (VTPs) that viruses directly interact with for intracellular survival, hampering the integrative understanding of virus-host interactions. Using EHFs and VTPs for human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV) infections, we found in general that despite limited overlap, EHFs and VTPs are both among the most differentially dysregulated genes in host transcriptional response to HIV and IAV infections, and notably they show consistency in regulation orientation. In the human protein-protein interaction network, both EHFs and VTPs hold topologically important positions at the global center, and importantly their direct interactions are statistically significant. We also identified BRCA1 and TP53 (or SMAD3 and PIK3R1) being the most extensive VTP-interacting EHFs (or EHF-interacting VTPs) for HIV-1 and IAV, which hold great potential in deciphering specific infection features and discovery of host directed antivirals. Further, most EHFs are the upstream regulators of VTPs when mapped in the same signaling pathways, some of which present intensive cross links. Collectively, these results provide insights into functional associations of the identified host gene factors for viral infections and highlight the regulatory significance of EHFs, and the necessity of their selective exploitation in confrontation to viral infections. PMID:26166390

  17. Mass spectrometric analysis reveals remnants of host-pathogen molecular interactions at the starch granule surface in wheat endosperm.

    PubMed

    Wall, Michael L; Wheeler, Heather L; Smith, Jeffrey; Figeys, Daniel; Altosaar, Illimar

    2010-09-01

    The starch granules of wheat seed are solar energy-driven deposits of fixed carbon and, as such, present themselves as targets of pathogen attack. The seed's array of antimicrobial proteins, peptides, and small molecules comprises a molecular defense against penetrating pathogens. In turn, pathogens exhibit an arsenal of enzymes to facilitate the degradation of the host's endosperm. In this context, the starch granule surface is a relatively unexplored domain in which unique molecular barriers may be deployed to defend against and inhibit the late stages of infection. Therefore, it was compelling to explore the starch granule surface in mature wheat seed, which revealed evidence of host-pathogen molecular interactions that may have occurred during grain development. In this study, starch granules from the soft wheat Triticum aestivum cv. AC Andrew and hard wheat T. turgidum durum were isolated and water washed 20 times, and their surface proteins were digested in situ with trypsin. The peptides liberated into the supernatant and the peptides remaining at the starch granule surface were separately examined. In this way, we demonstrated that the identified proteins have a strong affinity for the starch granule surface. Proteins with known antimicrobial activity were identified, as well as several proteins from the plant pathogens Agrobacterium tumefaciens, Pectobacterium carotovorum, Fusarium graminearum, Magnaporthe grisea, Xanthomonas axonopodis, and X. oryzae. Although most of these peptides corresponded to uncharacterized hypothetical proteins of fungal pathogens, several peptide fragments were identical to cytosolic and membrane proteins of specific microbial pathogens. During development and maturation, wheat seed appeared to have resisted infection and lysed the pathogens where, upon desiccation, the molecular evidence remained fixed at the starch granule surface. PMID:20701481

  18. Molecular characterization of S. japonicum exosome-like vesicles reveals their regulatory roles in parasite-host interactions.

    PubMed

    Zhu, Lihui; Liu, Juntao; Dao, Jinwei; Lu, Ke; Li, Hao; Gu, Huiming; Liu, Jinming; Feng, Xingang; Cheng, Guofeng

    2016-01-01

    Secreted extracellular vesicles play an important role in pathogen-host interactions. Increased knowledge of schistosome extracellular vesicles could provide insights into schistosome-host interactions and enable the development of novel intervention strategies to inhibit parasitic processes and lessen disease transmission. Here, we describe biochemical characterization of Schistosoma japonicum exosome-like vesicles (S. japonicum EVs). A total of 403 proteins were identified in S. japonicum EVs, and bioinformatics analyses indicated that these proteins were mainly involved in binding, catalytic activity, and translation regulatory activity. Next, we characterized the population of small RNAs associated with S. japonicum EVs. Further studies demonstrated that mammalian cells could internalize S. japonicum EVs and transfer their cargo miRNAs to recipient cells. Additionally, we found that a specific miRNA, likely originating from a final host, ocu-miR-191-5p, is also associated with S. japonicum EVs. Overall, our findings demonstrate that S. japonicum EVs could be implicated in the pathogenesis of schistosomiasis via a mechanism involving the transfer of their cargo miRNAs to hosts. Our findings provide novel insights into the mechanisms of schistosome-host interactions. PMID:27172881

  19. Molecular characterization of S. japonicum exosome-like vesicles reveals their regulatory roles in parasite-host interactions

    PubMed Central

    Zhu, Lihui; Liu, Juntao; Dao, Jinwei; Lu, Ke; Li, Hao; Gu, Huiming; Liu, Jinming; Feng, Xingang; Cheng, Guofeng

    2016-01-01

    Secreted extracellular vesicles play an important role in pathogen-host interactions. Increased knowledge of schistosome extracellular vesicles could provide insights into schistosome-host interactions and enable the development of novel intervention strategies to inhibit parasitic processes and lessen disease transmission. Here, we describe biochemical characterization of Schistosoma japonicum exosome-like vesicles (S. japonicum EVs). A total of 403 proteins were identified in S. japonicum EVs, and bioinformatics analyses indicated that these proteins were mainly involved in binding, catalytic activity, and translation regulatory activity. Next, we characterized the population of small RNAs associated with S. japonicum EVs. Further studies demonstrated that mammalian cells could internalize S. japonicum EVs and transfer their cargo miRNAs to recipient cells. Additionally, we found that a specific miRNA, likely originating from a final host, ocu-miR-191–5p, is also associated with S. japonicum EVs. Overall, our findings demonstrate that S. japonicum EVs could be implicated in the pathogenesis of schistosomiasis via a mechanism involving the transfer of their cargo miRNAs to hosts. Our findings provide novel insights into the mechanisms of schistosome-host interactions. PMID:27172881

  20. Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

    PubMed Central

    Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

    2015-01-01

    The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

  1. 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

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

    PubMed

    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

  3. An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions.

    PubMed

    Arvey, Aaron; Tempera, Italo; Tsai, Kevin; Chen, Horng-Shen; Tikhmyanova, Nadezhda; Klichinsky, Michael; Leslie, Christina; Lieberman, Paul M

    2012-08-16

    Epstein-Barr virus (EBV), which is associated with multiple human tumors, persists as a minichromosome in the nucleus of B lymphocytes and induces malignancies through incompletely understood mechanisms. Here, we present a large-scale functional genomic analysis of EBV. Our experimentally generated nucleosome positioning maps and viral protein binding data were integrated with over 700 publicly available high-throughput sequencing data sets for human lymphoblastoid cell lines mapped to the EBV genome. We found that viral lytic genes are coexpressed with cellular cancer-associated pathways, suggesting that the lytic cycle may play an unexpected role in virus-mediated oncogenesis. Host regulators of viral oncogene expression and chromosome structure were identified and validated, revealing a role for the B cell-specific protein Pax5 in viral gene regulation and the cohesin complex in regulating higher order chromatin structure. Our findings provide a deeper understanding of latent viral persistence in oncogenesis and establish a valuable viral genomics resource for future exploration. PMID:22901543

  4. Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals Regulators of the Type I Interferon Response.

    PubMed

    Wu, Jian; Cai, Baowei; Sun, Wenxiang; Huang, Ruili; Liu, Xueqiao; Lin, Meng; Pattaradilokrat, Sittiporn; Martin, Scott; Qi, Yanwei; Nair, Sethu C; Bolland, Silvia; Cohen, Jeffrey I; Austin, Christopher P; Long, Carole A; Myers, Timothy G; Wang, Rong-Fu; Su, Xin-Zhuan

    2015-07-28

    Invading pathogens trigger specific host responses, an understanding of which might identify genes that function in pathogen recognition and elimination. In this study, we performed trans-species expression quantitative trait locus (ts-eQTL) analysis using genotypes of the Plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. We significantly linked 1,054 host genes to parasite genetic loci (LOD score ≥ 3.0). Using LOD score patterns, which produced results that differed from direct expression-level clustering, we grouped host genes that function in related pathways, allowing functional prediction of unknown genes. As a proof of principle, 14 of 15 randomly selected genes predicted to function in type I interferon (IFN-I) responses were experimentally validated using overexpression, small hairpin RNA knockdown, viral infection, and/or infection of knockout mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways. PMID:26190101

  5. The complexity of signaling in host-pathogen interactions revealed by the Toxoplasma gondii-dependent modulation of JNK phosphorylation

    PubMed Central

    Carmen, John C.; Southard, R. Chase; Sinai, Anthony P.

    2009-01-01

    The inhibition of apoptosis by Toxoplasma gondii is governed by its modulation of several signaling cascades including the NFκappaB and JNK pathways. This is evident in the dysregulation of JNK activation following treatment with UV and TNFα, both apoptogenic stimuli. Infection-mediated interference with the JNK cascade was found to be highly reproducible in HeLa cells. In light of emerging evidence regarding cross talk between the JNK and NFκB cascades, we examined the impact of infection in wild type and RelA/p65−/− mouse embryonic fibroblasts (MEF). Remarkably, parasite infection failed to significantly impact both UV and TNFα-mediated JNK phosphorylation in both cell lines suggesting a cell type specific effect. Furthermore siRNA-mediated knockdown of RelA/p65 failed to impact the parasite mediated effects on stimulus dependent activation of JNK in HeLa cells. Finally, the infection mediated suppression of JNK phosphorylation in HeLa cells did not result in decreased JNK kinase activity. Rather, the reduced levels of phospho-JNK in infected cells correlated with increased phosphatase activity noted by the partial rescue of the phenotype following treatment with okadaic acid. Taken together the results indicate that manipulation of the JNK-pathway does not involve NFκB and is furthermore not a central component of the parasite enforced block of apoptosis. It further highlights the complexity of these systems and the danger of extrapolating results both within and across pathogen-host cell systems based on limited studies. PMID:18929560

  6. Global Gene Expression Analysis of the Zoonotic Parasite Trichinella spiralis Revealed Novel Genes in Host Parasite Interaction

    PubMed Central

    Jiang, Ning; Wang, Jielin; Tang, Bin; Lu, Huijun; Peng, Shuai; Chang, Zhiguang; Tang, Yizhi; Yin, Jigang; Liu, Mingyuan; Tan, Yan; Chen, Qijun

    2012-01-01

    Background Trichinellosis is a typical food-borne zoonotic disease which is epidemic worldwide and the nematode Trichinella spiralis is the main pathogen. The life cycle of T. spiralis contains three developmental stages, i.e. adult worms, new borne larva (new borne L1 larva) and muscular larva (infective L1 larva). Stage-specific gene expression in the parasites has been investigated with various immunological and cDNA cloning approaches, whereas the genome-wide transcriptome and expression features of the parasite have been largely unknown. The availability of the genome sequence information of T. spiralis has made it possible to deeply dissect parasite biology in association with global gene expression and pathogenesis. Methodology and Principal Findings In this study, we analyzed the global gene expression patterns in the three developmental stages of T. spiralis using digital gene expression (DGE) analysis. Almost 15 million sequence tags were generated with the Illumina RNA-seq technology, producing expression data for more than 9,000 genes, covering 65% of the genome. The transcriptome analysis revealed thousands of differentially expressed genes within the genome, and importantly, a panel of genes encoding functional proteins associated with parasite invasion and immuno-modulation were identified. More than 45% of the genes were found to be transcribed from both strands, indicating the importance of RNA-mediated gene regulation in the development of the parasite. Further, based on gene ontological analysis, over 3000 genes were functionally categorized and biological pathways in the three life cycle stage were elucidated. Conclusions and Significance The global transcriptome of T. spiralis in three developmental stages has been profiled, and most gene activity in the genome was found to be developmentally regulated. Many metabolic and biological pathways have been revealed. The findings of the differential expression of several protein families facilitate

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

    PubMed

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

    2016-06-01

    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

  8. Progress in computational studies of host-pathogen interactions.

    PubMed

    Zhou, Hufeng; Jin, Jingjing; Wong, Limsoon

    2013-04-01

    Host-pathogen interactions are important for understanding infection mechanism and developing better treatment and prevention of infectious diseases. Many computational studies on host-pathogen interactions have been published. Here, we review recent progress and results in this field and provide a systematic summary, comparison and discussion of computational studies on host-pathogen interactions, including prediction and analysis of host-pathogen protein-protein interactions; basic principles revealed from host-pathogen interactions; and database and software tools for host-pathogen interaction data collection, integration and analysis. PMID:23600809

  9. 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

  10. 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

  11. Deep sequencing of amplified Prasinovirus and host green algal genes from an Indian Ocean transect reveals interacting trophic dependencies and new genotypes.

    PubMed

    Clerissi, Camille; Desdevises, Yves; Romac, Sarah; Audic, Stéphane; de Vargas, Colomban; Acinas, Silvia G; Casotti, Raffaella; Poulain, Julie; Wincker, Patrick; Hingamp, Pascal; Ogata, Hiroyuki; Grimsley, Nigel

    2015-12-01

    High-throughput sequencing of Prasinovirus DNA polymerase and host green algal (Mamiellophyceae) ribosomal RNA genes was used to analyse the diversity and distribution of these taxa over a ∼10 000 km latitudinal section of the Indian Ocean. New viral and host groups were identified among the different trophic conditions observed, and highlighted that although unknown prasinoviruses are diverse, the cosmopolitan algal genera Bathycoccus, Micromonas and Ostreococcus represent a large proportion of the host diversity. While Prasinovirus communities were correlated to both the geography and the environment, host communities were not, perhaps because the genetic marker used lacked sufficient resolution. Nevertheless, analysis of single environmental variables showed that eutrophic conditions strongly influence the distributions of both hosts and viruses. Moreover, these communities were not correlated, in their composition or specific richness. These observations could result from antagonistic dynamics, such as that illustrated in a prey-predator model, and/or because hosts might be under a complex set of selective pressures. Both of these reasons must be considered to interpret environmental surveys of viruses and hosts, because covariation does not always imply interaction. PMID:26472079

  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. 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

  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

    2016-04-01

    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

  15. 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

  16. 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.

  17. Cytological and Transcriptional Dynamics Analysis of Host Plant Revealed Stage-Specific Biological Processes Related to Compatible Rice-Ustilaginoidea virens Interaction

    PubMed Central

    Chao, Jinquan; Jin, Jie; Wang, Dong; Han, Ran; Zhu, Renshan; Zhu, Yingguo; Li, Shaoqing

    2014-01-01

    Abstract Rice false smut, a fungal disease caused by Ustilaginoidea virens is becoming a severe detriment to rice production worldwide. However, little is known about the molecular response of rice to attacks by the smut pathogen. In this article, we define the initial infection process as having three stages: initial colonization on the pistil (stage 1, S1), amplification on the anther (stage 2, S2) and sporulation in the anther chambers (stage 3, S3). Based on the transcriptome of rice hosts in response to U. virens in two separate years, we identified 126, 204, and 580 specific regulated genes in their respective stages S1, S2, and S3, respectively, by excluding common expression patterns in other openly biotic/abiotic databases using bioinformatics. As the disease progresses, several stage-specific biological processes (BP) terms were distinctively enriched: “Phosphorylation” in stage S1, “PCD” in S2, and “Cell wall biogenesis” in S3, implying a concise signal cascade indicative of the tactics that smut pathogens use to control host rice cells during infection. 113 regulated genes were coexpressed among the three stages. They shared highly conserved promoter cis-element in the promoters in response to the regulation of WRKY and Myb for up-regulation, and ABA and Ca2+ for down regulation, indicating their potentially critical roles in signal transduction during rice-U. virens interaction. We further analyzed seven highly regulated unique genes; four were specific to pollen development, implying that pollen-related genes play critical roles in the establishment of rice susceptibility to U. virens. To my knowledge, this is the first report about probing of molecular response of rice to smut pathogen infection, which will greatly expand our understanding of the molecular events surrounding infection by rice false smut. PMID:24646527

  18. Polymicrobial-Host Interactions during Infection.

    PubMed

    Tay, Wei Hong; Chong, Kelvin Kian Long; Kline, Kimberly A

    2016-08-28

    Microbial pathogenesis research has, historically, focused on the study of infections as monomicrobial events. However, the advent of next generation sequencing and culture-independent identification methods has revealed that many, if not most, infections are polymicrobial either in origin or in manifestation. Polymicrobial infections are often associated with increased infection severity and poorer patient outcome. Multiple infecting microbes can interact synergistically to induce virulence traits, alter the infected niche, or modulate the host immune response, all of which can promote polymicrobial infection. Importantly, a polymicrobial environment at the time of inoculation, consisting of multiple pathogens or pathogens in combination with the native microbiota, can contribute to the pathogenic progression of a single predominant organism at the time of diagnosis. Hence, in order to completely understand and elucidate the impact of these polymicrobial interactions on infection outcomes, a thorough examination of the entire microbial community present throughout the pathogenic cascade is required: from the time of inoculation to symptomology to resolution. In this review, we highlight the themes of metabolite exploitation, immune modulation, niche optimization, and virulence induction that contribute to polymicrobial infections. We focus on recent literature about microbe-microbe and microbe-host interactions that promote polymicrobial infections with an emphasis on understanding these interactions to identify better interventions for these sometimes complex infections. PMID:27170548

  19. Recent insights into hepatitis B virus-host interactions.

    PubMed

    Ezzikouri, Sayeh; Ozawa, Makoto; Kohara, Michinori; Elmdaghri, Naima; Benjelloun, Soumaya; Tsukiyama-Kohara, Kyoko

    2014-06-01

    Hepatitis B virus (HBV) poses a threat to global public health mainly because of complications of HBV-related chronic liver disease. HBV exhibits a narrow host range, replicating primarily in hepatocytes by a still poorly understood mechanism. For the generation of progeny virions, HBV depends on interactions with specific host factors through its life cycle. Revealing and characterizing these interactions are keys to identifying novel antiviral targets, and to developing specific treatment strategies for HBV patients. In this review, recent insights into the HBV-host interactions, especially on virus entry, intracellular trafficking, genome transcription and replication, budding and release, and even cellular restriction factors were reviewed. PMID:24604126

  20. Coevolutionary interactions between host and parasite genotypes.

    PubMed

    Lambrechts, Louis; Fellous, Simon; Koella, Jacob C

    2006-01-01

    More than 20 years after Dawkins introduced the concept of "extended phenotype" (i.e. phenotypes of hosts and parasites result from interactions between the two genomes) and although this idea has now reached contemporary textbooks of evolutionary biology, most studies of the evolution of host-parasite systems still focus solely on either the host or the parasite, neglecting the role of the other partner. It is important to consider that host and parasite genotypes share control of the epidemiological parameters of their relationship. Moreover, not only the traits of the infection but also the genetic correlations among these and other traits that determine fitness might be controlled by interactions between host and parasite genotypes. PMID:16310412

  1. Host-Microbe Interactions in Caenorhabditis elegans

    PubMed Central

    Hou, Aixin

    2013-01-01

    A good understanding of how microbes interact with hosts has a direct bearing on our capability of fighting infectious microbial pathogens and making good use of beneficial ones. Among the model organisms used to study reciprocal actions among microbes and hosts, C. elegans may be the most advantageous in the context of its unique attributes such as the short life cycle, easiness of laboratory maintenance, and the availability of different genetic mutants. This review summarizes the recent advances in understanding host-microbe interactions in C. elegans. Although these investigations have greatly enhanced our understanding of C. elegans-microbe relationships, all but one of them involve only one or few microbial species. We argue here that more research is needed for exploring the evolution and establishment of a complex microbial community in the worm's intestine and its interaction with the host. PMID:23984180

  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. Host-Pathogen Interactions 1

    PubMed Central

    Cervone, Felice; Hahn, Michael G.; De Lorenzo, Giulia; Darvill, Alan; Albersheim, Peter

    1989-01-01

    This paper describes the effect of a plant-derived polygalacturonase-inhibiting protein (PGIP) on the activity of endopolygalacturonases isolated from fungi. PGIP's effect on endopolygalacturonases is to enhance the production of oligogalacturonides that are active as elicitors of phytoalexin (antibiotic) accumulation and other defense reactions in plants. Only oligogalacturonides with a degree of polymerization higher than nine are able to elicit phytoalexin synthesis in soybean cotyledons. In the absence of PGIP, a 1-minute exposure of polygalacturonic acid to endopolygalacturonase resulted in the production of elicitor-active oligogalacturonides. However, the enzyme depolymerized essentially all of the polygalacturonic acid substrate to elicitor-inactive oligogalacturonides within 15 minutes. When the digestion of polygalacturonic acid was carried out with the same amount of enzyme but in the presence of excess PGIP, the rate of production of elicitor-active oligogalacturonides was dramatically altered. The amount of elicitor-active oligogalacturonide steadily increased for 24 hours. It was only after about 48 hours that the enzyme converted the polygalacturonic acid into short, elicitor-inactive oligomers. PGIP is a specific, reversible, saturable, high-affinity receptor for endopolygalacturonase. Formation of the PGIP-endopolygalacturonase complex results in increased concentrations of oligogalacturonides that activate plant defense responses. The interaction of the plant-derived PGIP with fungal endopolygalacturonases may be a mechanism by which plants convert endopolygalacturonase, a factor important for the virulence of pathogens, into a factor that elicits plant defense mechanisms. PMID:16666805

  4. Glycoconjugates in Host-Helminth Interactions

    PubMed Central

    Prasanphanich, Nina Salinger; Mickum, Megan L.; Heimburg-Molinaro, Jamie; Cummings, Richard D.

    2013-01-01

    Helminths are multicellular parasitic worms that comprise a major class of human pathogens and cause an immense amount of suffering worldwide. Helminths possess an abundance of complex and unique glycoconjugates that interact with both the innate and adaptive arms of immunity in definitive and intermediate hosts. These glycoconjugates represent a major untapped reservoir of immunomodulatory compounds, which have the potential to treat autoimmune and inflammatory disorders, and antigenic glycans, which could be exploited as vaccines and diagnostics. This review will survey current knowledge of the interactions between helminth glycans and host immunity and highlight the gaps in our understanding which are relevant to advancing therapeutics, vaccine development, and diagnostics. PMID:24009607

  5. Comparative genome analysis of Burkholderia phytofirmans PsJN reveals a wide spectrum of endophytic lifestyles based on interaction strategies with host plants

    PubMed Central

    Mitter, Birgit; Petric, Alexandra; Shin, Maria W.; Chain, Patrick S. G.; Hauberg-Lotte, Lena; Reinhold-Hurek, Barbara; Nowak, Jerzy; Sessitsch, Angela

    2013-01-01

    Burkholderia phytofirmans PsJN is a naturally occurring plant-associated bacterial endophyte that effectively colonizes a wide range of plants and stimulates their growth and vitality. Here we analyze whole genomes, of PsJN and of eight other endophytic bacteria. This study illustrates that a wide spectrum of endophytic life styles exists. Although we postulate the existence of typical endophytic traits, no unique gene cluster could be exclusively linked to the endophytic lifestyle. Furthermore, our study revealed a high genetic diversity among bacterial endophytes as reflected in their genotypic and phenotypic features. B. phytofirmans PsJN is in many aspects outstanding among the selected endophytes. It has the biggest genome consisting of two chromosomes and one plasmid, well-equipped with genes for the degradation of complex organic compounds and detoxification, e.g., 24 glutathione-S-transferase (GST) genes. Furthermore, strain PsJN has a high number of cell surface signaling and secretion systems and harbors the 3-OH-PAME quorum-sensing system that coordinates the switch of free-living to the symbiotic lifestyle in the plant-pathogen R. solanacearum. The ability of B. phytofirmans PsJN to successfully colonize such a wide variety of plant species might be based on its large genome harboring a broad range of physiological functions. PMID:23641251

  6. Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions.

    PubMed

    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

  7. 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

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

    PubMed Central

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

    2015-01-01

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

  9. Host-Salmonella interaction: human trials.

    PubMed

    Levine, M M; Tacket, C O; Sztein, M B

    2001-01-01

    Human clinical trials, including experimental challenges of volunteers with pathogenic Salmonella enterica serovar Typhi, small phase I and II trials that monitor the immune responses to vaccines, and large-scale controlled field trials that assess vaccine efficacy under conditions of natural challenge, have helped elucidate the interactions between Salmonella typhi and human hosts. PMID:11755415

  10. 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...

  11. 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

  12. Interaction of spirochetes with the host.

    PubMed

    Hindersson, P; Thomas, D; Stamm, L; Penn, C; Norris, S; Joens, L A

    1992-01-01

    The success of an invading organism must depend on several cytoplasmic, surface-associated and secreted factors. The technical difficulties in handling pathogenic spirochetes like Treponema pallidum and Borrelia burgdorferi have made it difficult to define specific factors involved in entry and long-term survival. The problem of defining virulence factors has been attacked by several strategies: T. pallidum secretes a number of immunogenic low molecular mass proteins. The most predominant are of molecular weight 15.5 and 22 kDa. Preliminary data suggest that antibodies against these proteins induce protective immunity in rabbits experimentally infected with T. pallidum. Many potentially important surface-associated antigens of T. pallidum have now been cloned and characterized. Two of these, TpD and TpE, are lipoproteins which exhibit characteristic size heterogeneity. The apparent molecular weight of TpE from T. pallidum and T. pertenue are different. The clinical symptoms in syphilis and yaws are very different, but sequence analysis of TpE has shown that the TpE proteins are indeed very similar in the two strains. This observation makes it unlikely that heterogeneity of TpE can account for the different clinical symptoms of syphilis and yaws. Sequence data for another newly sequenced surface-associated antigen of T. pallidum (molecular weight 41 kDa) indicate that this protein is involved in glucose transport and chemotaxis/motility. Intracellular factors like the molecular chaperonin GroEL have been documented both in treponemes and borreliae. This stress protein is involved in cellular repair processes and folding/assembly of protein subunits. Indirect evidence suggests that GroEL affects the ability of spirochetes to survive in the stressful environment of the infected host. Several lines of evidence suggest that the Osp proteins of Borrelia are important for host/parasite interaction. Further support for this idea has come from studies of a series of

  13. Using metabolomics to dissect host-parasite interactions.

    PubMed

    Kloehn, J; Blume, M; Cobbold, S A; Saunders, E C; Dagley, M J; McConville, M J

    2016-08-01

    Protozoan parasites have evolved diverse growth and metabolic strategies for surviving and proliferating within different extracellular and intracellular niches in their mammalian hosts. Metabolomic approaches, including high coverage metabolite profiling and (13)C/(2)H-stable isotope labeling, are increasingly being used to identify parasite metabolic pathways that are important for survival and replication in vivo. These approaches are highlighting new links between parasite carbon metabolism and the ability of different parasite stages to colonize specific niches or host cell types. They have also revealed novel metabolic regulatory mechanisms that are important for homeostasis and survival in potentially nutrient variable environments. These studies highlight the importance of parasite and host metabolism as determinants of host-parasite interactions. PMID:27200489

  14. Host-pathogen interactions in bacterial meningitis.

    PubMed

    Doran, Kelly S; Fulde, Marcus; Gratz, Nina; Kim, Brandon J; Nau, Roland; Prasadarao, Nemani; Schubert-Unkmeir, Alexandra; Tuomanen, Elaine I; Valentin-Weigand, Peter

    2016-02-01

    Bacterial meningitis is a devastating disease occurring worldwide with up to half of the survivors left with permanent neurological sequelae. Due to intrinsic properties of the meningeal pathogens and the host responses they induce, infection can cause relatively specific lesions and clinical syndromes that result from interference with the function of the affected nervous system tissue. Pathogenesis is based on complex host-pathogen interactions, some of which are specific for certain bacteria, whereas others are shared among different pathogens. In this review, we summarize the recent progress made in understanding the molecular and cellular events involved in these interactions. We focus on selected major pathogens, Streptococcus pneumonia, S. agalactiae (Group B Streptococcus), Neisseria meningitidis, and Escherichia coli K1, and also include a neglected zoonotic pathogen, Streptococcus suis. These neuroinvasive pathogens represent common themes of host-pathogen interactions, such as colonization and invasion of mucosal barriers, survival in the blood stream, entry into the central nervous system by translocation of the blood-brain and blood-cerebrospinal fluid barrier, and induction of meningeal inflammation, affecting pia mater, the arachnoid and subarachnoid spaces. PMID:26744349

  15. Ehrlichia chaffeensis Exploits Host SUMOylation Pathways To Mediate Effector-Host Interactions and Promote Intracellular Survival

    PubMed Central

    Dunphy, Paige Selvy; Luo, Tian

    2014-01-01

    Ehrlichia chaffeensis is an obligately intracellular Gram-negative bacterium that selectively infects mononuclear phagocytes. We recently reported that E. chaffeensis utilizes a type 1 secretion (T1S) system to export tandem repeat protein (TRP) effectors and demonstrated that these effectors interact with a functionally diverse array of host proteins. By way of these interactions, TRP effectors modulate host cell functions; however, the molecular basis of these interactions and their roles in ehrlichial pathobiology are not well defined. In this study, we describe the first bacterial protein posttranslational modification (PTM) by the small ubiquitin-like modifier (SUMO). The E. chaffeensis T1S effector TRP120 is conjugated to SUMO at a carboxy-terminal canonical consensus SUMO conjugation motif in vitro and in human cells. In human cells, TRP120 was selectively conjugated with SUMO2/3 isoforms. Disruption of TRP120 SUMOylation perturbed interactions with known host proteins, through predicted SUMO interaction motif-dependent and -independent mechanisms. E. chaffeensis infection did not result in dramatic changes in the global host SUMOylated protein profile, but a robust colocalization of predominately SUMO1 with ehrlichial inclusions was observed. Inhibiting the SUMO pathway with a small-molecule inhibitor had a significant impact on E. chaffeensis replication and recruitment of the TRP120-interacting protein polycomb group ring finger protein 5 (PCGF5) to the inclusion, indicating that the SUMO pathway is critical for intracellular survival. This study reveals the novel exploitation of the SUMO pathway by Ehrlichia, which facilitates effector-eukaryote interactions necessary to usurp the host and create a permissive intracellular niche. PMID:25047847

  16. Use of host-like peptide motifs in viral proteins is a prevalent strategy in host-virus interactions

    PubMed Central

    Hagai, Tzachi; Azia, Ariel; Babu, M. Madan; Andino, Raul

    2014-01-01

    Virus interact extensively with host proteins, but the mechanisms controlling these interactions are not well understood. We present a comprehensive analysis of eukaryotic linear-peptide motifs (ELMs) in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we identify a large number of potentially functional ELMs and observe that the occurrence of ELMs is often evolutionarily conserved but not uniform across virus families. Some viral proteins contain multiple types of ELMs, in striking similarity to complex regulatory modules in host proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to diverse environments. PMID:24882001

  17. 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

  18. Helicobacter pylori: Genomic Insight into the Host-Pathogen Interaction

    PubMed Central

    Haley, Kathryn P.; Gaddy, Jennifer A.

    2015-01-01

    The advent of genomic analyses has revolutionized the study of human health. Infectious disease research in particular has experienced an explosion of bacterial genomic, transcriptomic, and proteomic data complementing the phenotypic methods employed in traditional bacteriology. Together, these techniques have revealed novel virulence determinants in numerous pathogens and have provided information for potential chemotherapeutics. The bacterial pathogen, Helicobacter pylori, has been recognized as a class 1 carcinogen and contributes to chronic inflammation within the gastric niche. Genomic analyses have uncovered remarkable coevolution between the human host and H. pylori. Perturbation of this coevolution results in dysregulation of the host-pathogen interaction, leading to oncogenic effects. This review discusses the relationship of H. pylori with the human host and environment and the contribution of each of these factors to disease progression, with an emphasis on features that have been illuminated by genomic tools. PMID:25722969

  19. 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

  20. HIV-host interactome revealed directly from infected cells.

    PubMed

    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:27572969

  1. Interaction of Mycobacterium tuberculosis with Host Cell Death Pathways

    PubMed Central

    Srinivasan, Lalitha; Ahlbrand, Sarah; Briken, Volker

    2014-01-01

    Mycobacterium tuberculosis (Mtb) has coevolved with humans for tens of thousands of years. It is thus highly adapted to its human host and has evolved multiple mechanisms to manipulate host immune responses to its advantage. One central host pathogen interaction modality is host cell death pathways. Host cell apoptosis is associated with a protective response to Mtb infection, whereas a necrotic response favors the pathogen. Consistently, Mtb inhibits host cell apoptosis signaling but promotes induction of programmed necrosis. The molecular mechanisms involved in Mtb-mediated host cell death manipulation, the consequences for host immunity, and the potential for therapeutic and preventive approaches will be discussed. PMID:24968864

  2. Epigenomic regulation of host-microbiota interactions

    PubMed Central

    Alenghat, Theresa; Artis, David

    2014-01-01

    The trillions of beneficial commensal microorganisms that normally reside in the gastrointestinal tract have emerged as a critical source of environmentally-derived stimuli that can impact health and disease. However, the underlying cellular and molecular mechanisms that recognize commensal bacteria-derived signals and regulate mammalian homeostasis are just beginning to be defined. Highly coordinated epigenomic modifications allow mammals to alter the transcriptional program of a cell in response to environmental cues. These modifications may play a key role in regulating the dynamic relationship between mammals and their microbiota. Here we review recent advances in understanding of the interplay between the microbiota and mammalian epigenomic pathways, and highlight emerging findings that implicate a central role for histone deacetylases (HDACs) in orchestrating host-microbiota interactions. PMID:25443494

  3. Pathogenesis of influenza: virus-host interactions.

    PubMed

    Godlee, Alexandra; Almond, Mark H; Dong, Tao

    2011-08-01

    Since their inception in March 1972, Keystone Symposia on Molecular and Cellular Biology have brought together scientists from across the globe to discuss key biological topics. Now in its 40th year, it is a completely independent, nonprofit organization devoted solely to providing outstanding scientific conferences in all areas of the biological and biomedical sciences. Towards the end of May 2011, over 200 virologists and immunologists came to Hong Kong, an appropriate setting given the emergence of H5N1, to discuss influenza virus and host interactions. The meeting, expertly organized by Siamon Gordon (University of Oxford, Oxofrd, UK), Malik Peiris (University of Hong Kong, Hong Kong, China) and Kanta Subbarao (NIAID, NIH, MD, USA), took place in the aftermath of the first pandemic in 40 years and provided great insight into both pandemic H1N1 and H5N1. This article focuses on some of the recurring themes that were discussed during the week. PMID:21819324

  4. Influenza virus binds its host cell using multiple dynamic interactions

    PubMed Central

    Sieben, Christian; Kappel, Christian; Zhu, Rong; Wozniak, Anna; Rankl, Christian; Hinterdorfer, Peter; Grubmüller, Helmut; Herrmann, Andreas

    2012-01-01

    Influenza virus belongs to a wide range of enveloped viruses. The major spike protein hemagglutinin binds sialic acid residues of glycoproteins and glycolipids with dissociation constants in the millimolar range [Sauter NK, et al. (1992) Biochemistry 31:9609–9621], indicating a multivalent binding mode. Here, we characterized the attachment of influenza virus to host cell receptors using three independent approaches. Optical tweezers and atomic force microscopy-based single-molecule force spectroscopy revealed very low interaction forces. Further, the observation of sequential unbinding events strongly suggests a multivalent binding mode between virus and cell membrane. Molecular dynamics simulations reveal a variety of unbinding pathways that indicate a highly dynamic interaction between HA and its receptor, allowing rationalization of influenza virus–cell binding quantitatively at the molecular level. PMID:22869709

  5. Enteroviral proteases: structure, host interactions and pathogenicity.

    PubMed

    Laitinen, Olli H; Svedin, Emma; Kapell, Sebastian; Nurminen, Anssi; Hytönen, Vesa P; Flodström-Tullberg, Malin

    2016-07-01

    Enteroviruses are common human pathogens, and infections are particularly frequent in children. Severe infections can lead to a variety of diseases, including poliomyelitis, aseptic meningitis, myocarditis and neonatal sepsis. Enterovirus infections have also been implicated in asthmatic exacerbations and type 1 diabetes. The large disease spectrum of the closely related enteroviruses may be partially, but not fully, explained by differences in tissue tropism. The molecular mechanisms by which enteroviruses cause disease are poorly understood, but there is increasing evidence that the two enteroviral proteases, 2A(pro) and 3C(pro) , are important mediators of pathology. These proteases perform the post-translational proteolytic processing of the viral polyprotein, but they also cleave several host-cell proteins in order to promote the production of new virus particles, as well as to evade the cellular antiviral immune responses. Enterovirus-associated processing of cellular proteins may also contribute to pathology, as elegantly demonstrated by the 2A(pro) -mediated cleavage of dystrophin in cardiomyocytes contributing to Coxsackievirus-induced cardiomyopathy. It is likely that improved tools to identify targets for these proteases will reveal additional host protein substrates that can be linked to specific enterovirus-associated diseases. Here, we discuss the function of the enteroviral proteases in the virus replication cycle and review the current knowledge regarding how these proteases modulate the infected cell in order to favour virus replication, including ways to avoid detection by the immune system. We also highlight new possibilities for the identification of protease-specific cellular targets and thereby a way to discover novel mechanisms contributing to disease. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27145174

  6. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25473880

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

    PubMed Central

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

    2015-01-01

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

  9. 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

  10. 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

  11. Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells.

    PubMed

    Day, Christopher J; Tran, Elizabeth N; Semchenko, Evgeny A; Tram, Greg; Hartley-Tassell, Lauren E; Ng, Preston S K; King, Rebecca M; Ulanovsky, Rachel; McAtamney, Sarah; Apicella, Michael A; Tiralongo, Joe; Morona, Renato; Korolik, Victoria; Jennings, Michael P

    2015-12-29

    Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-to-cell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede high-affinity protein-glycan or protein-protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high-affinity host-glycan:bacterial-glycan pairs with equilibrium dissociation constants (K(D)) ranging between 100 nM and 50 µM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems. PMID:26676578

  12. 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

  13. 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

  14. Versatile Supramolecular Gene Vector Based on Host-Guest Interaction.

    PubMed

    Liu, Jia; Hennink, Wim E; van Steenbergen, Mies J; Zhuo, Renxi; Jiang, Xulin

    2016-04-20

    It is a great challenge to arrange multiple functional components into one gene vector system to overcome the extra- and intracellular obstacles for gene therapy. In this study, we developed a supramolecular approach for constructing a versatile gene delivery system composed of adamantyl-terminated functional polymers and a β-cyclodextrin based polymer. Adamantyl-functionalized low molecular weight PEIs (PEI-Ad) and PEG (Ad-PEG) as well as poly(β-cyclodextrin) (PCD) were synthesized by one-step chemical reactions. The supramolecular inclusion complex formed from PCD to assemble LMW PEI-Ad4 via host-guest interactions can condense plasmid DNA to form nanopolyplexes by electrostatic interactions. The supramolecular polyplexes can be further PEGylated with Ad-PEG to form inclusion complexes, which showed increased salt and serum stability. In vitro experiments revealed that these supramolecular assembly polyplexes had good cytocompatibility and showed high transfection activity close to that of the commercial ExGen 500 at high dose of DNA. Also, the supramolecular vector system exhibited about 60% silencing efficiency as a siRNA vector. Thus, a versatile effective supramolecular gene vector based on host-guest complexes was fabricated with good cytocompatbility and transfection activity. PMID:27019340

  15. 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...

  16. Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells

    PubMed Central

    Day, Christopher J.; Tran, Elizabeth N.; Semchenko, Evgeny A.; Tram, Greg; Hartley-Tassell, Lauren E.; Ng, Preston S. K.; King, Rebecca M.; Ulanovsky, Rachel; McAtamney, Sarah; Apicella, Michael A.; Tiralongo, Joe; Morona, Renato; Korolik, Victoria; Jennings, Michael P.

    2015-01-01

    Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-to-cell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede high-affinity protein–glycan or protein–protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high-affinity host–glycan:bacterial–glycan pairs with equilibrium dissociation constants (KD) ranging between 100 nM and 50 µM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems. PMID:26676578

  17. 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

  18. Host-microbe interactions shaping the gastrointestinal environment

    PubMed Central

    Kaiko, Gerard E; Stappenbeck, Thaddeus S

    2014-01-01

    Tremendous strides have been made in mapping the complexity of the human gut microbiota in both health and disease states. These analyses have revealed that rather than a constellation of individual species, a healthy microbiota consists of an inter-dependent network of microbes. The microbial and host interactions that shape both this network and the gastrointestinal environment are areas of intense investigation. Here, we review emerging concepts of how microbial metabolic processes control commensal composition, invading pathogens, immune activation, and intestinal barrier function. We posit that all these factors are critical for the maintenance of homeostasis and avoidance of overt inflammatory disease. A greater understanding of the underlying mechanisms will shed light on the pathogenesis of many diseases and guide new therapeutic interventions. PMID:25220948

  19. PAK in pathogen-host interactions

    PubMed Central

    Semblat, Jean-Philippe; Doerig, Christian

    2012-01-01

    Eukaryotic, prokaryotic and viral pathogens are known to interfere with signaling pathways of their host to promote their own survival and proliferation. Here, we present selected examples of modulation of PAK activity in human cells by both intracellular and extracellular pathogens, focusing on one eukaryotic pathogen, the human malaria parasite Plasmodium falciparum, two Gram-negative bacteria (Helicobacter pylori and Pseudomonas aeruginosa), and two viruses belonging to distinct groups, the lentivirus HIV and the orthomyxovirus Influenza virus A. PMID:23125952

  20. New Insights into Molecular Ehrlichia chaffeensis-Host Interactions

    PubMed Central

    Wakeel, Abdul; Zhu, Bing; Yu, Xue-jie; McBride, Jere W.

    2010-01-01

    Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes and survives by reprogramming the host cell. Here we review new information regarding the newly characterized effector molecules and the complex network of molecular host-pathogen interactions that the organism exploits enabling it to thrive and persist intracellularly. PMID:20116446

  1. 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

  2. Sialomes and Mialomes: A Systems-Biology View of Tick Tissues and Tick-Host Interactions.

    PubMed

    Chmelař, Jindřich; Kotál, Jan; Karim, Shahid; Kopacek, Petr; Francischetti, Ivo M B; Pedra, Joao H F; Kotsyfakis, Michail

    2016-03-01

    Tick saliva facilitates tick feeding and infection of the host. Gene expression analysis of tick salivary glands and other tissues involved in host-pathogen interactions has revealed a wide range of bioactive tick proteins. Transcriptomic analysis has been a milestone in the field and has recently been enhanced by next-generation sequencing (NGS). Furthermore, the application of quantitative proteomics to ticks with unknown genomes has provided deeper insights into the molecular mechanisms underlying tick hematophagy, pathogen transmission, and tick-host-pathogen interactions. We review current knowledge on the transcriptomics and proteomics of tick tissues from a systems-biology perspective and discuss future challenges in the field. PMID:26520005

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

    PubMed

    Langhorne, Jean; Duffy, Patrick E

    2016-02-01

    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. PMID:26834158

  4. Interactions of porcine circovirus 2 with its hosts.

    PubMed

    Ren, Linzhu; Chen, Xinrong; Ouyang, Hongsheng

    2016-08-01

    Porcine circovirus 2 (PCV2) can cause porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are widely presented in swine-producing countries. Since the discovery of this virus, considerable efforts have been devoted to understanding this pathogen and its interactions with its host. Here, we review the current state of knowledge on interactions between host cell factors and PCV2 with respect to viral proliferation, virus-induced cell apoptosis and autophagy, and host antiviral defenses during PCV2 infection. We also review mouse model systems for PCV2 infection. PMID:27016220

  5. Bizarre interactions and endgames: entomopathogenic fungi and their arthropod hosts.

    PubMed

    Roy, H E; Steinkraus, D C; Eilenberg, J; Hajek, A E; Pell, J K

    2006-01-01

    Invertebrate pathogens and their hosts are taxonomically diverse. Despite this, there is one unifying concept relevant to all such parasitic associations: Both pathogen and host adapt to maximize their own reproductive output and ultimate fitness. The strategies adopted by pathogens and hosts to achieve this goal are almost as diverse as the organisms themselves, but studies examining such relationships have traditionally concentrated only on aspects of host physiology. Here we review examples of host-altered behavior and consider these within a broad ecological and evolutionary context. Research on pathogen-induced and host-mediated behavioral changes demonstrates the range of altered behaviors exhibited by invertebrates including behaviorally induced fever, elevation seeking, reduced or increased activity, reduced response to semiochemicals, and changes in reproductive behavior. These interactions are sometimes quite bizarre, intricate, and of great scientific interest. PMID:16332215

  6. 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.

  7. Wolbachia-Host Interactions: Host Mating Patterns Affect Wolbachia Density Dynamics

    PubMed Central

    Zhao, Dong-Xiao; Zhang, Xiang-Fei; Chen, Da-Song; Zhang, Yan-Kai; Hong, Xiao-Yue

    2013-01-01

    Wolbachia are maternally inherited intracellular bacteria that infect a wide range of arthropods and cause an array of effects on host reproduction, fitness and mating behavior. Although our understanding of the Wolbachia-associated effects on hosts is rapidly expanding, our knowledge of the host factors that mediate Wolbachia dynamics is rudimentary. Here, we explore the interactions between Wolbachia and its host, the two-spotted spider mite Tetranychus urticae Koch. Our results indicate that Wolbachia induces strong cytoplasmic incompatibility (CI), increases host fecundity, but has no effects on the longevity of females and the mating competitiveness of males in T. urticae. Most importantly, host mating pattern was found to affect Wolbachia density dynamics during host aging. Mating of an uninfected mite of either sex with an infected mite attenuates the Wolbachia density in the infected mite. According to the results of Wolbachia localization, this finding may be associated with the tropism of Wolbachia for the reproductive tissue in adult spider mites. Our findings describe a new interaction between Wolbachia and their hosts. PMID:23823081

  8. 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. PMID:26718485

  9. 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. PMID:26150659

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

    PubMed Central

    Strandh, Maria; Råberg, Lars

    2015-01-01

    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. PMID:26150659

  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. LuxS signaling in Porphyromonas gingivalis-host interactions.

    PubMed

    Scheres, Nina; Lamont, Richard J; Crielaard, Wim; Krom, Bastiaan P

    2015-10-01

    Dental plaque is a multispecies biofilm in the oral cavity that significantly influences oral health. The presence of the oral anaerobic pathogen Porphyromonas gingivalis is an important determinant in the development of periodontitis. Direct and indirect interactions between P. gingivalis and the host play a major role in disease development. Transcriptome analysis recently revealed that P. gingivalis gene-expression is regulated by LuxS in both an AI-2-dependent and an AI-2 independent manner. However, little is known about the role of LuxS-signaling in P. gingivalis-host interactions. Here, we investigated the effect of a luxS mutation on the ability of P. gingivalis to induce an inflammatory response in human oral cells in vitro. Primary periodontal ligament (PDL) fibroblasts were challenged with P. gingivalis ΔluxS or the wild-type parental strain and gene-expression of pro-inflammatory mediators IL-1β, IL-6 and MCP-1 was determined by real-time PCR. The ability of P. gingivalis ΔluxS to induce an inflammatory response was severely impaired in PDL-fibroblasts. This phenotype could be restored by providing of LuxS in trans, but not by addition of the AI-2 precursor DPD. A similar phenomenon was observed in a previous transcriptome study showing that expression of PGN_0482 was reduced in the luxS mutant independently of AI-2. We therefore also analyzed the effect of a mutation in PGN_0482, which encodes an immuno-reactive, putative outer-membrane protein. Similar to P. gingivalis ΔluxS, the P. gingivalis Δ0482 mutant had an impaired ability to induce an inflammatory response in PDL fibroblasts. LuxS thus appears to influence the pro-inflammatory responses of host cells to P. gingivalis, likely through regulation of PGN_0482. PMID:25434960

  13. 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

  14. Viruses, microRNAs, and Host Interactions

    PubMed Central

    Skalsky, Rebecca L.; Cullen, Bryan R.

    2013-01-01

    The most significant recent advance in biomedical research has been the discovery of the~22-nt long class of non-coding RNAs designated as microRNAs (miRNAs). These regulatory RNAs provide a unique level of post-transcriptional gene regulation that modulates a range of fundamental cellular processes. Several viruses, including especially herpesviruses, also encode miRNAs and over 200 viral miRNAs have now been identified. Current evidence indicates that viruses use these miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here we discuss our current knowledge of viral miRNAs and virally-influenced cellular miRNAs, and their relationship to viral infection. PMID:20477536

  15. 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.

  16. Host-microbiome interactions in acute and chronic respiratory infections.

    PubMed

    Taylor, Steven L; Wesselingh, Steve; Rogers, Geraint B

    2016-05-01

    Respiratory infection is a leading cause of global morbidity and mortality. Understanding the factors that influence risk and outcome of these infections is essential to improving care. We increasingly understand that interactions between the microbial residents of our mucosal surfaces and host regulatory systems is fundamental to shaping local and systemic immunity. These mechanisms are most well defined in the gastrointestinal tract, however analogous systems also occur in the airways. Moreover, we now appreciate that the host-microbiota interactions at a given mucosal surface influence systemic host processes, in turn, affecting the course of infection at other anatomical sites. This review discusses the mechanisms by which the respiratory microbiome influences acute and chronic airway disease and examines the contribution of cross-talk between the gastrointestinal and respiratory compartments to microbe-mucosa interactions. PMID:26972325

  17. Tree phylogenetic diversity promotes host-parasitoid interactions.

    PubMed

    Staab, Michael; Bruelheide, Helge; Durka, Walter; Michalski, Stefan; Purschke, Oliver; Zhu, Chao-Dong; Klein, Alexandra-Maria

    2016-07-13

    Evidence from grassland experiments suggests that a plant community's phylogenetic diversity (PD) is a strong predictor of ecosystem processes, even stronger than species richness per se This has, however, never been extended to species-rich forests and host-parasitoid interactions. We used cavity-nesting Hymenoptera and their parasitoids collected in a subtropical forest as a model system to test whether hosts, parasitoids, and their interactions are influenced by tree PD and a comprehensive set of environmental variables, including tree species richness. Parasitism rate and parasitoid abundance were positively correlated with tree PD. All variables describing parasitoids decreased with elevation, and were, except parasitism rate, dependent on host abundance. Quantitative descriptors of host-parasitoid networks were independent of the environment. Our study indicates that host-parasitoid interactions in species-rich forests are related to the PD of the tree community, which influences parasitism rates through parasitoid abundance. We show that effects of tree community PD are much stronger than effects of tree species richness, can cascade to high trophic levels, and promote trophic interactions. As during habitat modification phylogenetic information is usually lost non-randomly, even species-rich habitats may not be able to continuously provide the ecosystem process parasitism if the evolutionarily most distinct plant lineages vanish. PMID:27383815

  18. Interactions of bovine and caprine herpesviruses with the natural and the foreign hosts.

    PubMed

    Engels, M; Palatini, M; Metzler, A E; Probst, U; Kihm, U; Ackermann, M

    1992-11-01

    Bovine herpesvirus 1 (BHV1) and caprine herpesvirus 1 (CapHV1) are useful models to study virus-host interactions, as well as pathogenicity and latency, when comparing the outcome of infection in the natural and the foreign hosts. Molecular seroepidemiological analyses revealed that cross-reacting antibodies were mainly induced by glycoprotein gI (gB analogue), by the major capsid protein and by nonstructural proteins, whereas the most virus-specific antibodies were elicited by glycoproteins gIII and gIV. These glycoproteins, especially gIII (gC analogue), might therefore play an important role in the virus-host-interactions. As a basis for further studies, we re-evaluated observations concerning experimental infections with BHV1 and CapHV1 in the natural and the foreign hosts. All parameters indicated that both viruses were able to infect either host, but that the pathogenicity was restricted to the natural host. Latent virus could be reactivated exclusively from cows infected with BHV1. It was possible neither to reactivate BHV1 from goats, nor to reactivate CapHV1 from either species. The experiments indicated that the outcome of infection in the natural and the foreign host is dependent on host and viral factors, whereby gIII is only one important virus component involved. Further investigations in the host and host cell range of BHV1 and CapHV1 will help to clarify the role of factors responsible for virus-host-interactions. PMID:1336252

  19. 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

  20. 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.

  1. 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

  2. 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. PMID:27464694

  3. 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

    2016-03-01

    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

  4. Mathematical model of mycobacterium-host interaction describes physiology of persistence.

    PubMed

    Pedruzzi, Gabriele; Rao, Kanury V S; Chatterjee, Samrat

    2015-07-01

    Despite extensive studies on the interactions between Mycobacterium tuberculosis (M.tb) and macrophages, the mechanism by which pathogen evades anti-microbial responses and establishes persistence within the host cell remains unknown. In this study, we developed a four-dimensional ODE model to describe the dynamics of host-pathogen interactions in the early phase of macrophage infection. The aim was to characterize the role of host cellular regulators such as iron and lipids, in addition to the bactericidal effector molecule Nitric Oxide. Conditions for existence and stability of the equilibrium point were analysed by examining the behaviour of the model through numerical simulations. These computational investigations revealed that it was the ability of pathogen to interfere with iron and lipid homeostatic pathways of the host cell, which ensured a shift in balance towards pathogen survival and persistence. Interestingly, small perturbations in this equilibrium triggered the cell's bactericidal response, thereby producing an oscillatory dynamic for disease progression. PMID:25865521

  5. Virus-Host Interactions: From Unbiased Genetic Screens to Function.

    PubMed

    Ramage, Holly; Cherry, Sara

    2015-11-01

    Deciphering the many interactions that occur between a virus and host cell over the course of infection is paramount to understanding mechanisms of pathogenesis and to the future development of antiviral therapies. Over the past decade, researchers have started to understand these complicated relationships through the development of methodologies, including advances in RNA interference, proteomics, and the development of genetic tools such as haploid cell lines, allowing high-throughput screening to identify critical contact points between virus and host. These advances have produced a wealth of data regarding host factors hijacked by viruses to promote infection, as well as antiviral factors responsible for subverting viral infection. This review highlights findings from virus-host screens and discusses our thoughts on the direction of screening strategies moving forward. PMID:26958926

  6. Zika virus: epidemiology, clinical features and host-virus interactions.

    PubMed

    Hamel, Rodolphe; Liégeois, Florian; Wichit, Sineewanlaya; Pompon, Julien; Diop, Fodé; Talignani, Loïc; Thomas, Frédéric; Desprès, Philippe; Yssel, Hans; Missé, Dorothée

    2016-01-01

    Very recently, Zika virus (ZIKV) has gained a medical importance following the large-scale epidemics in South Pacific and Latin America. This paper reviews information on the epidemiology and clinical features of Zika disease with a particular emphasis on the host-virus interactions that contribute to the pathogenicity of ZIKV in humans. PMID:27012221

  7. 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 ...

  8. Porphyromonas gingivalis-host interactions in a Drosophila melanogaster model.

    PubMed

    Igboin, Christina O; Tordoff, Kevin P; Moeschberger, Melvin L; Griffen, Ann L; Leys, Eugene J

    2011-01-01

    Porphyromonas gingivalis is a Gram-negative obligate anaerobe that has been implicated in the etiology of adult periodontitis. We recently introduced a Drosophila melanogaster killing model for examination of P. gingivalis-host interactions. In the current study, the Drosophila killing model was used to characterize the host response to P. gingivalis infection by identifying host components that play a role during infection. Drosophila immune response gene mutants were screened for altered susceptibility to killing by P. gingivalis. The Imd signaling pathway was shown to be important for the survival of Drosophila infected by nonencapsulated P. gingivalis strains but was dispensable for the survival of Drosophila infected by encapsulated P. gingivalis strains. The P. gingivalis capsule was shown to mediate resistance to killing by Drosophila antimicrobial peptides (Imd pathway-regulated cecropinA and drosocin) and human beta-defensin 3. Drosophila thiol-ester protein II (Tep II) and Tep IV and the tumor necrosis factor (TNF) homolog Eiger were also involved in the immune response against P. gingivalis infection, while the scavenger receptors Eater and Croquemort played no roles in the response to P. gingivalis infection. This study demonstrates that the Drosophila killing model is a useful high-throughput model for characterizing the host response to P. gingivalis infection and uncovering novel interactions between the bacterium and the host. PMID:21041486

  9. Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions.

    PubMed

    Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A

    2016-01-01

    Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. PMID:27131329

  10. Evolved plasmid-host interactions reduce plasmid interference cost.

    PubMed

    Yano, Hirokazu; Wegrzyn, Katarznya; Loftie-Eaton, Wesley; Johnson, Jenny; Deckert, Gail E; Rogers, Linda M; Konieczny, Igor; Top, Eva M

    2016-09-01

    Antibiotic selection drives adaptation of antibiotic resistance plasmids to new bacterial hosts, but the molecular mechanisms are still poorly understood. We previously showed that a broad-host-range plasmid was poorly maintained in Shewanella oneidensis, but rapidly adapted through mutations in the replication initiation gene trfA1. Here we examined if these mutations reduced the fitness cost of TrfA1, and whether this was due to changes in interaction with the host's DNA helicase DnaB. The strains expressing evolved TrfA1 variants showed a higher growth rate than those expressing ancestral TrfA1. The evolved TrfA1 variants showed a lower affinity to the helicase than ancestral TrfA1 and were no longer able to activate the helicase at the oriV without host DnaA. Moreover, persistence of the ancestral plasmid was increased upon overexpression of DnaB. Finally, the evolved TrfA1 variants generated higher plasmid copy numbers than ancestral TrfA1. The findings suggest that ancestral plasmid instability can at least partly be explained by titration of DnaB by TrfA1. Thus under antibiotic selection resistance plasmids can adapt to a novel bacterial host through partial loss of function mutations that simultaneously increase plasmid copy number and decrease unfavorably high affinity to one of the hosts' essential proteins. PMID:27121483

  11. Proteomic characterization of a natural host-pathogen interaction: repertoire of in vivo expressed bacterial and host surface-associated proteins.

    PubMed

    Rees, Megan A; Kleifeld, Oded; Crellin, Paul K; Ho, Bosco; Stinear, Timothy P; Smith, A Ian; Coppel, Ross L

    2015-01-01

    Interactions between a host and a bacterial pathogen are mediated by cross-talk between molecules present on, or secreted by, pathogens and host binding-molecules. Identifying proteins involved at this interface would provide substantial insights into this interaction. Although numerous studies have examined in vitro models of infection at the level of transcriptional change and proteomic profiling, there is virtually no information available on naturally occurring host-pathogen interactions in vivo. We employed membrane shaving to identify peptide fragments cleaved from surface-expressed bacterial proteins and also detected proteins originating from the infected host. We optimized this technique for media-cultured Corynebacterium pseudotuberculosis, a sheep pathogen, revealing a set of 247 surface proteins. We then studied a natural host-pathogen interaction by performing membrane shaving on C. pseudotuberculosis harvested directly from naturally infected sheep lymph nodes. Thirty-one bacterial surface proteins were identified, including 13 not identified in culture media, suggesting that a different surface protein repertoire is expressed in this hostile environment. Forty-nine host proteins were identified, including immune mediators and antimicrobial peptides such as cathelicidin. This novel application of proteolytic shaving has documented sets of host and pathogen proteins present at the bacterial surface in an infection of the native host. PMID:25329524

  12. Empirical evaluation of neutral interactions in host-parasite networks.

    PubMed

    Canard, E F; Mouquet, N; Mouillot, D; Stanko, M; Miklisova, D; Gravel, D

    2014-04-01

    While niche-based processes have been invoked extensively to explain the structure of interaction networks, recent studies propose that neutrality could also be of great importance. Under the neutral hypothesis, network structure would simply emerge from random encounters between individuals and thus would be directly linked to species abundance. We investigated the impact of species abundance distributions on qualitative and quantitative metrics of 113 host-parasite networks. We analyzed the concordance between neutral expectations and empirical observations at interaction, species, and network levels. We found that species abundance accurately predicts network metrics at all levels. Despite host-parasite systems being constrained by physiology and immunology, our results suggest that neutrality could also explain, at least partially, their structure. We hypothesize that trait matching would determine potential interactions between species, while abundance would determine their realization. PMID:24642492

  13. 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

  14. Host-Microbe Interactions in Microgravity: Assessment and Implications

    PubMed Central

    Foster, Jamie S.; Wheeler, Raymond M.; Pamphile, Regine

    2014-01-01

    Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes. PMID:25370197

  15. Leptospira spp.: Novel insights into host-pathogen interactions.

    PubMed

    Fernandes, Luis G; Siqueira, Gabriela H; Teixeira, Aline R F; Silva, Lucas P; Figueredo, Jupciana M; Cosate, Maria R; Vieira, Monica L; Nascimento, Ana L T O

    2016-08-01

    Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is an important infectious disease that affects humans and animals. The disease causes economic losses as it affects livestock, with decreased milk production and death. Our group is investigating the genome sequences of L. interrogans targeting surface-exposed proteins because, due to their location, these proteins are capable to interact with several host components that could allow establishment of the infection. These interactions may involve adhesion of the bacteria to extracellular matrix (ECM) components and, hence, help bacterial colonization. The bacteria could also react with the host fibrinolytic system and/or with the coagulation cascade components, such as, plasminogen (PLG) and fibrinogen (Fg), respectively. The binding with the first system generates plasmin (PLA), increasing the proteolytic power of the bacteria, while the second interferes with clotting in a thrombin-catalyzed reaction, which may promote hemorrhage foci and increase bacterial dissemination. Interaction with the complement system negative regulators may help bacteria to evade the host immune system, facilitating the invasion. This work compiles the main described leptospiral proteins that could act as adhesins, as PLG and fibrinogen receptors and as complement regulator binding proteins. We present models in which we suggest possible mechanisms of how leptospires might colonize and invade host tissues, causing the disease. Understanding leptospiral pathogenesis will help to identify antigen candidates that would contribute to the development of more effective vaccines and diagnostic tests. PMID:26727033

  16. Host-microbe interactions in the gut of Drosophila melanogaster

    PubMed Central

    Kuraishi, Takayuki; Hori, Aki; Kurata, Shoichiro

    2013-01-01

    Many insect species subsist on decaying and contaminated matter and are thus exposed to large quantities of microorganisms. To control beneficial commensals and combat infectious pathogens, insects must be armed with efficient systems for microbial recognition, signaling pathways, and effector molecules. The molecular mechanisms regulating these host-microbe interactions in insects have been largely clarified in Drosophila melanogaster with its powerful genetic and genomic tools. Here we review recent advances in this field, focusing mainly on the relationships between microbes and epithelial cells in the intestinal tract where the host exposure to the external environment is most frequent. PMID:24381562

  17. 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

  18. Salmonella-host interactions - modulation of the host innate immune system.

    PubMed

    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

  19. Microbe–Host Interactions are Positively and Negatively Regulated by Galectin–Glycan Interactions

    PubMed Central

    Baum, Linda G.; Garner, Omai B.; Schaefer, Katrin; Lee, Benhur

    2014-01-01

    Microbe–host interactions are complex processes that are directly and indirectly regulated by a variety of factors, including microbe presentation of specific molecular signatures on the microbial surface, as well as host cell presentation of receptors that recognize these pathogen signatures. Cell surface glycans are one important class of microbial signatures that are recognized by a variety of host cell lectins. Host cell lectins that recognize microbial glycans include members of the galectin family of lectins that recognize specific glycan ligands on viruses, bacteria, fungi, and parasites. In this review, we will discuss the ways that the interactions of microbial glycans with host cell galectins positively and negatively regulate pathogen attachment, invasion, and survival, as well as regulate host responses that mitigate microbial pathogenesis. PMID:24995007

  20. Virus-Host Mucosal Interactions During Early SIV Rectal Transmission

    PubMed Central

    Lu, Wuxun; Ma, Fangrui; Churbanov, Alexander; Wan, Yanmin; Li, Yue; Kang, Guobin; Yuan, Zhe; Wang, Dong; Zhang, Chi; Xu, Jianqing; Lewis, Mark; Li, Qingsheng

    2016-01-01

    To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggests that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into mucosa; and a high-level expression of SIV accessory genes, which are known to be able to counter and evade host restriction factors and innate immune responses. This study provides new insights into the mechanism of rectal transmission. PMID:25128762

  1. Understanding complex host-microbe interactions in Hydra

    PubMed Central

    Bosch, Thomas C.G.

    2012-01-01

    Any multicellular organism may be considered a metaorganism or holobiont—comprised of the macroscopic host and synergistic interdependence with bacteria, archaea, fungi, viruses, and numerous other microbial and eukaryotic species including algal symbionts. Defining the individual microbe-host conversations in these consortia is a challenging but necessary step on the path to understanding the function of the associations as a whole. Dissecting the fundamental principles that underlie all host-microbe interactions requires simple animal models with only a few specific bacterial species. Here I present Hydra as such a model with one of the simplest epithelia in the animal kingdom, with the availability of a fully sequenced genome and numerous genomic tools, and with few associated bacterial species. PMID:22688725

  2. 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

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

    PubMed

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

    2016-05-01

    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. PMID:26833861

  4. Searching for Magnetic Interactions Between Exoplanets and Their Host Stars

    NASA Astrophysics Data System (ADS)

    Saken, JoN M.; Gray, R. O.; Flora, C. T.; Izlar, K. A.

    2008-05-01

    A large fraction of the known exoplanets are so called "hot-Jupiters", planets with roughly Jovian mass and orbits that bring them fairly close to their host stars. Assuming that their properties are somewhat similar to the gas giants in our own solar system, such planets might be expected to produce enhanced chromospheric activity in their host stars via magnetic interactions. Investigations of these interactions can help shed light on the nature and character of exoplanet magnetospheres. [To date, only one such interaction has been observed, in HD179949 (Shkolnik 2005).] Recently we have begun a long-term spectroscopic campaign at Appalachian State University's Dark Sky Observatory, monitoring the chromospheric activity of stars with exoplanets orbiting within 0.25 AU. The monitoring of host stars over a long time frame is important,since interactions may only be detectable when the stars are in an "active" state. Preliminary results from the first year of observations will be presented here. Support provided by NC SpaceGrant.

  5. 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

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

    PubMed

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

    2016-03-01

    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. PMID:25905427

  7. Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface

    PubMed Central

    Juranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne

    2013-01-01

    Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. PMID:24086132

  8. Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial regulation.

    PubMed

    Luckhart, Shirley; Pakpour, Nazzy; Giulivi, Cecilia

    2015-10-01

    Malaria parasite-host interactions are complex and have confounded available drugs and the development of vaccines. Further, we now appreciate that interventions for malaria elimination and eradication must include therapeutics with intrinsic transmission blocking activity to treat the patient and prevent disease spread. Studies over the past 15 years have revealed significant conservation in the response to infection in mosquito and human hosts. More recently, we have recognized that conserved cell signaling cascades in mosquitoes and humans dictate infection outcome through the regulation of mitochondrial function and biogenesis, which feed back to host immunity, basic intermediary metabolism, and stress responses. These responses - reflected clearly in the primeval insect host - provide fertile ground for innovative strategies for both treatment and transmission blocking. PMID:26210301

  9. Protozoa lectins and their role in host-pathogen interactions.

    PubMed

    Singh, Ram Sarup; Walia, Amandeep Kaur; Kanwar, Jagat Rakesh

    2016-01-01

    Lectins are proteins/glycoproteins of non-immune origin that agglutinate red blood cells, lymphocytes, fibroblasts, etc., and bind reversibly to carbohydrates present on the apposing cells. They have at least two carbohydrate binding sites and their binding can be inhibited by one or more carbohydrates. Owing to carbohydrate binding specificity of lectins, they mediate cell-cell interactions and play role in protozoan adhesion and host cell cytotoxicity, thus are central to the pathogenic property of the parasite. Several parasitic protozoa possess lectins which mediate parasite adherence to host cells based on their carbohydrate specificities. These interactions could be exploited for development of novel therapeutics, targeting the adherence and thus helpful in eradicating wide spread of protozoan diseases. The current review highlights the present state knowledge with regard to protozoal lectins with an emphasis on their haemagglutination activity, carbohydrate specificity, characteristics and also their role in pathogenesis notably as adhesion molecules, thereby aiding the pathogen in disease establishment. PMID:27268207

  10. Bioinformatic Prediction of WSSV-Host Protein-Protein Interaction

    PubMed Central

    Sun, Zheng; Xiang, Jianhai

    2014-01-01

    WSSV is one of the most dangerous pathogens in shrimp aquaculture. However, the molecular mechanism of how WSSV interacts with shrimp is still not very clear. In the present study, bioinformatic approaches were used to predict interactions between proteins from WSSV and shrimp. The genome data of WSSV (NC_003225.1) and the constructed transcriptome data of F. chinensis were used to screen potentially interacting proteins by searching in protein interaction databases, including STRING, Reactome, and DIP. Forty-four pairs of proteins were suggested to have interactions between WSSV and the shrimp. Gene ontology analysis revealed that 6 pairs of these interacting proteins were classified into “extracellular region” or “receptor complex” GO-terms. KEGG pathway analysis showed that they were involved in the “ECM-receptor interaction pathway.” In the 6 pairs of interacting proteins, an envelope protein called “collagen-like protein” (WSSV-CLP) encoded by an early virus gene “wsv001” in WSSV interacted with 6 deduced proteins from the shrimp, including three integrin alpha (ITGA), two integrin beta (ITGB), and one syndecan (SDC). Sequence analysis on WSSV-CLP, ITGA, ITGB, and SDC revealed that they possessed the sequence features for protein-protein interactions. This study might provide new insights into the interaction mechanisms between WSSV and shrimp. PMID:24982879

  11. 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. PMID:18595836

  12. 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. PMID:26405832

  13. 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

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

    PubMed

    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

  15. 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

  16. Modelling the interaction between bacteriophages and their bacterial hosts.

    PubMed

    Beke, Gabor; Stano, Matej; Klucar, Lubos

    2016-09-01

    A mathematical model simulating the interaction between bacteriophages and their bacterial hosts has been developed. It is based on other known models describing this type of interaction, enhanced with an ability to model the system influenced by other environmental factor such as pH and temperature. This could be used for numerous estimations of growth rate, when the pH and/or the temperature of the environment are not constant. The change of pH or the temperature greatly affects the specific growth rate which has an effect on the final results of the simulation. Since the model aims on practical application and easy accessibility, an interactive website has been developed where users can run simulations with their own parameters and easily calculate and visualise the result of simulation. The web simulation is accessible at the URL http://www.phisite.org/model. PMID:27393678

  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…

  18. 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...

  19. Identification of host proteins, Spata3 and Dkk2, interacting with Toxoplasma gondii micronemal protein MIC3.

    PubMed

    Wang, Yifan; Fang, Rui; Yuan, Yuan; Pan, Ming; Hu, Min; Zhou, Yanqin; Shen, Bang; Zhao, Junlong

    2016-07-01

    As an obligate intracellular protozoan, Toxoplasma gondii is a successful pathogen infecting a variety of animals, including humans. As an adhesin involving in host invasion, the micronemal protein MIC3 plays important roles in host cell attachment, as well as modulation of host EGFR signaling cascade. However, the specific host proteins that interact with MIC3 are unknown and the identification of such proteins will increase our understanding of how MIC3 exerts its functions. This study was designed to identify host proteins interacting with MIC3 by yeast two-hybrid screens. Using MIC3 as bait, a library expressing mouse proteins was screened, uncovering eight mouse proteins that showed positive interactions with MIC3. Two of which, spermatogenesis-associated protein 3 (Spata3) and dickkopf-related protein 2 (Dkk2), were further confirmed to interact with MIC3 by additional protein-protein interaction tests. The results also revealed that the tandem repeat EGF domains of MIC3 were critical in mediating the interactions with the identified host proteins. This is the first study to show that MIC3 interacts with host proteins that are involved in reproduction, growth, and development. The results will provide a clearer understanding of the functions of adhesion-associated micronemal proteins in T. gondii. PMID:27053129

  20. The EHEC-host interactome reveals novel targets for the translocated intimin receptor.

    PubMed

    Blasche, Sonja; Arens, Stefan; Ceol, Arnaud; Siszler, Gabriella; Schmidt, M Alexander; Häuser, Roman; Schwarz, Frank; Wuchty, Stefan; Aloy, Patrick; Uetz, Peter; Stradal, Theresia; Koegl, Manfred

    2014-01-01

    Enterohemorrhagic E. coli (EHEC) manipulate their human host through at least 39 effector proteins which hijack host processes through direct protein-protein interactions (PPIs). To identify their protein targets in the host cells, we performed yeast two-hybrid screens, allowing us to find 48 high-confidence protein-protein interactions between 15 EHEC effectors and 47 human host proteins. In comparison to other bacteria and viruses we found that EHEC effectors bind more frequently to hub proteins as well as to proteins that participate in a higher number of protein complexes. The data set includes six new interactions that involve the translocated intimin receptor (TIR), namely HPCAL1, HPCAL4, NCALD, ARRB1, PDE6D, and STK16. We compared these TIR interactions in EHEC and enteropathogenic E. coli (EPEC) and found that five interactions were conserved. Notably, the conserved interactions included those of serine/threonine kinase 16 (STK16), hippocalcin-like 1 (HPCAL1) as well as neurocalcin-delta (NCALD). These proteins co-localize with the infection sites of EPEC. Furthermore, our results suggest putative functions of poorly characterized effectors (EspJ, EspY1). In particular, we observed that EspJ is connected to the microtubule system while EspY1 appears to be involved in apoptosis/cell cycle regulation. PMID:25519916

  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. Revealing protein–lncRNA interaction

    PubMed Central

    Colantoni, Alessio; Helmer-Citterich, Manuela

    2016-01-01

    Long non-coding RNAs (lncRNAs) are associated to a plethora of cellular functions, most of which require the interaction with one or more RNA-binding proteins (RBPs); similarly, RBPs are often able to bind a large number of different RNAs. The currently available knowledge is already drawing an intricate network of interactions, whose deregulation is frequently associated to pathological states. Several different techniques were developed in the past years to obtain protein–RNA binding data in a high-throughput fashion. In parallel, in silico inference methods were developed for the accurate computational prediction of the interaction of RBP–lncRNA pairs. The field is growing rapidly, and it is foreseeable that in the near future, the protein–lncRNA interaction network will rise, offering essential clues for a better understanding of lncRNA cellular mechanisms and their disease-associated perturbations. PMID:26041786

  3. 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

  4. 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

  5. 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

    2016-01-01

    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

  6. 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. PMID:26863542

  7. 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

  8. Altered host cell-bacteria interaction due to nanoparticle interaction with a bacterial biofilm.

    PubMed

    Raftery, Tara D; Lindler, Heidi; McNealy, Tamara L

    2013-02-01

    Nanoparticle (NP) use in everyday applications creates the potential for NPs to enter the environment where, in aquatic systems, they are likely to settle on substrates and interact with microbial communities. Legionella pneumophila biofilms are found as part of microbial communities in both natural and man-made environments, especially in man-made cooling systems. The bacterium is the causative agent of Legionnaires' disease. Legionella requires a host cell for replication in the environment, and amoebae commonly serve as this host cell. Our previous work demonstrated significant changes in Legionella biofilm morphology after exposure to 0.7 μg/L gold NPs (AuNPs). Here, we investigate how these morphology changes alter host-bacteria interactions using Acanthamoeba polyphaga as a model. Host-bacteria-NP interactions are affected by NP characteristics. Biofilms exposed to 4- and 18-nm, citrate-capped, spherical AuNPs significantly altered the grazing ability of A. polyphaga, which was not observed in biofilms exposed to 24-nm polystyrene beads. Uptake and replication of NP-exposed planktonic L. pneumophila within A. polyphaga were not altered regardless of NP size or core chemistry. Nanomaterial effects on the interaction of benthic organisms and bacteria may be directly or, as shown here, indirectly dependent on bacterial morphology. NP contamination therefore may alter interactions in a normal ecosystem function. PMID:23052925

  9. Networks of Host Factors that Interact with NS1 Protein of Influenza A Virus

    PubMed Central

    Thulasi Raman, Sathya N.; Zhou, Yan

    2016-01-01

    Pigs are an important host of influenza A viruses due to their ability to generate reassortant viruses with pandemic potential. NS1 protein of influenza A viruses is a key virulence factor and a major antagonist of innate immune responses. It is also involved in enhancing viral mRNA translation and regulation of virus replication. Being a protein with pleiotropic functions, NS1 has a variety of cellular interaction partners. Hence, studies on swine influenza viruses (SIV) and identification of swine influenza NS1-interacting host proteins is of great interest. Here, we constructed a recombinant SIV carrying a Strep-tag in the NS1 protein and infected primary swine respiratory epithelial cells (SRECs) with this virus. The Strep-tag sequence in the NS1 protein enabled us to purify intact, the NS1 protein and its interacting protein complex specifically. We identified cellular proteins present in the purified complex by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and generated a dataset of these proteins. 445 proteins were identified by LC-MS/MS and among them 192 proteins were selected by setting up a threshold based on MS parameters. The selected proteins were analyzed by bioinformatics and were categorized as belonging to different functional groups including translation, RNA processing, cytoskeleton, innate immunity, and apoptosis. Protein interaction networks were derived using these data and the NS1 interactions with some of the specific host factors were verified by immunoprecipitation. The novel proteins and the networks revealed in our study will be the potential candidates for targeted study of the molecular interaction of NS1 with host proteins, which will provide insights into the identification of new therapeutic targets to control influenza infection and disease pathogenesis. PMID:27199973

  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. 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. PMID:26811798

  12. 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

  13. Host-pathogen interactions: leukocyte phagocytosis and associated sequelae.

    PubMed

    Voyich, Jovanka M; DeLeo, Frank R

    2002-01-01

    Polymorphonuclear leukocytes (PMNs) are a critical component of the human innate immune response and are the first line of defense against invading microorganisms. Phagocytosis of invading microbes induces production of reactive oxygen species (ROS) by PMNs, which facilitates bactericidal activity. In addition to eliminating microorganisms, phagocytosis also accelerates PMN apoptosis, a process critical for resolution of inflammation. Inasmuch as leukocyte phagocytosis and ROS production are key components of the innate immune response, we developed flow cytometric methods to evaluate these processes in human PMNs. In contrast to traditional microscopy-based analyses, the methods described herein provide objective and high throughput measures of host cell-pathogen interactions. Importantly, they can be adapted for use with a number of fluorometric probes, and bacterium and host cell of choice, and each is based upon a common phagocytosis assay system. We also describe methods to measure phagocytosis-induced PMN apoptosis with this assay system. These methods entail detecting surface-exposed phosphatidylserine (early apoptosis), and measuring PMN chromatin condensation and DNA fragmentation (late apoptosis). Taken together, these assays provide rapid and accurate assessment of critical PMN processes. PMID:12815296

  14. 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

  15. 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.

  16. Ehrlichia chaffeensis Transcriptome in Mammalian and Arthropod Hosts Reveals Differential Gene Expression and Post Transcriptional Regulation

    PubMed Central

    Kuriakose, Jeeba A.; Miyashiro, Simone; Luo, Tian; Zhu, Bing; McBride, Jere W.

    2011-01-01

    associated with host-pathogen interactions are differentially expressed and regulated by post transcriptional mechanisms. PMID:21915290

  17. 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...

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

    PubMed Central

    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.

    2014-01-01

    SUMMARY 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. PMID:25544563

  19. Understanding the complexities of Salmonella-host crosstalk as revealed by in vivo model organisms.

    PubMed

    Verma, Smriti; Srikanth, Chittur V

    2015-07-01

    Foodborne infections caused by non-typhoidal Salmonellae, such as Salmonella enterica serovar Typhimurium (ST), pose a major challenge in the developed and developing world. With constant rise of drug-resistant strains, understanding the epidemiology, microbiology, pathogenesis and host-pathogen interactions biology is a mandatory requirement to enable health systems to be ready to combat these illnesses. Patient data from hospitals, at least from some parts of the world, have aided in epidemiological understanding of ST-mediated disease. Most of the other aspects connected to Salmonella-host crosstalk have come from model systems that offer convenience, genetic tractability and low maintenance costs that make them extremely valuable tools. Complex model systems such as the bovine model have helped in understanding key virulence factors needed for infection. Simple systems such as fruit flies and Caenorhabditis elegans have aided in identification of novel virulence factors, host pathways and mechanistic details of interactions. Some of the path-breaking concepts of the field have come from mice model of ST colitis, which allows genetic manipulations as well as high degree of similarity to human counterpart. Together, they are invaluable for correlating in vitro findings of ST-induced disease progression in vivo. The current review is a compilation of various advances of ST-host interactions at cellular and molecular levels that has come from investigations involving model organisms. PMID:26179888

  20. 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

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

    PubMed

    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

    2015-10-01

    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. 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

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

    PubMed

    Guo, Ximing; Ford, Susan E

    2016-03-01

    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

  4. Environment, interactions between Trypanosoma cruzi and its host, and health.

    PubMed

    Teixeira, Antonio R L; Gomes, Clever; Lozzi, Silene P; Hecht, Mariana M; Rosa, Ana de Cássia; Monteiro, Pedro S; Bussacos, Ana Carolina; Nitz, Nadjar; McManus, Concepta

    2009-01-01

    An epidemiological chain involving Trypanosoma cruzi is discussed at the environmental level, and in terms of fine molecular interactions in invertebrate and vertebrate hosts dwelling in different ecosystems. This protozoan has a complex, genetically controlled plasticity, which confers adaptation to approximately 40 blood-sucking triatomine species and to over 1,000 mammalian species, fulfilling diverse metabolic requirements in its complex life-cycle. The Tr. cruzi infections are deeply embedded in countless ecotypes, where they are difficult to defeat using the control methods that are currently available. Many more field and laboratory studies are required to obtain data and information that may be used for the control and prevention of Tr. cruzi infections and their various disease manifestations. Emphasis should be placed on those sensitive interactions at cellular and environmental levels that could become selected targets for disease prevention. In the short term, new technologies for social mobilization should be used by people and organizations working for justice and equality through health information and promotion. A mass media directed program could deliver education, information and communication to protect the inhabitants at risk of contracting Tr. cruzi infections. PMID:19287864

  5. Granuloma Transplantation: An Approach to Study Mycobacterium–Host Interactions

    PubMed Central

    Harding, Jeffrey S.; Schreiber, Heidi A.; Sandor, Matyas

    2011-01-01

    The host–pathogen biology during infection with Mycobacterium tuberculosis is incredibly complex and despite accelerating progress in research, remains poorly understood. Our limited understanding hinders the development of new drugs, next generation vaccines, and novel therapies. The granuloma is the site where mycobacteria are both controlled and allowed to persist, but it remains one of the least studied aspects of the host–pathogen relationship. Here, we review the development, application, potential uses, and limitations of a novel model of granuloma transplantation as a tool to study specific host–pathogen interactions that have been difficult to probe. Application of this new model has already contributed to our understanding of granuloma cell traffic, repopulation, and the relationship between systemic immunity and mycobacteria-containing granulomas. The data collected highlight the dynamic interaction between systemic and local immune processes and support a paradigm that defines the granuloma as a highly dynamic structure. Granuloma transplantation also has special potential as a novel latency model that can contribute to our understanding of host protection factors and bacterial mutants, and serve as a platform for drug testing. PMID:22180751

  6. Parasite Transmission in Social Interacting Hosts: Monogenean Epidemics in Guppies

    PubMed Central

    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. PMID:21897838

  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-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. PMID:23871855

  10. Parasites destabilize host populations by shifting stage-structured interactions.

    PubMed

    Hite, Jessica L; Penczykowski, Rachel M; Shocket, Marta S; Strauss, Alexander T; Orlando, Paul A; Duffy, Meghan A; Cáceres, Carla E; Hall, Spencer R

    2016-02-01

    Should parasites stabilize or destabilize consumer-resource dynamics? Recent theory suggests that parasite-enhanced mortality may confer underappreciated stability to their hosts. We tested this hypothesis using disease in zooplankton. Across both natural and experimental epidemics, bigger epidemics correlated with larger--not smaller--host fluctuations. Thus, we tested two mechanistic hypotheses to explain destabilization or apparent destabilization by parasites. First, enrichment could, in principle, simultaneously enhance both instability and disease prevalence. In natural epidemics, destabilization was correlated with enrichment (indexed by total phosphorous). However, an in situ (lake enclosure) experiment did not support these links. Instead, field and experimental results point to a novel destabilizing mechanism involving host stage structure. Epidemics pushed hosts from relatively more stable host dynamics with less-synchronized juveniles and adults to less stable dynamics with more-synchronized juveniles and adults. Our results demonstrate how links between host stage structure and disease can shape host/consumer-resource stability. PMID:27145618

  11. The Integrative Taxonomic Approach Reveals Host Specific Species in an Encyrtid Parasitoid Species Complex

    PubMed Central

    Chesters, Douglas; Wang, Ying; Yu, Fang; Bai, Ming; Zhang, Tong-Xin; Hu, Hao-Yuan; Zhu, Chao-Dong; Li, Cheng-De; Zhang, Yan-Zhou

    2012-01-01

    Integrated taxonomy uses evidence from a number of different character types to delimit species and other natural groupings. While this approach has been advocated recently, and should be of particular utility in the case of diminutive insect parasitoids, there are relatively few examples of its application in these taxa. Here, we use an integrated framework to delimit independent lineages in Encyrtus sasakii (Hymenoptera: Chalcidoidea: Encyrtidae), a parasitoid morphospecies previously considered a host generalist. Sequence variation at the DNA barcode (cytochrome c oxidase I, COI) and nuclear 28S rDNA loci were compared to morphometric recordings and mating compatibility tests, among samples of this species complex collected from its four scale insect hosts, covering a broad geographic range of northern and central China. Our results reveal that Encyrtus sasakii comprises three lineages that, while sharing a similar morphology, are highly divergent at the molecular level. At the barcode locus, the median K2P molecular distance between individuals from three primary populations was found to be 11.3%, well outside the divergence usually observed between Chalcidoidea conspecifics (0.5%). Corroborative evidence that the genetic lineages represent independent species was found from mating tests, where compatibility was observed only within populations, and morphometric analysis, which found that despite apparent morphological homogeneity, populations clustered according to forewing shape. The independent lineages defined by the integrated analysis correspond to the three scale insect hosts, suggesting the presence of host specific cryptic species. The finding of hidden host specificity in this species complex demonstrates the critical role that DNA barcoding will increasingly play in revealing hidden biodiversity in taxa that present difficulties for traditional taxonomic approaches. PMID:22666375

  12. Effect of lactoferrin protein on red blood cells and macrophages: mechanism of parasite–host interaction

    PubMed Central

    Anand, Namrata; Kanwar, Rupinder K; Dubey, Mohan Lal; Vahishta, R K; Sehgal, Rakesh; Verma, Anita K; Kanwar, Jagat R

    2015-01-01

    details the interaction between lactoferrin and parasite host cells, ie, RBCs and macrophages, using various cellular processes and expression studies. The study reveals the possible mechanism of action against various intracellular pathogens such as Toxoplasma, Plasmodium, Leishmania, Trypanosoma, and Mycobacterium. The presence of iron in lactoferrin plays an important role in enhancing the various activities taking place inside these cells. This work provides a lot of information about targeting lactoferrin against many parasitic infections which can rule out the exact pathways for inhibition of diseases caused by intracellular microbes mainly targeting RBCs and macrophages for their survival. Therefore, this initial study can serve as a baseline for further evaluation of the mechanism of action of lactoferrin against parasitic diseases, which is not fully understood to date. PMID:26251568

  13. 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. PMID:23085046

  14. Evidence for additive and interaction effects of host genotype and infection in malaria

    PubMed Central

    Idaghdour, Youssef; Quinlan, Jacklyn; Goulet, Jean-Philippe; Berghout, Joanne; Gbeha, Elias; Bruat, Vanessa; de Malliard, Thibault; Grenier, Jean-Christophe; Gomez, Selma; Gros, Philippe; Rahimy, Mohamed Chérif; Sanni, Ambaliou; Awadalla, Philip

    2012-01-01

    The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children’s ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility. PMID:22949651

  15. Host-parasite interactions in closed and open microbial cultivation system

    NASA Astrophysics Data System (ADS)

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

    We studied interaction between bacteria and phages within a host-parasite system the members of the system being continuously and closely cultivated The objects of our research were auxotrophic strain Brevibacterium 22L and bacteriophage Brevibacterium sp strain A discovered in the soil of the Soviet Union Republic of Latvia using enrichment method 1 Closed system We investigated the dependence of bacteriolysis time upon the multiplicity of phage infection It was shown that reduction of phage amount by one bacterium leads to increase of marked lysis Another important factor determining cytolysis in fluid medium is the physiological state of bacterial population Specific growth rate of bacteria at the moment of phage infection was chosen as the index of the physiological state of bacteria It was revealed that the shortest latent period and the maximal phage burst is observed when the bacteria located in a favorable nutrient medium are in the logarithmic phase If the bacterial population has already passed from the logarithmic phase to the stationary one the cells become a bad host for phage reproduction and lysis occurs very slowly or even never starts at all 2 Open system In the process of continuous cultivation the members of the host-parasite system showed an ability to coexist over a long period of time After phage infection there were variations in the size of both populations and then the density of the host population reached the level close to that of the uninfected culture In this situation the phage population

  16. Gut microbiome-host interactions in health and disease

    PubMed Central

    2011-01-01

    The gut microbiome is the term given to describe the vast collection of symbiotic microorganisms in the human gastrointestinal system and their collective interacting genomes. Recent studies have suggested that the gut microbiome performs numerous important biochemical functions for the host, and disorders of the microbiome are associated with many and diverse human disease processes. Systems biology approaches based on next generation 'omics' technologies are now able to describe the gut microbiome at a detailed genetic and functional (transcriptomic, proteomic and metabolic) level, providing new insights into the importance of the gut microbiome in human health, and they are able to map microbiome variability between species, individuals and populations. This has established the importance of the gut microbiome in the disease pathogenesis for numerous systemic disease states, such as obesity and cardiovascular disease, and in intestinal conditions, such as inflammatory bowel disease. Thus, understanding microbiome activity is essential to the development of future personalized strategies of healthcare, as well as potentially providing new targets for drug development. Here, we review recent metagenomic and metabonomic approaches that have enabled advances in understanding gut microbiome activity in relation to human health, and gut microbial modulation for the treatment of disease. We also describe possible avenues of research in this rapidly growing field with respect to future personalized healthcare strategies. PMID:21392406

  17. 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. PMID:26302254

  18. 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

  19. 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

  20. 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

  1. Identification and Characterization of a Novel Host-Toxin Interaction in the Wheat - Stagonospora Nodorum Pathosystem

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stagonospora nodorum, casual agent of Stagonospora nodorum blotch (SNB) of wheat, produces a number of host-selective toxins (HSTs) known to be important in disease. To date, four HSTs and corresponding host sensitivity genes have been reported, and all four host-toxin interactions are significant f...

  2. 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

  3. Interactions of seedborne bacterial pathogens with host and non-host plants in relation to seed infestation and seedling transmission.

    PubMed

    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 × 10(6) 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 by

  4. Influence of symbiotic bacteria on entomopathogenic nematode--host interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are three players in the infection process of entomopathogenic nematodes (Steinernematidae and Heterorhabditidae): the nematodes themselves, the host insect, and the nematode’s mutualistic bacteria (Xenorhabdus and Photorhabdus spp.). As a host infection progresses, all three of these players...

  5. 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

  6. Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster

    PubMed Central

    Dobson, Adam J.; Chaston, John M.; Newell, Peter D.; Donahue, Leanne; Hermann, Sara L.; Sannino, David R.; Westmiller, Stephanie; Wong, Adam C.-N.; Clark, Andrew G.; Lazzaro, Brian P.; Douglas, Angela E.

    2015-01-01

    Animals bear communities of gut microorganisms with substantial effects on animal nutrition, but the host genetic basis of these effects is unknown. Here, we use Drosophila to demonstrate substantial among-genotype variation in the effects of eliminating the gut microbiota on five host nutritional indices (weight, and protein, lipid, glucose and glycogen contents); this includes variation in both the magnitude and direction of microbiota-dependent effects. Genome-wide associations to identify the genetic basis of the microbiota-dependent variation reveal polymorphisms in largely non-overlapping sets of genes associated with variation in the nutritional traits, including strong representation of conserved genes functioning in signaling. Key genes identified by the GWA study are validated by loss-of-function mutations that altered microbiota-dependent nutritional effects. We conclude that the microbiota interacts with the animal at multiple points in the signaling and regulatory networks that determine animal nutrition. These interactions with the microbiota are likely conserved across animals, including humans. PMID:25692519

  7. 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. PMID:27240978

  8. 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

  9. 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

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

    PubMed

    Abou Chakra, Maria; Hilbe, Christian; Traulsen, Arne

    2016-05-01

    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. 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

  12. Bacterial-induced cell reprogramming to stem cell-like cells: new premise in host-pathogen interactions

    PubMed Central

    Hess, Samuel; Rambukkana, Anura

    2015-01-01

    Bacterial pathogens employ a myriad of strategies to alter host tissue cell functions for bacterial advantage during infection. Recent advances revealed a fusion of infection biology with stem cell biology by demonstrating developmental reprogramming of lineage committed host glial cells to progenitor/stem cell-like cells by an intracellular bacterial pathogen Mycobacterium leprae. Acquisition of migratory and immunomodulatory properties of such reprogrammed cells provides an added advantage for promoting bacterial spread. This presents a previously unseen sophistication of cell manipulation by hijacking the genomic plasticity of host cells by a human bacterial pathogen. The rationale for such extreme fate conversion of host cells may be directly linked to the exceedingly passive obligate life style of M. leprae with a degraded genome and host cell dependence for both bacterial survival and dissemination, particularly the use of host-derived stem cell-like cells as a vehicle for spreading infection without being detected by immune cells. Thus, this unexpected link between cell reprogramming and infection opens up a new premise in host-pathogen interactions. Furthermore, such bacterial ingenuity could also be harnessed for developing natural ways of reprogramming host cells for repairing damaged tissues from infection, injury and diseases. PMID:25541240

  13. 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

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

    PubMed Central

    Memišević, Vesna; Zavaljevski, Nela; Rajagopala, Seesandra V.; Kwon, Keehwan; Pieper, Rembert; DeShazer, David; Reifman, Jaques; Wallqvist, Anders

    2015-01-01

    Burkholderia pathogenicity relies on protein virulence factors to control and promote bacterial internalization, survival, and replication within eukaryotic host cells. We recently used yeast two-hybrid (Y2H) screening to identify a small set of novel Burkholderia proteins that were shown to attenuate disease progression in an aerosol infection animal model using the virulent Burkholderia mallei ATCC 23344 strain. Here, we performed an extended analysis of primarily nine B. mallei virulence factors and their interactions with human proteins to map out how the bacteria can influence and alter host processes and pathways. Specifically, we employed topological analyses to assess the connectivity patterns of targeted host proteins, identify modules of pathogen-interacting host proteins linked to processes promoting infectivity, and evaluate the effect of crosstalk among the identified host protein modules. Overall, our analysis showed that the targeted host proteins generally had a large number of interacting partners and interacted with other host proteins that were also targeted by B. mallei proteins. We also introduced a novel Host-Pathogen Interaction Alignment (HPIA) algorithm and used it to explore similarities between host-pathogen interactions of B. mallei, Yersinia pestis, and Salmonella enterica. We inferred putative roles of B. mallei proteins based on the roles of their aligned Y. pestis and S. enterica partners and showed that up to 73% of the predicted roles matched existing annotations. A key insight into Burkholderia pathogenicity derived from these analyses of Y2H host-pathogen interactions is the identification of eukaryotic-specific targeted cellular mechanisms, including the ubiquitination degradation system and the use of the focal adhesion pathway as a fulcrum for transmitting mechanical forces and regulatory signals. This provides the mechanisms to modulate and adapt the host-cell environment for the successful establishment of host infections

  16. Interaction between viral RNA silencing suppressors and host factors in plant immunity.

    PubMed

    Nakahara, Kenji S; Masuta, Chikara

    2014-08-01

    To elucidate events in the molecular arms race between the host and pathogen in evaluating plant immunity, a zigzag model is useful for uncovering aspects common to different host-pathogen interactions. By analogy of the steps in virus-host interactions with the steps in the standard zigzag model outlined in recent papers, we may regard RNA silencing as pattern-triggered immunity (PTI) against viruses, RNA silencing suppressors (RSSs) as effectors to overcome host RNA silencing and resistance gene (R-gene)-mediated defense as effector-triggered immunity (ETI) recognizing RSSs as avirulence proteins. However, because the standard zigzag model does not fully apply to some unique aspects in the interactions between a plant host and virus, we here defined a model especially designed for viruses. Although we simplified the phenomena involved in the virus-host interactions in the model, certain specific interactive steps can be explained by integrating additional host factors into the model. These host factors are thought to play an important role in maintaining the efficacy of the various steps in the main pathway of defense against viruses in this model for virus-plant interactions. For example, we propose candidates that may interact with viral RSSs to induce the resistance response. PMID:24875766

  17. A three-way perspective of stoichiometric changes on host-parasite interactions.

    PubMed

    Aalto, Sanni L; Decaestecker, Ellen; Pulkkinen, Katja

    2015-07-01

    Changes in environmental nutrients play a crucial role in driving disease dynamics, but global patterns in nutrient-driven changes in disease are difficult to predict. In this paper we use ecological stoichiometry as a framework to review host-parasite interactions under changing nutrient ratios, focusing on three pathways: (i) altered host resistance and parasite virulence through host stoichiometry (ii) changed encounter or contact rates at population level, and (iii) changed host community structure. We predict that the outcome of nutrient changes on host-parasite interactions depends on which pathways are modified, and suggest that the outcome of infection could depend on the overlap in stoichiometric requirements of the host and the parasite. We hypothesize that environmental nutrient enrichment alters infectivity dynamics leading to fluctuating selection dynamics in host-parasite coevolution. PMID:25978937

  18. 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. PMID:24266357

  19. Infectious Bursal Disease: a complex host-pathogen interaction.

    PubMed

    Ingrao, Fiona; Rauw, Fabienne; Lambrecht, Bénédicte; van den Berg, Thierry

    2013-11-01

    Infectious Bursal Disease (IBD) is caused by a small, non-enveloped virus, highly resistant in the outside environment. Infectious Bursal Disease Virus (IBDV) targets the chicken's immune system in a very comprehensive and complex manner by destroying B lymphocytes, attracting T cells and activating macrophages. As an RNA virus, IBDV has a high mutation rate and may thus give rise to viruses with a modified antigenicity or increased virulence, as emphasized during the last decades. The molecular basis of pathogenicity and the exact cause of clinical disease and death are still poorly understood, as it is not clearly related to the severity of the lesions and the extent of the bursal damage. Recent works however, pointed out the role of an exacerbated innate immune response during the early stage of the infection with upregulated production of promediators that will induce a cytokine storm. In the case of IBDV, immunosuppression is both a direct consequence of the infection of specific target immune cells and an indirect consequence of the interactions occurring in the immune network of the host. Recovery from disease or subclinical infection will be followed by immunosuppression with more serious consequences if the strain is very virulent and infection occurs early in life. Although the immunosuppression caused by IBDV is principally directed towards B-lymphocytes, an effect on cell-mediated immunity (CMI) has also been demonstrated therefore increasing the impact of IBDV on the immunocompetence of the chicken. In addition to its zootechnical impact and its role in the development of secondary infections, it may affect the immune response of the chicken to subsequent vaccinations, essential in all types of intensive farming. Recent progress in the field of avian immunology has allowed a better knowledge of the immunological mechanisms involved in the disease but also should give improved tools for the measurement of immunosuppression in the field situation

  20. 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

  1. Bayesian species delimitation reveals generalist and specialist parasitic wasps on Galerucella beetles (Chrysomelidae): sorting by herbivore or plant host

    PubMed Central

    2013-01-01

    Background To understand the ecological and evolutionary consequences of species interactions in food webs necessitates that interactions are properly identified. Genetic analyses suggest that many supposedly generalist parasitoid species should rather be defined as multiple species with a more narrow diet, reducing the probability that such species may mediate indirect interactions such as apparent competition among hosts. Recent studies showed that the parasitoid Asecodes lucens mediate apparent competition between two hosts, Galerucella tenella and G. calmariensis, affecting both interaction strengths and evolutionary feedbacks. The same parasitoid was also recorded from other species in the genus Galerucella, suggesting that similar indirect effects may also occur for other species pairs. Methods To explore the possibility of such interactions, we sequenced mitochondrial and nuclear genetic markers to resolve the phylogeny of both host and parasitoid and to test the number of parasitoid species involved. We thus collected 139 Galerucella larvae from 8 host plant species and sequenced 31 adult beetle and 108 parasitoid individuals. Results The analysis of the Galerucella data, that also included sequences from previous studies, verified the five species previously documented as reciprocally monophyletic, but the Bayesian species delimitation for A. lucens suggested 3–4 cryptic taxa with a more specialised host use than previously suggested. The gene data analyzed under the multispecies coalescent model allowed us to reconstruct the species tree phylogeny for both host and parasitoid and we found a fully congruent coevolutionary pattern suggesting that parasitoid speciation followed upon host speciation. Conclusion Using multilocus sequence data in a Bayesian species delimitation analysis we propose that hymenopteran parasitoids of the genus Asecodes that infest Galerucella larvae constitute at least three species with narrow diet breath. The evolution of

  2. Proteomics in the investigation of HIV-1 interactions with host proteins

    PubMed Central

    Li, Ming

    2015-01-01

    Productive HIV-1 infection depends on host machinery, including a broad array of cellular proteins. Proteomics has played a significant role in the discovery of HIV-1 host proteins. In this review, after a brief survey of the HIV-1 host proteins that were discovered by proteomic analyses, we focus on analyzing the interactions between the virion and host proteins, as well as the technologies and strategies used in those proteomic studies. With the help of proteomics, the identification and characterization of HIV-1 host proteins can be translated into novel antiretroviral therapeutics. PMID:25523935

  3. HIV-Host Interactions: Implications for Vaccine Design

    PubMed Central

    Haynes, Barton F.; Shaw, George M.; Korber, Bette; Kelsoe, Garnett; Sodroski, Joseph; Hahn, Beatrice H.; Borrow, Persephone; McMichael, Andrew J.

    2016-01-01

    Summary Development of an effective AIDS vaccine is a global priority. However, the extreme diversity of human immunodeficiency virus type 1 (HIV-1), which is a consequence of its propensity to mutate to escape immune responses, along with host factors that prevent the elicitation of protective immune responses, continue to hinder vaccine development. Breakthroughs in understanding of the biology of the transmitted virus, the structure and nature of its envelope trimer, vaccine-induced CD8 T cell control in primates, and host control of broadly neutralizing antibody elicitation have given rise to new vaccine strategies. Despite this promise, emerging data from preclinical trials reinforce the need for gaining additional insight into virus – host biology in order to facilitate the development of a successful vaccine. PMID:26922989

  4. 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

  5. Antagonistic within-host interactions between plant viruses: molecular basis and impact on viral and host fitness.

    PubMed

    Syller, Jerzy; Grupa, Anna

    2016-06-01

    Double infections of related or unrelated viruses frequently occur in single plants, the viral agents being inoculated into the host plant simultaneously (co-infection) or sequentially (super-infection). Plants attacked by viruses activate sophisticated defence pathways which operate at different levels, often at significant fitness costs, resulting in yield reduction in crop plants. The occurrence and severity of the negative effects depend on the type of within-host interaction between the infecting viruses. Unrelated viruses generally interact with each other in a synergistic manner, whereas interactions between related viruses are mostly antagonistic. These can incur substantial fitness costs to one or both of the competitors. A relatively well-known antagonistic interaction is cross-protection, also referred to as super-infection exclusion. This type of interaction occurs when a previous infection with one virus prevents or interferes with subsequent infection by a homologous second virus. The current knowledge on why and how one virus variant excludes or restricts another is scant. Super-infection exclusion between viruses has predominantly been attributed to the induction of RNA silencing, which is a major antiviral defence mechanism in plants. There are, however, presumptions that various mechanisms are involved in this phenomenon. This review outlines the current state of knowledge concerning the molecular mechanisms behind antagonistic interactions between plant viruses. Harmful or beneficial effects of these interactions on viral and host plant fitness are also characterized. Moreover, the review briefly outlines the past and present attempts to utilize antagonistic interactions among viruses to protect crop plants against destructive diseases. PMID:26416204

  6. Lipids at the interface of virus-host interactions

    PubMed Central

    Chukkapalli, Vineela; Heaton, Nicholas S.; Randall, Glenn

    2012-01-01

    Viruses physically and metabolically remodel the host cell to establish an optimal environment for their replication. Many of these processes involve the manipulation of lipid signaling, synthesis and metabolism. An emerging theme is that these lipid-modifying pathways are also linked to innate anti-viral responses and can be modulated to inhibit viral replication. PMID:22682978

  7. Comparative metagenomic analyses reveal viral-induced shifts of host metabolism towards nucleotide biosynthesis

    PubMed Central

    2014-01-01

    Background Viral genomes often contain metabolic genes that were acquired from host genomes (auxiliary genes). It is assumed that these genes are fixed in viral genomes as a result of a selective force, favoring viruses that acquire specific metabolic functions. While many individual auxiliary genes were observed in viral genomes and metagenomes, there is great importance in investigating the abundance of auxiliary genes and metabolic functions in the marine environment towards a better understanding of their role in promoting viral reproduction. Results In this study, we searched for enriched viral auxiliary genes and mapped them to metabolic pathways. To initially identify enriched auxiliary genes, we analyzed metagenomic microbial reads from the Global Ocean Survey (GOS) dataset that were characterized as viral, as well as marine virome and microbiome datasets from the Line Islands. Viral-enriched genes were mapped to a “global metabolism network” that comprises all KEGG metabolic pathways. Our analysis of the viral-enriched pathways revealed that purine and pyrimidine metabolism pathways are among the most enriched pathways. Moreover, many other viral-enriched metabolic pathways were found to be closely associated with the purine and pyrimidine metabolism pathways. Furthermore, we observed that sequential reactions are promoted in pathways having a high proportion of enriched genes. In addition, these enriched genes were found to be of modular nature, participating in several pathways. Conclusions Our naïve metagenomic analyses strongly support the well-established notion that viral auxiliary genes promote viral replication via both degradation of host DNA and RNA as well as a shift of the host metabolism towards nucleotide biosynthesis, clearly indicating that comparative metagenomics can be used to understand different environments and systems without prior knowledge of pathways involved. PMID:24666644

  8. Curtovirus-cucurbit interaction: acquisition host plays a role in leafhopper transmission in a host-dependent manner.

    PubMed

    Chen, Li-Fang; Gilbertson, Robert L

    2009-01-01

    Curly top disease (CTD) of vegetable crops is caused by viruses in the genus Curtovirus (family Geminiviridae). Cucurbits are reported to be susceptible to CTD; however, the disease is rare in California despite annual outbreaks in other hosts (e.g., common bean, pepper, sugar beet, and tomato). Consistent with these observations, no obvious curly top symptoms were observed in melon fields surveyed for CTD in Central California in 2004 and 2005, whereas the disease was readily observed in tomato plants in nearby fields. However, samples of cucurbits from Idaho with curly top-like symptoms, collected in 2005 and 2007, were confirmed to have the disease. The susceptibility of cucurbits (cantaloupe, honeydew melon, pumpkin, and watermelon) to the three curtoviruses known to occur in California (Beet curly top virus, BCTV; Beet severe curly top virus, BSCTV; and Beet mild curly top virus, BMCTV) was evaluated by agroinoculation or leafhopper transmission. Irrespective of the curtovirus species and inoculation method, low rates of infection and mild or symptomless disease phenotypes were observed in cucurbits. In contrast, all inoculated tomato, Nicotiana benthamiana, or shepherd's purse plants were infected and developed severe symptoms. In leafhopper transmission experiments, BMCTV infected cucurbits when leafhoppers acquired the virus from a symptomatic host with a high viral titer (shepherd's purse), whereas no infection occurred when the acquisition host had mild symptoms and a low viral titer (sugar beet); in contrast, the acquisition host did not influence transmission of BMCTV to tomato or shepherd's purse (all plants were infected). This revealed an influence of the acquisition host on leafhopper transmission in a host-specific manner. Our results also indicate that, although cucurbits can develop CTD, they are relatively poor hosts for these curtoviruses. PMID:19055441

  9. 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

    2016-01-01

    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

  10. 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

  11. Comparative Pathogenomics Reveals Horizontally Acquired Novel Virulence Genes in Fungi Infecting Cereal Hosts

    PubMed Central

    Gardiner, Donald M.; McDonald, Megan C.; Covarelli, Lorenzo; Solomon, Peter S.; Rusu, Anca G.; Marshall, Mhairi; Kazan, Kemal; Chakraborty, Sukumar; McDonald, Bruce A.; Manners, John M.

    2012-01-01

    Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens. PMID:23028337

  12. Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions

    PubMed Central

    Zhong, Yanxin; Tan, Yong Wah; Liu, Ding Xiang

    2012-01-01

    Animal coronaviruses, such as infectious bronchitis virus (IBV), and arteriviruses, such as porcine reproductive and respiratory syndrome virus (PRRSV), are able to manifest highly contagious infections in their specific native hosts, thereby arising in critical economic damage to animal industries. This review discusses recent progress in studies of virus-host interactions during animal and human coronavirus and arterivirus infections, with emphasis on IBV-host cell interactions. These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. PMID:22816036

  13. 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. PMID:25085536

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

    PubMed Central

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

    2015-01-01

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

  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. Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

    PubMed Central

    Costales, Jaime A; Daily, Johanna P; Burleigh, Barbara A

    2009-01-01

    Background The requirements for growth and survival of the intracellular pathogen Trypanosoma cruzi within mammalian host cells are poorly understood. Transcriptional profiling of the host cell response to infection serves as a rapid read-out for perturbation of host physiology that, in part, reflects adaptation to the infective process. Using Affymetrix oligonucleotide array analysis we identified common and disparate host cell responses triggered by T. cruzi infection of phenotypically diverse human cell types. Results We report significant changes in transcript abundance in T. cruzi-infected fibroblasts, endothelial cells and smooth muscle cells (2852, 2155 and 531 genes respectively; fold-change ≥ 2, p-value < 0.01) 24 hours post-invasion. A prominent type I interferon response was observed in each cell type, reflecting a secondary response to secreted cytokine in infected cultures. To identify a core cytokine-independent response in T. cruzi-infected fibroblasts and endothelial cells transwell plates were used to distinguish cytokine-dependent and -independent gene expression profiles. This approach revealed the induction of metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding as common themes in T. cruzi-infected cells. In addition, the downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection may impede host cell cycle progression. The observation of impaired cytokinesis in T. cruzi-infected cells, following nuclear replication, confirmed this prediction. Conclusion Metabolic pathways and cellular processes were identified as significantly altered at the transcriptional level in response to T. cruzi infection in a cytokine-independent manner. Several of these alterations are supported by previous studies of T. cruzi metabolic requirements or effects on the host. However, our methods also revealed a T. cruzi-dependent block in the host cell cycle, at

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

    SciTech Connect

    Truong, Thai Viet

    2005-12-20

    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.

  18. 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

  19. Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts

    PubMed Central

    Doolittle, Janet M.; Gomez, Shawn M.

    2011-01-01

    Background Dengue fever is an increasingly significant arthropod-borne viral disease, with at least 50 million cases per year worldwide. As with other viral pathogens, dengue virus is dependent on its host to perform the bulk of functions necessary for viral survival and replication. To be successful, dengue must manipulate host cell biological processes towards its own ends, while avoiding elimination by the immune system. Protein-protein interactions between the virus and its host are one avenue through which dengue can connect and exploit these host cellular pathways and processes. Methodology/Principal Findings We implemented a computational approach to predict interactions between Dengue virus (DENV) and both of its hosts, Homo sapiens and the insect vector Aedes aegypti. Our approach is based on structural similarity between DENV and host proteins and incorporates knowledge from the literature to further support a subset of the predictions. We predict over 4,000 interactions between DENV and humans, as well as 176 interactions between DENV and A. aegypti. Additional filtering based on shared Gene Ontology cellular component annotation reduced the number of predictions to approximately 2,000 for humans and 18 for A. aegypti. Of 19 experimentally validated interactions between DENV and humans extracted from the literature, this method was able to predict nearly half (9). Additional predictions suggest specific interactions between virus and host proteins relevant to interferon signaling, transcriptional regulation, stress, and the unfolded protein response. Conclusions/Significance Dengue virus manipulates cellular processes to its advantage through specific interactions with the host's protein interaction network. The interaction networks presented here provide a set of hypothesis for further experimental investigation into the DENV life cycle as well as potential therapeutic targets. PMID:21358811

  20. A hyperbranched supramolecular polymer constructed by orthogonal triple hydrogen bonding and host-guest interactions.

    PubMed

    Gu, Ruirui; Yao, Jian; Fu, Xin; Zhou, Wei; Qu, Da-Hui

    2015-03-28

    A hyperbranched supramolecular polymer has been constructed through orthogonal self-crosslinking by two classical binding interactions: triple hydrogen bonding interaction between a three-arm melamine derivative and DB24C8-containing bisimide and host-guest interaction between DB24C8 crown ether and ditopic dibenzyl ammonium moieties. PMID:25421931

  1. Host-virus interaction: a new role for microRNAs

    PubMed Central

    Scaria, Vinod; Hariharan, Manoj; Maiti, Souvik; Pillai, Beena; Brahmachari, Samir K

    2006-01-01

    MicroRNAs (miRNAs) are a new class of 18–23 nucleotide long non-coding RNAs that play critical roles in a wide spectrum of biological processes. Recent reports also throw light into the role of microRNAs as critical effectors in the intricate host-pathogen interaction networks. Evidence suggests that both virus and hosts encode microRNAs. The exclusive dependence of viruses on the host cellular machinery for their propagation and survival also make them highly susceptible to the vagaries of the cellular environment like small RNA mediated interference. It also gives the virus an opportunity to fight and/or modulate the host to suite its needs. Thus the range of interactions possible through miRNA-mRNA cross-talk at the host-pathogen interface is large. These interactions can be further fine-tuned in the host by changes in gene expression, mutations and polymorphisms. In the pathogen, the high rate of mutations adds to the complexity of the interaction network. Though evidence regarding microRNA mediated cross-talk in viral infections is just emerging, it offers an immense opportunity not only to understand the intricacies of host-pathogen interactions, and possible explanations to viral tropism, latency and oncogenesis, but also to develop novel biomarkers and therapeutics. PMID:17032463

  2. Molecular biology of viroid-host interactions and disease control strategies.

    PubMed

    Kovalskaya, Natalia; Hammond, Rosemarie W

    2014-11-01

    Viroids are single-stranded, covalently closed, circular, highly structured noncoding RNAs that cause disease in several economically important crop plants. They replicate autonomously and move systemically in host plants with the aid of the host machinery. In addition to symptomatic infections, viroids also cause latent infections where there is no visual evidence of infection in the host; however, transfer to a susceptible host can result in devastating disease. While there are non-hosts for viroids, no naturally occurring durable resistance has been observed in most host species. Current effective control methods for viroid diseases include detection and eradication, and cultural controls. In addition, heat or cold therapy combined with meristem tip culture has been shown to be effective for elimination of viroids for some viroid-host combinations. An understanding of viroid-host interactions, host susceptibility, and non-host resistance could provide guidance for the design of viroid-resistant plants. Efforts to engineer viroid resistance into host species have been underway for several years, and include the use of antisense RNA, antisense RNA plus ribozymes, a dsRNase, and siRNAs, among others. The results of those efforts and the challenges associated with creating viroid resistant plants are summarized in this review. PMID:25438785

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

    PubMed

    Stappenbeck, Thaddeus S; Virgin, Herbert W

    2016-06-01

    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. PMID:27279212

  4. 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. PMID:25156651

  5. Global approaches to study protein-protein interactions among viruses and hosts.

    PubMed

    Mendez-Rios, Jorge; Uetz, Peter

    2010-02-01

    While high-throughput protein-protein interaction screens were first published approximately 10 years ago, systematic attempts to map interactions among viruses and hosts started only a few years ago. HIV-human interactions dominate host-pathogen interaction databases (with approximately 2000 interactions) despite the fact that probably none of these interactions have been identified in systematic interaction screens. Recently, combinations of protein interaction data with RNAi and other functional genomics data allowed researchers to model more complex interaction networks. The rapid progress in this area promises a flood of new data in the near future, with clinical applications as soon as structural and functional genomics catches up with next-generation sequencing of human variation and structure-based drug design. PMID:20143950

  6. 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.

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

    PubMed Central

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

    2010-01-01

    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 Å, 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. PMID:20089642

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

    PubMed Central

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

    2014-01-01

    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. PMID:24973749

  9. Host-pathogen interactions in urinary tract infection.

    PubMed

    Nielubowicz, Greta R; Mobley, Harry L T

    2010-08-01

    The urinary tract is a common site of bacterial infections; nearly half of all women experience at least one urinary tract infection (UTI) during their lifetime. These infections are classified based on the condition of the host. Uncomplicated infections affect otherwise healthy individuals and are most commonly caused by uropathogenic Escherichia coli, whereas complicated infections affect patients with underlying difficulties, such as a urinary tract abnormality or catheterization, and are commonly caused by species such as Proteus mirabilis. Virulence and fitness factors produced by both pathogens include fimbriae, toxins, flagella, iron acquisition systems, and proteins that function in immune evasion. Additional factors that contribute to infection include the formation of intracellular bacterial communities by E. coli and the production of urease by P. mirabilis, which can result in urinary stone formation. Innate immune responses are induced or mediated by pattern recognition receptors, antimicrobial peptides, and neutrophils. The adaptive immune response to UTI is less well understood. Host factors TLR4 and CXCR1 are implicated in disease outcome and susceptibility, respectively. Low levels of TLR4 are associated with asymptomatic bacteriuria while low levels of CXCR1 are associated with increased incidence of acute pyelonephritis. Current research is focused on the identification of additional virulence factors and therapeutic or prophylactic targets that might be used in the generation of vaccines against both uropathogens. PMID:20647992

  10. 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

  11. Evolution of Hawaiian shield volcano revealed by antecryst-hosted melt inclusions

    NASA Astrophysics Data System (ADS)

    Tanaka, R.; Sakyi, P. A.; Kobayashi, K.; Nakamura, E.

    2009-12-01

    Ocean island basalts, exemplified by the Hawaiian Volcanics, are often considered to be the best targets for understanding the chemical and thermal structure of upwelling mantle plumes. The important feature with regards to the petrogenesis of the recent Hawaiian shield building lavas is the existence of a double volcanic loci (Loa and Kea), which has resulted in large-scale heterogeneity between the north-western and south-eastern sides of the plume. The temporal Sr-Nd-Hf-Pb isotopic trends displayed by the Loa-type lavas may have been caused by systematic vertical heterogeneity of the SW part of the Hawaiian plume. The majority of the available OIB samples are limited to the youngest lava flows covering the shield, with the exception of samples obtained from drilled cores and land slide deposits. Thus, sampling is biased to the latest stages of the shield building process, and consequently, so are geochemical studies. We found that the majority of olivine crystals coarser than ˜1 mm in the Hawaiian lavas are antecryst, which originally crystallized from previous stages of Hawaiian magmatism. These anatecrysts were then plastically deformed prior to entrainment in the erupted host magmas. The Pb isotopic compositions of antecryst-hosted melt inclusions reveal that the mantle source components that formed Hawaiian shields successively changed during shield formation. The temporal geochemical trend in the Kilauea melt inclusion could be caused by increasing the degree of partial melting by moving the melting source of the volcano from the periphery to the centre of the plume. The Pb isotopic trend of Koolau melt inclusions are consistent with the previously identified temporal isotopic trend, which shows that the 207Pb/206Pb and 208Pb/206Pb of the Koolau magma systematically increased with time. Thus, antecryst-hosted melt inclusions preserve geochemical information regarding the petrogenesis of the Hawaiian shield lavas, which is unobtainable via whole rock

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

    PubMed

    Bannister, L H

    1979-04-11

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

  13. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners.

    PubMed

    Barnoud, Thibaut; Wilkey, Daniel W; Merchant, Michael L; Clark, Jennifer A; Donninger, Howard

    2016-01-01

    RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K-Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated. PMID:26999212

  14. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners

    PubMed Central

    Barnoud, Thibaut; Wilkey, Daniel W.; Merchant, Michael L.; Clark, Jennifer A.; Donninger, Howard

    2016-01-01

    RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K-Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated. PMID:26999212

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

    PubMed

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

    2012-09-01

    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 suggesting genetic basis for

  16. 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

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

    PubMed

    Dong, Xiaonan; Feng, Pinghui

    2011-01-01

    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

  18. Microbiota-Host Interactions in Mucosal Homeostasis and Systemic Autoimmunity

    PubMed Central

    Longman, Randy S.; Yang, Yi; Diehl, Gretchen E.; Kim, Sangwon V.; Littman, Dan R.

    2015-01-01

    The vertebrate intestinal tract is colonized by hundreds of species of bacteria that must be compartmentalized and tolerated to prevent invasive growth and harmful inflammatory responses. Signaling initiated by commensal bacteria shapes antigen-specific mucosal and systemic adaptive immunity. A distinct type of effector CD4+ T cells, Th17 cells, play a key role in coordinating the inflammatory immune responses that afford protection to pathogens at the mucosal interface. Balancing this powerful inflammatory response, regulatory T cells limit collateral damage and provide antigen-specific tolerance to both food and microbial antigens. Here, we discuss the implications for how the microbiota as a whole contribute to compartmentalization from the host and how individual constituents of the microbiota influence the functions and repertoire of effector T cells and organ-specific autoimmune disease. PMID:24913313

  19. 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. PMID:25208092

  20. 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 Central

    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. PMID:25208092

  1. 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

  2. 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. PMID:26990415

  3. Ehrlichia chaffeensis TRP32 Interacts with Host Cell Targets That Influence Intracellular Survival

    PubMed Central

    Luo, Tian

    2012-01-01

    Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes and survives by evading host cell defense mechanisms. Recently, molecular interactions of E. chaffeensis tandem repeat proteins 47 and 120 (TRP47 and -120) and the eukaryotic host cell have been described. In this investigation, yeast two-hybrid analysis demonstrated that an E. chaffeensis type 1 secretion system substrate, TRP32, interacts with a diverse group of human proteins associated with major biological processes of the host cell, including protein synthesis, trafficking, degradation, immune signaling, cell signaling, iron metabolism, and apoptosis. Eight target proteins, including translation elongation factor 1 alpha 1 (EF1A1), deleted in azoospermia (DAZ)-associated protein 2 (DAZAP2), ferritin light polypeptide (FTL), CD63, CD14, proteasome subunit beta type 1 (PSMB1), ring finger and CCCH-type domain 1 (RC3H1), and tumor protein p53-inducible protein 11 (TP53I11) interacted with TRP32 as determined by coimmunoprecipitation assays, colocalization with TRP32 in HeLa and THP-1 cells, and/or RNA interference. Interactions between TRP32 and host targets localized to the E. chaffeensis morulae or in the host cell cytoplasm adjacent to morulae. Common or closely related interacting partners of E. chaffeensis TRP32, TRP47, and TRP120 demonstrate a molecular convergence on common cellular processes and molecular cross talk between Ehrlichia TRPs and host targets. These findings further support the role of TRPs as effectors that promote intracellular survival. PMID:22547548

  4. The seven-transmembrane receptor Gpr1 governs processes relevant for the antagonistic interaction of Trichoderma atroviride with its host.

    PubMed

    Omann, Markus R; Lehner, Sylvia; Escobar Rodríguez, Carolina; Brunner, Kurt; Zeilinger, Susanne

    2012-01-01

    Mycoparasitic Trichoderma species are applied as biocontrol agents in agriculture to guard plants against fungal diseases. During mycoparasitism, Trichoderma directly interacts with phytopathogenic fungi, preceded by a specific recognition of the host and resulting in its disarming and killing. In various fungal pathogens, including mycoparasites, signalling via heterotrimeric G proteins plays a major role in regulating pathogenicity-related functions. However, the corresponding receptors involved in the recognition of host-derived signals are largely unknown. Functional characterization of Trichoderma atroviride Gpr1 revealed a prominent role of this seven-transmembrane protein of the cAMP-receptor-like family of fungal G-protein-coupled receptors in the antagonistic interaction with the host fungus and governing of mycoparasitism-related processes. Silencing of gpr1 led to an avirulent phenotype accompanied by an inability to attach to host hyphae. Furthermore, gpr1-silenced transformants were unable to respond to the presence of living host fungi with the expression of chitinase- and protease-encoding genes. Addition of exogenous cAMP was able to restore host attachment in gpr1-silenced transformants but could not restore mycoparasitic overgrowth. A search for downstream targets of the signalling pathway(s) involving Gpr1 resulted in the isolation of genes encoding e.g. a member of the cyclin-like superfamily and a small secreted cysteine-rich protein. Although silencing of gpr1 caused defects similar to those of mutants lacking the Tga3 Gα protein, no direct interaction between Gpr1 and Tga3 was observed in a split-ubiquitin two-hybrid assay. PMID:22075023

  5. Host-Symbiont Interactions: Male-Killers Exposed.

    PubMed

    Larracuente, Amanda M; Meller, Victoria H

    2016-05-23

    Male-killing is one strategy used by maternally transmitted bacterial symbionts to boost transmission and spread in populations. In Drosophila melanogaster, Spiroplasma target males by hijacking an essential, male-limited epigenetic process. A new study reveals clues to the mode of killing. PMID:27218854

  6. 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

  7. Oligosaccharide Binding Proteins from Bifidobacterium longum subsp. infantis Reveal a Preference for Host Glycans

    PubMed Central

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

    2011-01-01

    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. PMID:21423604

  8. 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

  9. 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

  10. 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.

  11. 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. PMID:27068808

  12. Metabolism and Virulence Strategies in Dickeya-Host Interactions.

    PubMed

    Hugouvieux-Cotte-Pattat, N

    2016-01-01

    Dickeya, a genus of the Enterobacteriaceae family, all cause plant diseases. They are aggressive necrotrophs that have both a wide geographic distribution and a wide host range. As a plant pathogen, Dickeya has had to adapt to a vegetarian diet. Plants constitute a large storage of carbohydrates; they contain substantial amounts of soluble sugars and the plant cell wall is composed of long polysaccharides. Metabolic functions used by Dickeya in order to multiply during infection are essential aspects of pathogenesis. Dickeya is able to catabolize a large range of oligosaccharides and glycosides of plant origin. Glucose, fructose, and sucrose are all efficiently metabolized by the bacteria. To avoid the formation of acidic products, their final catabolism involves the butanediol pathway, a nonacidifying fermentative pathway. The assimilation of plant polysaccharides necessitates their prior cleavage into oligomers. Notably, the Dickeya virulence strategy is based on its capacity to dissociate the plant cell wall and, for this, the bacteria secrete an extensive set of polysaccharide degrading enzymes, composed mostly of pectinases. Since pectic polymers have a major role in plant tissue cohesion, pectinase action results in plant rot. The pectate lyases secreted by Dickeya play a double role as virulence factors and as nutrient providers. This dual function implies that the pel gene expression is regulated by both metabolic and virulence regulators. The control of sugar assimilation by specific or global regulators enables Dickeya to link its nutritional status to virulence, a coupling that optimizes the different phases of infection. PMID:27571693

  13. Development of viable TAP-tagged dengue virus for investigation of host-virus interactions in viral replication.

    PubMed

    Poyomtip, Teera; Hodge, Kenneth; Matangkasombut, Ponpan; Sakuntabhai, Anavaj; Pisitkun, Trairak; Jirawatnotai, Siwanon; Chimnaronk, Sarin

    2016-03-01

    Dengue virus (DENV) is a mosquito-borne flavivirus responsible for life-threatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The viral replication machinery containing the core non-structural protein 5 (NS5) is implicated in severe dengue symptoms but molecular details remain obscure. To date, studies seeking to catalogue and characterize interaction networks between viral NS5 and host proteins have been limited to the yeast two-hybrid system, computational prediction and co-immunoprecipitation (IP) of ectopically expressed NS5. However, these traditional approaches do not reproduce a natural course of infection in which a number of DENV NS proteins colocalize and tightly associate during the replication process. Here, we demonstrate the development of a recombinant DENV that harbours a TAP tag in NS5 to study host-virus interactions in vivo. We show that our engineered DENV was infective in several human cell lines and that the tags were stable over multiple viral passages, suggesting negligible structural and functional disturbance of NS5. We further provide proof-of-concept for the use of rationally tagged virus by revealing a high confidence NS5 interaction network in human hepatic cells. Our analysis uncovered previously unrecognized hnRNP complexes and several low-abundance fatty acid metabolism genes, which have been implicated in the viral life cycle. This study sets a new standard for investigation of host-flavivirus interactions. PMID:26669909

  14. 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. PMID:26470292

  15. 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

  16. 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

  17. A walk on the tundra: Host-parasite interactions in an extreme environment.

    PubMed

    Kutz, Susan J; Hoberg, Eric P; Molnár, Péter K; Dobson, Andy; Verocai, Guilherme G

    2014-08-01

    Climate change is occurring very rapidly in the Arctic, and the processes that have taken millions of years to evolve in this very extreme environment are now changing on timescales as short as decades. These changes are dramatic, subtle and non-linear. In this article, we discuss the evolving insights into host-parasite interactions for wild ungulate species, specifically, muskoxen and caribou, in the North American Arctic. These interactions occur in an environment that is characterized by extremes in temperature, high seasonality, and low host species abundance and diversity. We believe that lessons learned in this system can guide wildlife management and conservation throughout the Arctic, and can also be generalized to more broadly understand host-parasite interactions elsewhere. We specifically examine the impacts of climate change on host-parasite interactions and focus on: (I) the direct temperature effects on parasites; (II) the importance of considering the intricacies of host and parasite ecology for anticipating climate change impacts; and (III) the effect of shifting ecological barriers and corridors. Insights gained from studying the history and ecology of host-parasite systems in the Arctic will be central to understanding the role that climate change is playing in these more complex systems. PMID:25180164

  18. Viral-Host Protein Interaction Studies Using Yeast Two-Hybrid Screening Method.

    PubMed

    Dudha, Namrata; Gupta, Sanjay

    2016-01-01

    Yeast two-hybrid (Y2H) assay is one of the earliest methods developed to study protein-protein interactions. In the proteomics era, Y2H has created a niche of its own by providing protein interaction maps for various organisms. Owing to limited coding capacities of their genomes, viruses are dependent on their host cellular machinery for successful infection. Identification of the key players orchestrating the survival of virus in their host is essential for understanding viral life cycle and devising strategies to prevent interactions resulting in pathogenesis. In this chapter, Y2H assay will be explained in detail for studying viral-host protein interactions of Chikungunya virus (CHIKV). PMID:27233270

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

    PubMed

    Warrick, Jay W; Timm, Andrea; 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

  20. 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

  1. 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

  2. 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. PMID:25848871

  3. Synthetic protein interactions reveal a functional map of the cell

    PubMed Central

    Berry, Lisa K; Ólafsson, Guðjón; Ledesma-Fernández, Elena; Thorpe, Peter H

    2016-01-01

    To understand the function of eukaryotic cells, it is critical to understand the role of protein-protein interactions and protein localization. Currently, we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations – a key requirement for the evolution of new protein functions. To answer this question, we fused every protein in the yeast Saccharomyces cerevisiae with a partner from each of the major cellular compartments and quantitatively assessed the effects upon growth. This analysis reveals that cells have a remarkable and unanticipated tolerance for forced protein associations, even if these associations lead to a proportion of the protein moving compartments within the cell. Furthermore, the interactions that do perturb growth provide a functional map of spatial protein regulation, identifying key regulatory complexes for the normal homeostasis of eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.13053.001 PMID:27098839

  4. Identification of Proteins Bound to Dengue Viral RNA In Vivo Reveals New Host Proteins Important for Virus Replication

    PubMed Central

    Phillips, Stacia L.; Soderblom, Erik J.

    2016-01-01

    ABSTRACT Dengue virus is the most prevalent cause of arthropod-borne infection worldwide. Due to the limited coding capacity of the viral genome and the complexity of the viral life cycle, host cell proteins play essential roles throughout the course of viral infection. Host RNA-binding proteins mediate various aspects of virus replication through their physical interactions with viral RNA. Here we describe a technique designed to identify such interactions in the context of infected cells using UV cross-linking followed by antisense-mediated affinity purification and mass spectrometry. Using this approach, we identified interactions, several of them novel, between host proteins and dengue viral RNA in infected Huh7 cells. Most of these interactions were subsequently validated using RNA immunoprecipitation. Using small interfering RNA (siRNA)-mediated gene silencing, we showed that more than half of these host proteins are likely involved in regulating virus replication, demonstrating the utility of this method in identifying biologically relevant interactions that may not be identified using traditional in vitro approaches. PMID:26733069

  5. Simulation of climate-tick-host-landscape interactions: Effects of shifts in the seasonality of host population fluctuations on tick densities.

    PubMed

    Wang, Hsiao-Hsuan; Grant, W E; Teel, P D; Hamer, S A

    2015-12-01

    Tick vector systems are comprised of complex climate-tick-host-landscape interactions that are difficult to identify and estimate from empirical observations alone. We developed a spatially-explicit, individual-based model, parameterized to represent ecological conditions typical of the south-central United States, to examine effects of shifts in the seasonal occurrence of fluctuations of host densities on tick densities. Simulated shifts in the seasonal occurrence of periods of high and low host densities affected both the magnitude of unfed tick densities and the seasonality of tick development. When shifting the seasonal densities of all size classes of hosts (small, medium, and large) synchronously, densities of nymphs were affected more by smaller shifts away from the baseline host seasonality than were densities of larval and adult life stages. When shifting the seasonal densities of only a single size-class of hosts while holding other size classes at their baseline levels, densities of larval, nymph, and adult life stages responded differently. Shifting seasonal densities of any single host-class earlier resulted in a greater increase in adult tick density than when seasonal densities of all host classes were shifted earlier simultaneously. The mean densities of tick life stages associated with shifts in host densities resulted from system-level interactions of host availability with tick phenology. For example, shifting the seasonality of all hosts ten weeks earlier resulted in an approximately 30% increase in the relative degree of temporal co-occurrence of actively host-seeking ticks and hosts compared to baseline, whereas shifting the seasonality of all hosts ten weeks later resulted in an approximately 70% decrease compared to baseline. Differences among scenarios in the overall presence of active host-seeking ticks in the system were due primarily to the degree of co-occurrence of periods of high densities of unfed ticks and periods of high densities

  6. Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection

    PubMed Central

    Lum, Krystal K; Cristea, Ileana M

    2016-01-01

    The integration of proteomic methods to virology has facilitated a significant breadth of biological insight into mechanisms of virus replication, antiviral host responses and viral subversion of host defenses. Throughout the course of infection, these cellular mechanisms rely heavily on the formation of temporally and spatially regulated virus–host protein–protein interactions. Reviewed here are proteomic-based approaches that have been used to characterize this dynamic virus–host interplay. Specifically discussed are the contribution of integrative mass spectrometry, antibody-based affinity purification of protein complexes, cross-linking and protein array techniques for elucidating complex networks of virus–host protein associations during infection with a diverse range of RNA and DNA viruses. The benefits and limitations of applying proteomic methods to virology are explored, and the contribution of these approaches to important biological discoveries and to inspiring new tractable avenues for the design of antiviral therapeutics is highlighted. PMID:26817613

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

    PubMed

    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

  8. Insects Can Count: Sensory Basis of Host Discrimination in Parasitoid Wasps Revealed

    PubMed Central

    Ruschioni, Sara; van Loon, Joop J. A.; Smid, Hans M.; van Lenteren, Joop C.

    2015-01-01

    The solitary parasitoid Leptopilina heterotoma is one of the best studied organisms concerning the ecology, behaviour and physiology of host discrimination. Behavioural evidence shows that L. heterotoma uses its ovipositor to discriminate not only between parasitized and unparasitized Drosophila melanogaster larvae, but also to discriminate between hosts with different numbers of parasitoid eggs. The existing knowledge about how and when the parasitoid marks the host motivated us to unravel the chemosensory basis of host discrimination by L. heterotoma that allows it to choose the “best” host available. In this paper we report on electrophysiological recordings of multi-neural responses from the single taste sensillum on the tip of the unpaired ovipositor valve. We stimulated this sensillum with haemolymph of unparasitized, one-time-parasitized and two-times-parasitized Drosophila larvae. We demonstrate for the first time that quantitative characteristics of the neural responses to these haemolymph samples differed significantly, implying that host discrimination is encoded by taste receptor neurons in the multi-neuron coeloconic ovipositor sensillum. The activity of three of the six neurons present in the sensillum suffices for host discrimination and support the hypothesis that L. heterotoma females employ an ensemble code of parasitization status of the host. PMID:26466380

  9. Insects Can Count: Sensory Basis of Host Discrimination in Parasitoid Wasps Revealed.

    PubMed

    Ruschioni, Sara; van Loon, Joop J A; Smid, Hans M; van Lenteren, Joop C

    2015-01-01

    The solitary parasitoid Leptopilina heterotoma is one of the best studied organisms concerning the ecology, behaviour and physiology of host discrimination. Behavioural evidence shows that L. heterotoma uses its ovipositor to discriminate not only between parasitized and unparasitized Drosophila melanogaster larvae, but also to discriminate between hosts with different numbers of parasitoid eggs. The existing knowledge about how and when the parasitoid marks the host motivated us to unravel the chemosensory basis of host discrimination by L. heterotoma that allows it to choose the "best" host available. In this paper we report on electrophysiological recordings of multi-neural responses from the single taste sensillum on the tip of the unpaired ovipositor valve. We stimulated this sensillum with haemolymph of unparasitized, one-time-parasitized and two-times-parasitized Drosophila larvae. We demonstrate for the first time that quantitative characteristics of the neural responses to these haemolymph samples differed significantly, implying that host discrimination is encoded by taste receptor neurons in the multi-neuron coeloconic ovipositor sensillum. The activity of three of the six neurons present in the sensillum suffices for host discrimination and support the hypothesis that L. heterotoma females employ an ensemble code of parasitization status of the host. PMID:26466380

  10. Towards accurate porosity descriptors based on guest-host interactions.

    PubMed

    Paik, Dooam; Haranczyk, Maciej; Kim, Jihan

    2016-05-01

    For nanoporous materials at the characterization level, geometry-based approaches have become the methods of choice to provide information, often encoded in numerical descriptors, about the pores and the channels of a porous material. Examples of most common descriptors of the latter are pore limiting diameters, accessible surface area and accessible volume. The geometry-based methods exploit hard-sphere approximation for atoms, which (1) reduces costly computations of the interatomic interactions between the probe guest molecule and the porous material framework atoms, (2) effectively exploit applied mathematics methods such as Voronoi decomposition to represent and characterize porosity. In this work, we revisit and quantify the shortcoming of the geometry-based approaches. To do so, we have developed a series of algorithms to calculate pore descriptors such as void fraction, accessible surface area, pore limiting diameters (largest included sphere, and largest free sphere) based on a classical force field model of interactions between the guest and the framework atoms. Our resulting energy-based methods are tested on diverse sets of metal-organic frameworks and zeolite structures and comparisons against results obtained from geometric-based method indicate deviations in the cases for structures with small pore sizes. The method provides both high accuracy and performance making it suitable when screening a large database of materials. PMID:27054971

  11. Myxoma virus in the European rabbit: interactions between the virus and its susceptible host.

    PubMed

    Stanford, Marianne M; Werden, Steven J; McFadden, Grant

    2007-01-01

    Myxoma virus (MV) is a poxvirus that evolved in Sylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts. PMID:17296158

  12. The mode of host–parasite interaction shapes coevolutionary dynamics and the fate of host cooperation

    PubMed Central

    Quigley, Benjamin J. Z.; García López, Diana; Buckling, Angus; McKane, Alan J.; Brown, Sam P.

    2012-01-01

    Antagonistic coevolution between hosts and parasites can have a major impact on host population structures, and hence on the evolution of social traits. Using stochastic modelling techniques in the context of bacteria–virus interactions, we investigate the impact of coevolution across a continuum of host–parasite genetic specificity (specifically, where genotypes have the same infectivity/resistance ranges (matching alleles, MA) to highly variable ranges (gene-for-gene, GFG)) on population genetic structure, and on the social behaviour of the host. We find that host cooperation is more likely to be maintained towards the MA end of the continuum, as the more frequent bottlenecks associated with an MA-like interaction can prevent defector invasion, and can even allow migrant cooperators to invade populations of defectors. PMID:22740644

  13. Host proteins interacting with the Moloney murine leukemia virus integrase: Multiple transcriptional regulators and chromatin binding factors

    PubMed Central

    Studamire, Barbara; Goff, Stephen P

    2008-01-01

    Background A critical step for retroviral replication is the stable integration of the provirus into the genome of its host. The viral integrase protein is key in this essential step of the retroviral life cycle. Although the basic mechanism of integration by mammalian retroviruses has been well characterized, the factors determining how viral integration events are targeted to particular regions of the genome or to regions of a particular DNA structure remain poorly defined. Significant questions remain regarding the influence of host proteins on the selection of target sites, on the repair of integration intermediates, and on the efficiency of integration. Results We describe the results of a yeast two-hybrid screen using Moloney murine leukemia virus integrase as bait to screen murine cDNA libraries for host proteins that interact with the integrase. We identified 27 proteins that interacted with different integrase fusion proteins. The identified proteins include chromatin remodeling, DNA repair and transcription factors (13 proteins); translational regulation factors, helicases, splicing factors and other RNA binding proteins (10 proteins); and transporters or miscellaneous factors (4 proteins). We confirmed the interaction of these proteins with integrase by testing them in the context of other yeast strains with GAL4-DNA binding domain-integrase fusions, and by in vitro binding assays between recombinant proteins. Subsequent analyses revealed that a number of the proteins identified as Mo-MLV integrase interactors also interact with HIV-1 integrase both in yeast and in vitro. Conclusion We identify several proteins interacting directly with both MoMLV and HIV-1 integrases that may be common to the integration reaction pathways of both viruses. Many of the proteins identified in the screen are logical interaction partners for integrase, and the validity of a number of the interactions are supported by other studies. In addition, we observe that some of the

  14. 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

  15. Host-induced gene silencing: a tool for understanding fungal host interaction and for developing novel disease control strategies.

    PubMed

    Nunes, Cristiano C; Dean, Ralph A

    2012-06-01

    Recent discoveries regarding small RNAs and the mechanisms of gene silencing are providing new opportunities to explore fungal pathogen-host interactions and potential strategies for novel disease control. Plant pathogenic fungi are a constant and major threat to global food security; they represent the largest group of disease-causing agents on crop plants on the planet. An initial understanding of RNA silencing mechanisms and small RNAs was derived from model fungi. Now, new knowledge with practical implications for RNA silencing is beginning to emerge from the study of plant-fungus interactions. Recent studies have shown that the expression of silencing constructs in plants designed on fungal genes can specifically silence their targets in invading pathogenic fungi, such as Fusarium verticillioides, Blumeria graminis and Puccinia striiformis f.sp. tritici. Here, we highlight the important general aspects of RNA silencing mechanisms and emphasize recent findings from plant pathogenic fungi. Strategies to employ RNA silencing to investigate the basis of fungal pathogenesis are discussed. Finally, we address important aspects for the development of fungal-derived resistance through the expression of silencing constructs in host plants as a powerful strategy to control fungal disease. PMID:22111693

  16. Picornavirus IRES elements: RNA structure and host protein interactions.

    PubMed

    Martínez-Salas, Encarnación; Francisco-Velilla, Rosario; Fernandez-Chamorro, Javier; Lozano, Gloria; Diaz-Toledano, Rosa

    2015-08-01

    Internal ribosome entry site (IRES) elements were discovered in picornaviruses. These elements are cis-acting RNA sequences that adopt diverse three-dimensional structures and recruit the translation machinery using a 5' end-independent mechanism assisted by a subset of translation initiation factors and various RNA binding proteins termed IRES transacting factors (ITAFs). Many of these factors suffer important modifications during infection including cleavage by picornavirus proteases, changes in the phosphorylation level and/or redistribution of the protein from the nuclear to the cytoplasm compartment. Picornavirus IRES are amongst the most potent elements described so far. However, given their large diversity and complexity, the mechanistic basis of its mode of action is not yet fully understood. This review is focused to describe recent advances on the studies of RNA structure and RNA-protein interactions modulating picornavirus IRES activity. PMID:25617758

  17. 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

  18. Comparative analysis of Leishmania exoproteomes: implication for host-pathogen interactions.

    PubMed

    Peysselon, Franck; Launay, Guillaume; Lisacek, Frédérique; Duclos, Bertrand; Ricard-Blum, Sylvie

    2013-12-01

    Leishmaniasis is a vector-borne disease caused by the protozoa Leishmania. We have analyzed and compared the sequences of three experimental exoproteomes of Leishmania promastigotes from different species to determine their specific features and to identify new candidate proteins involved in interactions of Leishmania with the host. The exoproteomes differ from the proteomes by a decrease in the average molecular weight per protein, in disordered amino acid residues and in basic proteins. The exoproteome of the visceral species is significantly enriched in sites predicted to be phosphorylated as well as in features frequently associated with molecular interactions (intrinsic disorder, number of disordered binding regions per protein, interaction and/or trafficking motifs) compared to the other species. The visceral species might thus have a larger interaction repertoire with the host than the other species. Less than 10% of the exoproteomes contain heparin-binding and RGD sequences, and ~30% the host targeting signal RXLXE/D/Q. These latter proteins might thus be exported inside the host cell during the intracellular stage of the infection. Furthermore we have identified nine protein families conserved in the three exoproteomes with specific combinations of Pfam domains and selected eleven proteins containing at least three interaction and/or trafficking motifs including two splicing factors, phosphomannomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, the paraflagellar rod protein-1D and a putative helicase. Their role in host-Leishmania interactions warrants further investigation but the putative ATP-dependent DEAD/H RNA helicase, which contains numerous interaction motifs, a host targeting signal and two disordered regions, is a very promising candidate. PMID:24096101

  19. 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

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

    PubMed

    McPherson, M C; Delany, M E

    2016-02-01

    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

  1. Haemonchus contortus P-Glycoproteins Interact with Host Eosinophil Granules: A Novel Insight into the Role of ABC Transporters in Host-Parasite Interaction

    PubMed Central

    Issouf, Mohamed; Guégnard, Fabrice; Koch, Christine; Le Vern, Yves; Blanchard-Letort, Alexandra; Che, Hua; Beech, Robin N.; Kerboeuf, Dominique; Neveu, Cedric

    2014-01-01

    Eosinophils are one of the major mammalian effector cells encountered by helminths during infection. In the present study, we investigated the effects of eosinophil granule exposure on the sheep parasitic nematode Haemonchus contortus as a model. H. contortus eggs exposed to eosinophil granule products showed increased rhodamine 123 efflux and this effect was not due to loss of egg integrity. Rh123 is known to be a specific P-glycoprotein (Pgp) substrate and led to the hypothesis that in addition to their critical role in xenobiotic resistance, helminth ABC transporters such as Pgp may also be involved in the detoxification of host cytotoxic products. We showed by quantitative RT-PCR that, among nine different H. contortus Pgp genes, Hco-pgp-3, Hco-pgp-9.2, Hco-pgp-11 and, Hco-pgp-16 were specifically up-regulated in parasitic life stages suggesting a potential involvement of these Pgps in the detoxification of eosinophil granule products. Using exsheathed L3 larvae that mimic the first life stage in contact with the host, we demonstrated that eosinophil granules induced a dose dependent overexpression of Hco-pgp-3 and the closely related Hco-pgp-16. Taken together, our results provide the first evidence that a subset of helminth Pgps interact with, and could be involved in the detoxification of, host products. This opens the way for further studies aiming to explore the role of helminth Pgps in the host-parasite interaction, including evasion of the host immune response. PMID:24498376

  2. Parasite co-infection and interaction as drivers of host heterogeneity.

    PubMed

    Cattadori, I M; Boag, B; Hudson, P J

    2008-03-01

    We examined the hypothesis that the interaction between concomitant infecting parasites modifies host susceptibility, parasite intensity and the pattern of parasite distribution within the host population. We used a 26 year time series of three common parasites in a natural population of rabbits: two gastrointestinal nematodes (Trichostrongylus retortaeformis and Graphidium strigosum) and the immunosuppressive myxoma virus. The frequency distribution of nematodes in the host population and the relationship between host age and nematode intensity were explored in rabbits with either single or dual nematode infections and rabbits infected with the nematodes and myxoma virus. The aggregation of T. retortaeformis and G. strigosum among the rabbits varied with the nature of the co-infection both in male and female hosts. The two nematodes exhibited different age-intensity profiles: G. strigosum intensity increased exponentially with host age while T. retortaeformis intensity exhibited a convex shape. The presence of a secondary infection did not change the age-intensity profile for G. strigosum but for T. retortaeformis co-infection (either both nematodes or myxoma-nematodes) resulted in significantly greater intensities in adult hosts. Results suggest that multi-species infections contributed to aggregation of parasites in the host population and to seasonal variation in intensity, but also enhanced differences in parasitism between sexes. This effect was apparent for T. retortaeformis, which appears to elicit a strong acquired immune response but not for G. strigosum which does not produce any evident immune reaction. We concluded that concomitant infections mediated by host immunity are important in modifying host susceptibility and influencing heterogeneity amongst individual hosts. PMID:17936286

  3. New ex vivo reporter assay system reveals that σ factors of an unculturable pathogen control gene regulation involved in the host switching between insects and plants

    PubMed Central

    Ishii, Yoshiko; Kakizawa, Shigeyuki; Oshima, Kenro

    2013-01-01

    Abstract Analysis of the environmental regulation of bacterial gene expression is important for understanding the nature, pathogenicity, and infection route of many pathogens. “Candidatus Phytoplasma asteris”, onion yellows strain M (OY-M), is a phytopathogenic bacterium that is able to adapt to quite different host environments, including plants and insects, with a relatively small ∼850 kb genome. The OY-M genome encodes two sigma (σ) factors, RpoD and FliA, that are homologous to Escherichia coli σ70 and σ28, respectively. Previous studies show that gene expression of OY-M dramatically changes upon the response to insect and plant hosts. However, very little is known about the relationship between the two σ factors and gene regulatory systems in OY-M, because phytoplasma cannot currently be cultured in vitro. Here, we developed an Escherichia coli-based ex vivo reporter assay (EcERA) system to evaluate the transcriptional induction of phytoplasmal genes by the OY-M-derived σ factors. EcERA revealed that highly expressed genes in insect and plant hosts were regulated by RpoD and FliA, respectively. We also demonstrated that rpoD expression was significantly higher in insect than in plant hosts and fliA expression was similar between the hosts. These data indicate that phytoplasma-derived RpoD and FliA play key roles in the transcriptional switching mechanism during host switching between insects and plants. Our study will be invaluable to understand phytoplasmal transmission, virulence expression in plants, and the effect of infection on insect fitness. In addition, the novel EcERA system could be broadly applied to reveal transcriptional regulation mechanisms in other unculturable bacteria. Phytoplasma, an unculturable plant pathogen, could infect plant and insect cells, and dramatically changes their genes upon the response to these hosts. By a new system developed in this study, interactions between phytoplasma promoters and sigma factors were

  4. Host-microbe interactions in the small bowel

    PubMed Central

    Davies, Julie M.; Abreu, Maria T.

    2015-01-01

    Purpose of Review The intestine, home to a vast microbiome, balances its immune reactivity on a knife’s edge. This review will summarize recent studies examining innate immune signals that shape the microbiota, and how pathogens can usurp protective responses to their advantage. Recent findings Innate signaling uses several pathways to maintain epithelial defense. Toll-like receptor signaling through myeloid differentiation factor 88 maintains segregation between bacteria and the epithelium through production of anti-microbial proteins and inflammasome signaling mediates efficient goblet cell release of mucus containing granules. Conversely, negative regulators of TLR signaling help maintain a healthy microbiota resistant to pathogen infection. Methods to evade immune elimination by pathogens associated with human infections and inflammatory bowel disease are described. Emerging evidence that pattern recognition receptors can differentiate between commensals and pathogens will be examined. Summary The balance of innate signaling in the intestine is crucial to homeostasis: too little and bacteria can directly contact the epithelium, too much depletes the protective microbiota creating a niche for pathogens. Understanding the dynamic interaction between the immune system and the microbiota in a variety of infection and inflammation models will hopefully translate to new therapies. PMID:25426971

  5. 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

  6. Interaction between host genotype and environmental conditions affects bacterial density in Wolbachia symbiosis.

    PubMed

    Mouton, Laurence; Henri, Hélène; Charif, Delphine; Boulétreau, Michel; Vavre, Fabrice

    2007-04-22

    Regulation of microbial population density is a necessity in stable symbiotic interactions. In Wolbachia symbiosis, both bacterial and host genotypes are involved in density regulation, but environmental factors may also affect bacterial population density. Here, we studied the interaction between three strains of Wolbachia in two divergent homozygous lines of the wasp Leptopilina heterotoma at two different temperatures. Wolbachia density varied between the two host genotypes at only one temperature. Moreover, at this temperature, reciprocal-cross F1 insects displayed identical Wolbachia densities, which were intermediate between the densities in the two parental lines. While these findings confirm that the host genotype plays an important role in Wolbachia density, they also highlight its interaction with environmental conditions, making possible the evolution of local adaptations for the regulation of Wolbachia density. PMID:17251124

  7. 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

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

    PubMed

    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

  9. Influence of the Virus LbFV and of Wolbachia in a Host-Parasitoid Interaction

    PubMed Central

    Woolfit, Megan; Vavre, Fabrice; O'Neill, Scott L.; Varaldi, Julien

    2012-01-01

    Symbionts are widespread and might have a substantial effect on the outcome of interactions between species, such as in host-parasitoid systems. Here, we studied the effects of symbionts on the outcome of host-parasitoid interactions in a four-partner system, consisting of the parasitoid wasp Leptopilina boulardi, its two hosts Drosophila melanogaster and D. simulans, the wasp virus LbFV, and the endosymbiotic bacterium Wolbachia. The virus is known to manipulate the superparasitism behavior of the parasitoid whereas some Wolbachia strains can reproductively manipulate and/or confer pathogen protection to Drosophila hosts. We used two nuclear backgrounds for both Drosophila species, infected with or cured of their respective Wolbachia strains, and offered them to L. boulardi of one nuclear background, either infected or uninfected by the virus. The main defence mechanism against parasitoids, i.e. encapsulation, and other important traits of the interaction were measured. The results showed that virus-infected parasitoids are less frequently encapsulated than uninfected ones. Further experiments showed that this viral effect involved both a direct protective effect against encapsulation and an indirect effect of superparasitism. Additionally, the Wolbachia strain wAu affected the encapsulation ability of its Drosophila host but the direction of this effect was strongly dependent on the presence/absence of LbFV. Our results confirmed the importance of heritable symbionts in the outcome of antagonistic interactions. PMID:22558118

  10. A dual role for plant quinone reductases in host-fungus interaction.

    PubMed

    Heyno, Eiri; Alkan, Noam; Fluhr, Robert

    2013-11-01

    Quinone reductases (QR, EC 1.5.6.2) are flavoproteins that protect organisms from oxidative stress. The function of plant QRs has not as yet been addressed in vivo despite biochemical evidence for their involvement in redox reactions. Here, using knock-out (KO) and overexpressing lines, we studied the protective role of two groups of Arabidopsis thaliana cytosolic QRs, Nqr (NAD(P)H:quinone oxidoreductase) and Fqr (flavodoxin-like quinone reductase), in response to infection by necrotrophic fungi. The KO lines nqr(-) and fqr1(-) displayed significantly slower development of lesions of Botrytis cinerea and Sclerotinia sclerotium in comparison to the wild type (WT). Consistent with this observation, the overexpressing line FQR1(+) was hypersensitive to the pathogens. Both the nqr(-) and fqr1(-) displayed increased fluorescence of 2',7'-dichlorofluorescein,‬ a reporter for reactive oxygen species in response to B. cinerea. Infection by B. cinerea was accompanied with increased Nqr and Fqr1 protein levels in the WT as revealed by western blotting. In addition, a marked stimulation of salicylic acid-sensitive transcripts and suppression of jasmonate-sensitive transcripts was observed in moderately wounded QR KO mutant leaves, a condition mimicking the early stage of infection. In contrast to the above observations, germination of conidia was accelerated on leaves of QR KO mutants in comparison with the WT and FQR1(+). The same effect was observed in water-soluble leaf surface extracts. It is proposed that the altered interaction between B. cinerea and the QR mutants is a consequence of subtly altered redox state of the host, which perturbs host gene expression in response to environmental stress such as fungal growth.‬‬‬‬‬‬ PMID:23464356

  11. 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. PMID:27121257

  12. Dual RNA-seq of Nontypeable Haemophilus influenzae and Host Cell Transcriptomes Reveals Novel Insights into Host-Pathogen Cross Talk

    PubMed Central

    Baddal, Buket; Muzzi, Alessandro; Censini, Stefano; Calogero, Raffaele A.; Torricelli, Giulia; Guidotti, Silvia; Taddei, Anna R.; Covacci, Antonello; Pizza, Mariagrazia; Rappuoli, Rino; Pezzicoli, Alfredo

    2015-01-01

    ABSTRACT The ability to adhere and adapt to the human respiratory tract mucosa plays a pivotal role in the pathogenic lifestyle of nontypeable Haemophilus influenzae (NTHi). However, the temporal events associated with a successful colonization have not been fully characterized. In this study, by reconstituting the ciliated human bronchial epithelium in vitro, we monitored the global transcriptional changes in NTHi and infected mucosal epithelium simultaneously for up to 72 h by dual RNA sequencing. The initial stage of colonization was characterized by the binding of NTHi to ciliated cells. Temporal profiling of host mRNA signatures revealed significant dysregulation of the target cell cytoskeleton elicited by bacterial infection, with a profound effect on the intermediate filament network and junctional complexes. In response to environmental stimuli of the host epithelium, NTHi downregulated its central metabolism and increased the expression of transporters, indicating a change in the metabolic regime due to the availability of host substrates. Concurrently, the oxidative environment generated by infected cells instigated bacterial expression of stress-induced defense mechanisms, including the transport of exogenous glutathione and activation of the toxin-antitoxin system. The results of this analysis were validated by those of confocal microscopy, Western blotting, Bio-plex, and real-time quantitative reverse transcription-PCR (qRT-PCR). Notably, as part of our screening for novel signatures of infection, we identified a global profile of noncoding transcripts that are candidate small RNAs (sRNAs) regulated during human host infection in Haemophilus species. Our data, by providing a robust and comprehensive representation of the cross talk between the host and invading pathogen, provides important insights into NTHi pathogenesis and the development of efficacious preventive strategies. PMID:26578681

  13. Exploration of Panviral Proteome: High-Throughput Cloning and Functional Implications in Virus-host Interactions

    PubMed Central

    Yu, Xiaobo; Bian, Xiaofang; Throop, Andrea; Song, Lusheng; Moral, Lerys Del; Park, Jin; Seiler, Catherine; Fiacco, Michael; Steel, Jason; Hunter, Preston; Saul, Justin; Wang, Jie; Qiu, Ji; Pipas, James M.; LaBaer, Joshua

    2014-01-01

    Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology. With more than 2,000 viral genomes sequenced, only a small percent of them are well investigated. The access of these viral open reading frames (ORFs) in a flexible cloning format would greatly facilitate both in vitro and in vivo virus-host interaction studies. However, the overall progress of viral ORF cloning has been slow. To facilitate viral studies, we are releasing the initiation of our panviral proteome collection of 2,035 ORF clones from 830 viral genes in the Gateway® recombinational cloning system. Here, we demonstrate several uses of our viral collection including highly efficient production of viral proteins using human cell-free expression system in vitro, global identification of host targets for rubella virus using Nucleic Acid Programmable Protein Arrays (NAPPA) containing 10,000 unique human proteins, and detection of host serological responses using micro-fluidic multiplexed immunoassays. The studies presented here begin to elucidate host-viral protein interactions with our systemic utilization of viral ORFs, high-throughput cloning, and proteomic technologies. These valuable plasmid resources will be available to the research community to enable continued viral functional studies. PMID:24955142

  14. Integrated whole-genome screening for Pseudomonas aeruginosa virulence genes using multiple disease models reveals that pathogenicity is host specific.

    PubMed

    Dubern, Jean-Frédéric; Cigana, Cristina; De Simone, Maura; Lazenby, James; Juhas, Mario; Schwager, Stephan; Bianconi, Irene; Döring, Gerd; Eberl, Leo; Williams, Paul; Bragonzi, Alessandra; Cámara, Miguel

    2015-11-01

    Pseudomonas aeruginosa is a multi-host opportunistic pathogen causing a wide range of diseases because of the armoury of virulence factors it produces, and it is difficult to eradicate because of its intrinsic resistance to antibiotics. Using an integrated whole-genome approach, we searched for P. aeruginosa virulence genes with multi-host relevance. We constructed a random library of 57 360 Tn5 mutants in P. aeruginosa PAO1-L and screened it in vitro for those showing pleiotropic effects in virulence phenotypes (reduced swarming, exo-protease and pyocyanin production). A set of these pleiotropic mutants were assayed for reduced toxicity in Drosophila melanogaster, Caenorhabditis elegans, human cell lines and mice. Surprisingly, the screening revealed that the virulence of the majority of P. aeruginosa mutants varied between disease models, suggesting that virulence is dependent on the disease model used and hence the host environment. Genomic analysis revealed that these virulence-related genes encoded proteins from almost all functional classes, which were conserved among P. aeruginosa strains. Thus, we provide strong evidence that although P. aeruginosa is capable of infecting a wide range of hosts, many of its virulence determinants are host specific. These findings have important implication when searching for novel anti-virulence targets to develop new treatments against P. aeruginosa. PMID:25845292

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

    PubMed Central

    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. PMID:27004014

  16. Intergenic Sequence Comparison of Escherichia coli Isolates Reveals Lifestyle Adaptations but Not Host Specificity▿

    PubMed Central

    White, A. P.; Sibley, K. A.; Sibley, C. D.; Wasmuth, J. D.; Schaefer, R.; Surette, M. G.; Edge, T. A.; Neumann, N. F.

    2011-01-01

    Establishing the risk of human infection is one of the goals of public health. For bacterial pathogens, the virulence and zoonotic potential can often be related to their host source. Escherichia coli bacteria are common contaminants of water associated with human recreation and consumption, and many strains are pathogenic. In this study, we analyzed three promoter-containing intergenic regions from 284 diverse E. coli isolates in an attempt to identify molecular signatures associated with specific host types. Promoter sequences controlling production of curli fimbriae, flagella, and nutrient import yielded a phylogenetic tree with isolates clustered by established phylogenetic grouping (A, B1, B2, and D) but not by host source. Virulence genes were more prevalent in groups B2 and D isolates and in human isolates. Group B1 isolates, primarily from nonhuman sources, were the most genetically similar, indicating that they lacked molecular adaptations to specific host environments and were likely host generalists. Conversely, B2 isolates, primarily from human sources, displayed greater genetic distances and were more likely to be host adapted. In agreement with these hypotheses, prevalence of σS activity and the rdar morphotype, phenotypes associated with environmental survival, were significantly higher in B1 isolates than in B2 isolates. Based on our findings, we speculate that E. coli host specificity is not defined by genome-wide sequence changes but, rather, by the presence or absence of specific genes and associated promoter elements. Furthermore, the requirements for colonization of the human gastrointestinal tract may lead to E. coli lifestyle changes along with selection for increased virulence. PMID:21908635

  17. 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

  18. 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. PMID:26902688

  19. Interactions Between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease

    PubMed Central

    Abraham, Clara; Medzhitov, Ruslan

    2013-01-01

    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. PMID:21530739

  20. 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

  1. Aggregation, stability, and oscillations in different models for host-macroparasite interactions.

    PubMed

    Rosà, Roberto; Pugliese, Andrea

    2002-05-01

    Aggregation is generally recognized as an important factor in the dynamics of host-macroparasite interactions and it has been found relevant in stabilizing the dynamics toward an equilibrium coexistence. In this paper we review the models of Anderson and May (1978, J. Anim. Ecol. 47, 219-247, 249-267) and compare them with some more recently developed models, which incorporate explicit mechanisms (multiple infections or host heterogeneity) for generating aggregation and different degrees of mathematical accuracy. We found that the stabilization yielded by aggregation depends strongly on the mechanism producing the aggregation: multiple infections are much less stabilizing than when aggregation is assumed to be fixed from the outside, while the opposite holds for host heterogeneity. We also give analytical estimates of the period of oscillations occurring when the equilibrium is unstable. Finally, we explore in these models the role of aggregation in host regulation and in determining a threshold value for parasite establishment. PMID:12027618

  2. 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

  3. Multifunctional proteins revealed by overlapping clustering in protein interaction network

    PubMed Central

    Chapple, Charles E.; Guénoche, Alain; Brun, Christine

    2012-01-01

    Motivation: Multifunctional proteins perform several functions. They are expected to interact specifically with distinct sets of partners, simultaneously or not, depending on the function performed. Current graph clustering methods usually allow a protein to belong to only one cluster, therefore impeding a realistic assignment of multifunctional proteins to clusters. Results: Here, we present Overlapping Cluster Generator (OCG), a novel clustering method which decomposes a network into overlapping clusters and which is, therefore, capable of correct assignment of multifunctional proteins. The principle of OCG is to cover the graph with initial overlapping classes that are iteratively fused into a hierarchy according to an extension of Newman's modularity function. By applying OCG to a human protein–protein interaction network, we show that multifunctional proteins are revealed at the intersection of clusters and demonstrate that the method outperforms other existing methods on simulated graphs and PPI networks. Availability: This software can be downloaded from http://tagc.univ-mrs.fr/welcome/spip.php?rubrique197 Contact: brun@tagc.univ-mrs.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22080466

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

    PubMed Central

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

    2013-01-01

    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. PMID:23487774

  5. Supramolecular Porphyrin Copolymer Assembled through Host-Guest Interactions and Metal-Ligand Coordination.

    PubMed

    Kinjo, Kanashi; Hirao, Takehiro; Kihara, Shin-ichi; Katsumoto, Yukiteru; Haino, Takeharu

    2015-12-01

    Bisporphyrin cleft molecule 1 Zn possessing a guest moiety assembled to form supramolecular polymers through host-guest interactions. Bispyridine cross-linkers created interchain connections among the supramolecular polymers to form networked polymers in solution. Solution viscometry confirmed that the cross-linked supramolecular polymers were highly entangled. Frequency-dependent linear viscoelastic spectroscopy revealed that the supramolecular polymers generated well-entangled solutions with associating and networking polymers, whereas the solid-like aggregates moved individually without breaking and reforming structures below the transition temperature of 9.6 °C. Morphological transition of the supramolecular polymers was evidenced by AFM images; the non-cross-linked polymer resulted in wide-spread thin networks, while the cross-linked networks produced thicker worm-like nanostructures. The supramolecular networks gelled in 1,1,2,2-tetrachloroethane, and an elastic free-standing film was fabricated with a Young's modulus of 1 GPa. PMID:26486784

  6. 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

    2014-01-01

    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. PMID:25203297

  7. Single-cell genomics-based analysis of virus-host interactions in marine surface bacterioplankton.

    PubMed

    Labonté, Jessica M; Swan, Brandon K; Poulos, Bonnie; Luo, Haiwei; Koren, Sergey; Hallam, Steven J; Sullivan, Matthew B; Woyke, Tanja; Wommack, K Eric; Stepanauskas, Ramunas

    2015-11-01

    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. 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. Our 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. PMID:25848873

  8. Interactions of minute virus of mice and adenovirus with host nucleoli.

    PubMed Central

    Walton, T H; Moen, P T; Fox, E; Bodnar, J W

    1989-01-01

    Biochemical evidence is presented that both minute virus of mice (MVM) and adenovirus interact with the nucleolus during lytic growth and that MVM can also target specific changes involving nucleolar components in adenovirus-infected cells. These virus-nucleolus interactions were studied by analysis of intranuclear compartmentalization of both viral DNAs and host nucleolar proteins: (i) MVM in mouse cells (its normal host) replicates its DNA in the host nucleoli; (ii) specific nucleolar proteins as well as small nuclear ribonucleoprotein antigens are recompartmentalized to multiple intranuclear foci in adenovirus-infected HeLa cells; and (iii) when adenovirus helps MVM DNA replication in a nonpermissive human cell (HeLa), the MVM DNA is also recompartmentalized for synthesis. The data suggest mechanisms for disruption of nucleolar function common to oncogenic or oncolytic virus lytic growth and cell transformation. Images PMID:2760977

  9. 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

    2014-01-01

    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

  10. Group 3 innate lymphoid cells: regulating host-commensal bacteria interactions in inflammation and cancer.

    PubMed

    Goc, Jeremy; Hepworth, Matthew R; Sonnenberg, Gregory F

    2016-01-01

    A delicate balance exists between the mammalian immune system and normally beneficial commensal bacteria that colonize the gastrointestinal tract, which is necessary to maintain tissue homeostasis. Dysregulation of these interactions between the host and commensal bacteria is causally associated with chronic inflammation and the development of cancer. In contrast, recent reports have highlighted that commensal bacteria also play an essential role in promoting anti-tumor immune responses in several contexts, highlighting a paradox whereby interactions between the host and commensal bacteria can influence both pro- and anti-tumor immunity. Given the critical roles for group 3 innate lymphoid cells (ILC3s) in regulating inflammation, tissue repair and host-microbe interactions in the intestine, here we discuss new evidence that ILC3s may profoundly influence the development, progression and control of tumors. In this review, we provide an overview of recent advances in understanding the impact of commensal bacteria on tumorigenesis, discuss recent findings identifying ILC3s as critical regulators of host-microbe interactions and highlight the emerging role of this immune cell population in cancer and their potential implication as a therapeutic target. PMID:26451009

  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. 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

  13. 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

  14. Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level

    PubMed Central

    Smati, Mounira; Clermont, Olivier; Bleibtreu, Alexandre; Fourreau, Frédéric; David, Anthony; Daubié, Anne-Sophie; Hignard, Cécile; Loison, Odile; Picard, Bertrand; Denamur, Erick

    2015-01-01

    The primary habitat of the Escherichia coli species is the gut of warm-blooded vertebrates. The E. coli species is structured into four main phylogenetic groups A, B1, B2, and D. We estimated the relative proportions of these phylogroups in the feces of 137 wild and domesticated animals with various diets living in the Ile de France (Paris) region by real-time PCR. We distinguished three main clusters characterized by a particular abundance of two or more phylogroups within the E. coli animal commensal populations, which we called “enterocolitypes” by analogy with the enterotypes defined in the human gut microbiota at the genus level. These enterocolitypes were characterized by a dominant (>50%) B2, B1, or A phylogroup and were associated with different host species, diets, and habitats: wild and herbivorous species (wild rabbits and deer), domesticated herbivorous species (domesticated rabbits, horses, sheep, and cows), and omnivorous species (boar, pigs, and chickens), respectively. By analyzing retrospectively the data obtained using the same approach from 98 healthy humans living in Ile de France (Smati et al. 2013, Appl. Environ. Microbiol. 79, 5005–5012), we identified a specific human enterocolitype characterized by the dominant and/or exclusive (>90%) presence of phylogroup B2. We then compared B2 strains isolated from animals and humans, and revealed that human and animal strains differ regarding O-type and B2 subgroup. Moreover, two genes, sfa/foc and clbQ, were associated with the exclusive character of strains, observed only in humans. In conclusion, a complex network of interactions exists at several levels (genus and intra-species) within the intestinal microbiota. PMID:26033772

  15. Probing the limit of weak host-guest interactions: insertion compounds of mercury(II) halides with microporous SiO(2) hosts.

    PubMed

    Wirnsberger, Gernot; Pillep, Bernhard M; Popitsch, Alois; Knoll, Peter; Behrens, Peter

    2002-09-01

    Mercury(II) halides HgX(2) (X=Cl, Br, I) were inserted into the voids of the crystalline microporous SiO(2) modifications deca-dodecasil 3R (short term: DDR), silica-theta-1 (TON), silica-ferrierite (FER) and silicalite-1 (MFI) by vapour phase loading. The properties of the occluded guest species were studied by X-ray absorption spectroscopy (X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis), UV/Vis spectroscopy, and IR and Raman spectroscopy. The methods reveal the presence of HgX(2) molecules in the insertion compounds. The interactions between these electroneutral guest molecules and the electroneutral surrounding SiO(2) framework are weak. In addition, no indication of any significant guest-guest interaction between the embedded molecules was found, in contrast to the analogous iodine insertion compounds, where these become more important with increasing pore dimensionality (G. Wirnsberger et al., Angew. Chem. 1996, 108, 2951-2953; Angew. Chem. Int. Ed. Engl. 1996, 35, 2777). Analysis of the HgL(3) EXAFS confirms a coordination number of two for Hg and gives HgX bond lengths of 2.26 +/- 0.02, 2.38 +/- 0.02 and 2.57 +/- 0.02 A for the trapped HgCl(2), HgBr(2) and HgI(2) molecules, respectively. These values are very close to those of the corresponding molecules in the vapour phase and are the shortest determined for HgX(2) molecules in solid-state compounds to date (a comparably short distance only appears in the recently reported [Cu(2-pyrazinecarboxylato)(2)HgI(2)] x HgI(2) with d(Hg[bond]I)=2.577(2) A; Dong et al., Angew. Chem. 2000, 112, 4441-4443; Angew. Chem. Int. Ed. 2000, 39, 4271). Thus, there emerges a picture of almost unperturbed HgX(2) molecules, similar to those in the vapour phase or in non-coordinating solvents, in a solid crystalline matrix of high temperature stability, a very unusual state of matter. Despite the weakness of the host-guest interactions, investigations on small

  16. Malaria proteomics: insights into the parasite-host interactions in the pathogenic space.

    PubMed

    Bautista, José M; Marín-García, Patricia; Diez, Amalia; Azcárate, Isabel G; Puyet, Antonio

    2014-01-31

    Proteomics is improving malaria research by providing global information on relevant protein sets from the parasite and the host in connection with its cellular structures and specific functions. In the last decade, reports have described biologically significant elements in the proteome of Plasmodium, which are selectively targeted and quantified, allowing for sensitive and high-throughput comparisons. The identification of molecules by which the parasite and the host react during the malaria infection is crucial to the understanding of the underlying pathogenic mechanisms. Hence, proteomics is playing a major role by defining the elements within the pathogenic space between both organisms that change across the parasite life cycle in association with the host transformation and response. Proteomics has identified post-translational modifications in the parasite and the host that are discussed in terms of functional interactions in malaria parasitism. Furthermore, the contribution of proteomics to the investigation of immunogens for potential vaccine candidates is summarized. The malaria-specific technological advances in proteomics are particularly suited now for identifying host-parasite interactions that could lead to promising targets for therapy, diagnosis or prevention. In this review, we examine the knowledge gained on the biology, pathogenesis, immunity and diagnosis of Plasmodium infection from recent proteomic studies. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. PMID:24140976

  17. 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

  18. A microfluidic cell-trapping device for single-cell tracking of host-microbe interactions.

    PubMed

    Delincé, Matthieu J; Bureau, Jean-Baptiste; López-Jiménez, Ana Teresa; Cosson, Pierre; Soldati, Thierry; McKinney, John D

    2016-08-16

    The impact of cellular individuality on host-microbe interactions is increasingly appreciated but studying the temporal dynamics of single-cell behavior in this context remains technically challenging. Here we present a microfluidic platform, InfectChip, to trap motile infected cells for high-resolution time-lapse microscopy. This approach allows the direct visualization of all stages of infection, from bacterial uptake to death of the bacterium or host cell, over extended periods of time. We demonstrate the utility of this approach by co-culturing an established host-cell model, Dictyostelium discoideum, with the extracellular pathogen Klebsiella pneumoniae or the intracellular pathogen Mycobacterium marinum. We show that the outcome of such infections is surprisingly heterogeneous, ranging from abortive infection to death of the bacterium or host cell. InfectChip thus provides a simple method to dissect the time-course of host-microbe interactions at the single-cell level, yielding new insights that could not be gleaned from conventional population-based measurements. PMID:27425421

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

    PubMed

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

    2015-01-01

    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. PMID:26607488

  20. Early Events in Foamy Virus—Host Interaction and Intracellular Trafficking

    PubMed Central

    Berka, Ursula; Hamann, Martin Volker; Lindemann, Dirk

    2013-01-01

    Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication. PMID:23567621

  1. 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

  2. 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

  3. Single-cell genomics-based analysis of virus–host interactions in marine surface bacterioplankton

    PubMed Central

    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

    2015-01-01

    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. 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. Our 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. PMID:25848873

  4. Host parasite communications-Messages from helminths for the immune system: Parasite communication and cell-cell interactions.

    PubMed

    Coakley, Gillian; Buck, Amy H; Maizels, Rick M

    2016-07-01

    Helminths are metazoan organisms many of which have evolved parasitic life styles dependent on sophisticated manipulation of the host environment. Most notably, they down-regulate host immune responses to ensure their own survival, by exporting a range of immuno-modulatory mediators that interact with host cells and tissues. While a number of secreted immunoregulatory parasite proteins have been defined, new work also points to the release of extracellular vesicles, or exosomes, that interact with and manipulate host gene expression. These recent results are discussed in the overall context of how helminths communicate effectively with the host organism. PMID:27297184

  5. 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.

  6. 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.

  7. Cooperation and conflict in host manipulation: interactions among macro-parasites and micro-organisms

    PubMed Central

    Cézilly, Frank; Perrot-Minnot, Marie-Jeanne; Rigaud, Thierry

    2014-01-01

    Several parasite species are known to manipulate the phenotype of their hosts in ways that enhance their own transmission. Co-occurrence of manipulative parasites, belonging to the same species or to more than one species, in a single host has been regularly observed. Little is known, however, on interactions between co-occurring manipulative parasites with same or different transmission routes. Several models addressing this problem have provided predictions on how cooperation and conflict between parasites could emerge from multiple infections. Here, we review the empirical evidence in favor of the existence of synergistic or antagonistic interactions between co-occurring parasites, and highlight the neglected role of micro-organisms. We particularly discuss the actual importance of selective forces shaping the evolution of interactions between manipulative parasites in relation to parasite prevalence in natural populations, efficiency in manipulation, and type of transmission (i.e., horizontal versus vertical), and we emphasize the potential for future research. PMID:24966851

  8. 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

  9. Real-time imaging and genetic dissection of host-microbe interactions in zebrafish.

    PubMed

    Meijer, Annemarie H; van der Vaart, Michiel; Spaink, Herman P

    2014-01-01

    Many aspects of host interactions with microbes can only be studied in the context of a whole organism. The zebrafish as a model organism has shown to be highly successful for studies of infection biology and the interactions of commensal microbiota with their hosts. Zebrafish are transparent during embryo and larval development and these early life stages are optimally suited for high-resolution imaging of host-microbe interactions in a vertebrate organism. This is facilitated by the development of a variety of fluorescent reporter lines that mark different immune cell types or subcellular compartments where pathogens reside. The zebrafish is an excellent vertebrate model for forward genetic screening and efficient tools for gene knock-down and targeted mutagenesis add further to the strength of this model organism. The use of zebrafish larvae for studying microbial infections has recently led to important new insights in host defence mechanisms, which are highlighted in this review focused on bacterial pathogens. Considering the highly conserved nature of the processes involved, including innate immune recognition, immunometabolism and autophagy, it is to be expected that these recent findings in zebrafish will have great translational value for biomedical applications. PMID:24188444

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

    PubMed Central

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

    2005-01-01

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

  11. Techniques for transferring host-pathogen protein interactions knowledge to new tasks.

    PubMed

    Kshirsagar, Meghana; Schleker, Sylvia; Carbonell, Jaime; Klein-Seetharaman, Judith

    2015-01-01

    We consider the problem of building a model to predict protein-protein interactions (PPIs) between the bacterial species Salmonella Typhimurium and the plant host Arabidopsis thaliana which is a host-pathogen pair for which no known PPIs are available. To achieve this, we present approaches, which use homology and statistical learning methods called "transfer learning." In the transfer learning setting, the task of predicting PPIs between Arabidopsis and its pathogen S. Typhimurium is called the "target task." The presented approaches utilize labeled data i.e., known PPIs of other host-pathogen pairs (we call these PPIs the "source tasks"). The homology based approaches use heuristics based on biological intuition to predict PPIs. The transfer learning methods use the similarity of the PPIs from the source tasks to the target task to build a model. For a quantitative evaluation we consider Salmonella-mouse PPI prediction and some other host-pathogen tasks where known PPIs exist. We use metrics such as precision and recall and our results show that our methods perform well on the target task in various transfer settings. We present a brief qualitative analysis of the Arabidopsis-Salmonella predicted interactions. We filter the predictions from all approaches using Gene Ontology term enrichment and only those interactions involving Salmonella effectors. Thereby we observe that Arabidopsis proteins involved e.g., in transcriptional regulation, hormone mediated signaling and defense response may be affected by Salmonella. PMID:25699028

  12. Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts.

    PubMed

    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

  13. 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

  14. 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

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

    PubMed Central

    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

    2014-01-01

    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. PMID:25203297

  16. 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.

  17. Within-Host Evolution of Pseudomonas aeruginosa Reveals Adaptation toward Iron Acquisition from Hemoglobin

    PubMed Central

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

    2014-01-01

    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. PMID:24803516

  18. Chemical inhibition of RNA viruses reveals REDD1 as a host defense factor.

    PubMed

    Mata, Miguel A; Satterly, Neal; Versteeg, Gijs A; Frantz, Doug; Wei, Shuguang; Williams, Noelle; Schmolke, Mirco; Peña-Llopis, Samuel; Brugarolas, James; Forst, Christian V; White, Michael A; García-Sastre, Adolfo; Roth, Michael G; Fontoura, Beatriz M A

    2011-10-01

    A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (VSV). The mechanism of action occurs through activation of REDD1 expression and concomitant inhibition of mammalian target of rapamycin complex 1 (mTORC1) via TSC1-TSC2 complex. The antiviral activity of naphthalimides was abolished in REDD1(-/-) cells. Inhibition of REDD1 expression by viruses resulted in activation of the mTORC1 pathway. REDD1(-/-) cells prematurely upregulated viral proteins via mTORC1 activation and were permissive to virus replication. In contrast, cells conditionally expressing high concentrations of REDD1 downregulated the amount of viral protein. Thus, REDD1 is a new host defense factor, and chemical activation of REDD1 expression represents a potent antiviral intervention strategy. PMID:21909097

  19. 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

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

    PubMed

    Swaroopa Rani, Tirupaati; Podile, Appa Rao

    2014-04-01

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

  1. Chemical Genetics Reveals Bacterial and Host Cell Functions Critical for Type IV Effector Translocation by Legionella pneumophila

    PubMed Central

    Charpentier, Xavier; Gabay, Joëlle E.; Reyes, Moraima; Zhu, Jing W.; Weiss, Arthur; Shuman, Howard A.

    2009-01-01

    Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters a target host cell. We used chemical genetics, a perturbation strategy that utilizes small molecule inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot activity. From a collection of more than 2,500 annotated molecules we identified specific inhibitors of effector translocation. We found that L. pneumophila effector translocation in macrophages requires host cell factors known to be involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin. Moreover, we found that L. pneumophila phagocytosis and effector translocation also specifically require the receptor protein tyrosine phosphate phosphatases CD45 and CD148. We further show that phagocytosis is required to trigger effector delivery unless intimate contact between the bacteria and the host is artificially generated. In addition, real-time analysis of effector translocation suggests that effector export is rate-limited by phagocytosis. We propose a model in which L. pneumophila utilizes phagocytosis to initiate an intimate contact event required for the translocation of pre-synthesized effector molecules. We discuss the need for host cell participation in the initial step of the infection and its implications in the L. pneumophila lifestyle. Chemical genetic screening provides a novel approach to probe the host cell functions and factors involved in host–pathogen interactions. PMID:19578436

  2. Microbes in the gut: a digestable account of host-symbiont interactions.

    PubMed

    Pai, Rekha; Kang, Gagandeep

    2008-11-01

    The human bowel is host to a diverse group of bacteria with over 500 different bacterial species contributing to this diversity. Until recently these bacteria were regarded as residents without any specific functions. The last two decades have seen a radical change in our understanding of the interactions between the gut flora and their eukaryotic hosts and there is a growing appreciation of the spectrum of functions performed by these symbionts. Intestinal bacteria are recognized for their role in nutrient absorption, mucosal barrier function, angiogenesis, morphogenesis and postnatal maturation of intestinal cell lineages, intestinal motility and more importantly maturation of gut associated lymphoid tissue (GALT). Although gut flora are implicated in certain pathological disorders, their remarkable contributions to health and homeostasis of the host need to be recognized and understood. PMID:19179677

  3. Designed self-assembly of molecular necklaces using host-stabilized charge-transfer interactions.

    PubMed

    Ko, Young Ho; Kim, Kyungpil; Kang, Jin-Koo; Chun, Hyungphil; Lee, Jae Wook; Sakamoto, Shigeru; Yamaguchi, Kentaro; Fettinger, James C; Kim, Kimoon

    2004-02-25

    A novel approach to the noncovalent synthesis of molecular necklaces successfully led to the first quantitative self-assembly of a molecular necklace [6]MN, in which five small rings are threaded on a large ring, from 10 components. Our strategy involves the host-guest complex formation between the molecular host cucurbit[8]uril (CB[8]) and a guest molecule in which an electron donor and an electron acceptor unit are connected by a rigid linker with a proper angle, to form a cyclic oligomer through the host-stabilized intermolecular charge-transfer (CT) complex formation. In the structure of the molecular necklace [6]MN, five molecules of the guest form a cyclic framework by the intermolecular CT interactions, on which five CB[8] molecules are threaded with an arrangement reminiscent of a five-fold propeller. The molecular necklace measures approximately 3.7 nm in diameter and approximately 1.8 nm in thickness. PMID:14971915

  4. Utilization of zebrafish for intravital study of eukaryotic pathogen–host interactions

    PubMed Central

    Gratacap, Remi L.; Wheeler, Robert T.

    2014-01-01

    Unique imaging tools and practical advantages have made zebrafish a popular model to investigate in vivo host–pathogen interactions. These studies have uncovered details of the mechanisms involved in several human infections. Until recently, studies using this versatile host were limited to viral and prokaryotic pathogens. Eukaryotic pathogens are a diverse group with a major impact on the human and fish populations. The relationships of eukaryote pathogens with their hosts are complex and many aspects remain obscure. The small and transparent zebrafish, with its conserved immune system and amenability to genetic manipulation, make it an exciting model for quantitative study of the core strategies of eukaryotic pathogens and their hosts. The only thing to do now is realize its potential for advancement of biomedical and aquaculture research. PMID:24491522

  5. 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

  6. 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

  7. Transcriptional responses of invasive and indigenous whiteflies to different host plants reveal their disparate capacity of adaptation.

    PubMed

    Xu, Hong-Xing; Hong, Yue; Zhang, Min-Zhu; Wang, Yong-Liang; Liu, Shu-Sheng; Wang, Xiao-Wei

    2015-01-01

    The whitefly Bemisia tabaci contains more than 35 cryptic species. The higher adaptability of Middle East-Asia Minor 1 (MEAM1) cryptic species has been recognized as one important factor for its invasion and displacement of other indigenous species worldwide. Here we compared the performance of the invasive MEAM1 and the indigenous Asia II 3 whitefly species following host plant transfer from a suitable host (cotton) to an unsuitable host (tobacco) and analyzed their transcriptional responses. After transfer to tobacco for 24 h, MEAM1 performed much better than Asia II 3. Transcriptional analysis showed that the patterns of gene regulation were very different with most of the genes up-regulated in MEAM1 but down-regulated in Asia II 3. Whereas carbohydrate and energy metabolisms were repressed in Asia II 3, the gene expression and protein metabolisms were activated in MEAM1. Compared to the constitutive high expression of detoxification genes in MEAM1, most of the detoxification genes were down-regulated in Asia II 3. Enzymatic activities of P450, GST and esterase further verified that the detoxification of MEAM1 was much higher than that of Asia II 3. These results reveal obvious differences in responses of MEAM1 and Asia II 3 to host transfer. PMID:26041313

  8. Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry.

    PubMed

    Ohmura, Mitsuyo; Hishiki, Takako; Yamamoto, Takehiro; Nakanishi, Tsuyoshi; Kubo, Akiko; Tsuchihashi, Kenji; Tamada, Mayumi; Toue, Sakino; Kabe, Yasuaki; Saya, Hideyuki; Suematsu, Makoto

    2015-04-30

    CD44 expressed in cancer cells was shown to stabilize cystine transporter (xCT) that uptakes cystine and excretes glutamate to supply cysteine as a substrate for reduced glutathione (GSH) for survival. While targeting CD44 serves as a potentially therapeutic stratagem to attack cancer growth and chemoresistance, the impact of CD44 targeting in cancer cells on metabolic systems of tumors and host tissues in vivo remains to be fully determined. This study aimed to reveal effects of CD44 silencing on alterations in energy metabolism and sulfur-containing metabolites in vitro and in vivo using capillary electrophoresis-mass spectrometry and quantitative imaging mass spectrometry (Q-IMS), respectively. In an experimental model of xenograft transplantation of human colon cancer HCT116 cells in superimmunodeficient NOG mice, snap-frozen liver tissues containing metastatic tumors were examined by Q-IMS. As reported previously, short hairpin CD44 RNA interference (shCD44) in cancer cells caused significant regression of tumor growth in the host liver. Under these circumstances, the CD44 knockdown suppressed polyamines, GSH and energy charges not only in metastatic tumors but also in the host liver. In culture, HCT116 cells treated with shCD44 decreased total amounts of methionine-pool metabolites including spermidine and spermine, and reactive cysteine persulfides, suggesting roles of these metabolites for cancer growth. Collectively, these results suggest that CD44 expressed in cancer accounts for a key regulator of metabolic interplay between tumor and the host tissue. PMID:25461272

  9. Human cytomegalovirus RL13 protein interacts with host NUDT14 protein affecting viral DNA replication.

    PubMed

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

    2016-03-01

    The interaction between the host and human cytomegalovirus (HCMV) is important in determining the outcome of a viral infection. The HCMV RL13 gene product exerts independent, inhibitory effects on viral growth in fibroblasts and epithelial cells. At present, there are few reports on the interactions between the HCMV RL13 protein and human host proteins. The present study provided direct evidence for the specific interaction between HCMV RL13 and host nucleoside diphosphate linked moiety X (nudix)‑type motif 14 (NUDT14), a UDP‑glucose pyrophosphatase, using two‑hybrid screening, an in vitro glutathione S‑transferase pull‑down assay, and co‑immunoprecipitation in human embryonic kidney HEK293 cells. Additionally, the RL13 protein was shown to co‑localize with the NUDT14 protein in the HEK293 cell membrane and cytoplasm, demonstrated using fluorescence confocal microscopy. Decreasing the expression level of NUDT14 via NUDT14‑specific small interfering RNAs increased the number of viral DNA copies in the HCMV‑infected cells. However, the overexpression of NUDT14 in a stably expressing cell line did not affect viral DNA levels significantly in the HCMV infected cells. Based on the known functions of NUDT14, the results of the present study suggested that the interaction between the RL13 protein and NUDT14 protein may be involved in HCMV DNA replication, and that NUDT14 may offer potential in the modulation of viral infection. PMID:26781650

  10. 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. PMID:23757232

  11. Evolutionary diversification through hybridization in a wild host-pathogen interaction.

    PubMed

    Barrett, Luke G; Thrall, Peter H; Burdon, Jeremy J

    2007-07-01

    Coevolutionary outcomes between interacting species are predicted to vary across landscapes, as environmental conditions, gene flow, and the strength of selection vary among populations. Using a combination of molecular, experimental, and field approaches, we describe how broad-scale patterns of environmental heterogeneity, genetic divergence, and regional adaptation have the potential to influence coevolutionary processes in the Linum marginale-Melampsora lini plant-pathogen interaction. We show that two genetically and geographically divergent pathogen lineages dominate interactions with the host across Australia, and demonstrate a hybrid origin for one of the lineages. We further demonstrate that the geographic divergence of the two lineages of M. lini in Australia is related to variation among lineages in virulence, life-history characteristics, and response to environmental conditions. When correlated with data describing regional patterns of variation in host resistance diversity and mating system these observations highlight the potential for gene flow and geographic selection mosaics to generate and maintain coevolutionary diversification in long-standing host-pathogen interactions. PMID:17598744

  12. 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

  13. 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.

  14. Comparative Metagenomics Reveals Host Specific Metavirulomes and Horizontal Gene Transfer Elements in the Chicken Cecum Microbiome

    PubMed Central

    Qu, Ani; Brulc, Jennifer M.; Wilson, Melissa K.; Law, Bibiana F.; Theoret, James R.; Joens, Lynn A.; Konkel, Michael E.; Angly, Florent; Dinsdale, Elizabeth A.; Edwards, Robert A.; Nelson, Karen E.; White, Bryan A.

    2008-01-01

    Background The complex microbiome of the ceca of chickens plays an important role in nutrient utilization, growth and well-being of these animals. Since we have a very limited understanding of the capabilities of most species present in the cecum, we investigated the role of the microbiome by comparative analyses of both the microbial community structure and functional gene content using random sample pyrosequencing. The overall goal of this study was to characterize the chicken cecal microbiome using a pathogen-free chicken and one that had been challenged with Campylobacter jejuni. Methodology/Principal Findings Comparative metagenomic pyrosequencing was used to generate 55,364,266 bases of random sampled pyrosequence data from two chicken cecal samples. SSU rDNA gene tags and environmental gene tags (EGTs) were identified using SEED subsystems-based annotations. The distribution of phylotypes and EGTs detected within each cecal sample were primarily from the Firmicutes, Bacteroidetes and Proteobacteria, consistent with previous SSU rDNA libraries of the chicken cecum. Carbohydrate metabolism and virulence genes are major components of the EGT content of both of these microbiomes. A comparison of the twelve major pathways in the SEED Virulence Subsystem (metavirulome) represented in the chicken cecum, mouse cecum and human fecal microbiomes showed that the metavirulomes differed between these microbiomes and the metavirulomes clustered by host environment. The chicken cecum microbiomes had the broadest range of EGTs within the SEED Conjugative Transposon Subsystem, however the mouse cecum microbiomes showed a greater abundance of EGTs in this subsystem. Gene assemblies (32 contigs) from one microbiome sample were predominately from the Bacteroidetes, and seven of these showed sequence similarity to transposases, whereas the remaining sequences were most similar to those from catabolic gene families. Conclusion/Significance This analysis has demonstrated that

  15. 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

  16. Nonhost diversity and density reduce the strength of parasitoid-host interactions.

    PubMed

    Kehoe, Rachel; Frago, Enric; Barten, Catherin; Jecker, Flurin; van Veen, Frank; Sanders, Dirk

    2016-06-01

    The presence of nonprey or nonhosts is known to reduce the strength of consumer- resource interactions by increasing the consumer's effort needed to find its resource. These interference effects can have a stabilizing effect on consumer-resource dynamics, but have also been invoked to explain parasitoid extinctions. To understand how nonhosts affect parasitoids, we manipulated the density and diversity of nonhost aphids using experimental host-parasitoid communities and tested how this affects parasitation efficiency of two aphid parasitoid species. To further study the behavioral response of parasitoids to nonhosts, we tested for changes in parasitoid time allocation in relation to their host-finding strategies. The proportion of successful attacks (attack rate) in both parasitoid species was reduced by the presence of nonhosts. The parasitoid Aphidius megourae was strongly affected by increasing nonhost diversity with the attack rate dropping from 0.39 without nonhosts to 0.05 with high diversity of nonhosts, while Lysiphlebus fabarum responded less strongly, but in a more pronounced way to an increase in nonhost density. Our experiments further showed that increasing nonhost diversity caused host searching and attacking activity levels to fall in A. megourae, but not in L. fabarum, and that A. megourae changed its behavior after a period of time in the presence of nonhosts by increasing its time spent resting. This study shows that nonhost density and diversity in the environment are crucial determinants for the strength of consumer-resource interactions. Their impact upon a consumer's efficiency strongly depends on its host/prey finding strategy as demonstrated by the different responses for the two parasitoid species. We discuss that these trait-mediated indirect interactions between host and nonhost species are important for community stability, acting either stabilizing or destabilizing depending on the level of nonhost density or diversity present. PMID

  17. 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

    2015-10-01

    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. PMID:26401973

  18. Automated Image Analysis of the Host-Pathogen Interaction between Phagocytes and Aspergillus fumigatus

    PubMed Central

    Guthke, Reinhard; Brakhage, Axel A.; Figge, Marc Thilo

    2011-01-01

    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. PMID

  19. Host-virus interactions in hepatitis B and hepatitis C infection.

    PubMed

    Yoshio, Sachiyo; Kanto, Tatsuya

    2016-05-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-λ3), remains to be elucidated. Human BDCA3(+)DCs have also been shown to be a potent producer of IFN-λ3 in HCV infection, suggesting the possibility that BDCA3(+)DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection. PMID:26894594

  20. The Pathogen-Host Interactions database (PHI-base): additions and future developments

    PubMed Central

    Urban, Martin; Pant, Rashmi; Raghunath, Arathi; Irvine, Alistair G.; Pedro, Helder; Hammond-Kosack, Kim E.

    2015-01-01

    Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). PMID:25414340

  1. 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. PMID:26410623

  2. The Pathogen-Host Interactions database (PHI-base): additions and future developments.

    PubMed

    Urban, Martin; Pant, Rashmi; Raghunath, Arathi; Irvine, Alistair G; Pedro, Helder; Hammond-Kosack, Kim E

    2015-01-01

    Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). PMID:25414340

  3. Molecular characterization reveals distinct genospecies of Anaplasma phagocytophilum from diverse North American hosts

    PubMed Central

    Bradburd, Gideon; Foley, Janet

    2012-01-01

    Anaplasma phagocytophilum is an emerging tick-borne pathogen that infects humans, domestic animals and wildlife throughout the Holarctic. In the far-western United States, multiple rodent species have been implicated as natural reservoirs for A. phagocytophilum. However, the presence of multiple A. phagocytophilum strains has made it difficult to determine which reservoir hosts pose the greatest risk to humans and domestic animals. Here we characterized three genetic markers (23S–5S rRNA intergenic spacer, ank and groESL) from 73 real-time TaqMan PCR-positive A. phagocytophilum strains infecting multiple rodent and reptile species, as well as a dog and a horse, from California. Bayesian and maximum-likelihood phylogenetic analyses of all three genetic markers consistently identified two major clades, one of which consisted of A. phagocytophilum strains infecting woodrats and the other consisting of strains infecting sciurids (chipmunks and squirrels) as well as the dog and horse strains. In addition, analysis of the 23S–5S rRNA spacer region identified two unique and highly dissimilar clades of A. phagocytophilum strains infecting several lizard species. Our findings indicate that multiple unique strains of A. phagocytophilum with distinct host tropisms exist in California. Future epidemiological studies evaluating human and domestic animal risk should incorporate these distinctions. PMID:21921109

  4. Metagenomic Analysis of Streptomyces lividans Reveals Host-Dependent Functional Expression

    PubMed Central

    McMahon, Matthew D.; Guan, Changhui; Handelsman, Jo

    2012-01-01

    Most functional metagenomic studies have been limited by the poor expression of many genes derived from metagenomic DNA in Escherichia coli, which has been the predominant surrogate host to date. To expand the range of expressed genes, we developed tools for construction and functional screening of metagenomic libraries in Streptomyces lividans. We expanded on previously published protocols by constructing a system that enables retrieval and characterization of the metagenomic DNA from biologically active clones. To test the functionality of these methods, we constructed and screened two metagenomic libraries in S. lividans. One was constructed with pooled DNA from 14 bacterial isolates cultured from Alaskan soil and the second with DNA directly extracted from the same soil. Functional screening of these libraries identified numerous clones with hemolytic activity, one clone that produces melanin by a previously unknown mechanism, and one that induces the overproduction of a secondary metabolite native to S. lividans. All bioactive clones were functional in S. lividans but not in E. coli, demonstrating the advantages of screening metagenomic libraries in more than one host. PMID:22427497

  5. 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

  6. Whole genome sequencing revealed host adaptation-focused genomic plasticity of pathogenic Leptospira

    PubMed Central

    Xu, Yinghua; Zhu, Yongzhang; Wang, Yuezhu; Chang, Yung-Fu; Zhang, Ying; Jiang, Xiugao; Zhuang, Xuran; Zhu, Yongqiang; Zhang, Jinlong; Zeng, Lingbing; Yang, Minjun; Li, Shijun; Wang, Shengyue; Ye, Qiang; Xin, Xiaofang; Zhao, Guoping; Zheng, Huajun; Guo, Xiaokui; Wang, Junzhi

    2016-01-01

    Leptospirosis, caused by pathogenic Leptospira spp., has recently been recognized as an emerging infectious disease worldwide. Despite its severity and global importance, knowledge about the molecular pathogenesis and virulence evolution of Leptospira spp. remains limited. Here we sequenced and analyzed 102 isolates representing global sources. A high genomic variability were observed among different Leptospira species, which was attributed to massive gene gain and loss events allowing for adaptation to specific niche conditions and changing host environments. Horizontal gene transfer and gene duplication allowed the stepwise acquisition of virulence factors in pathogenic Leptospira evolved from a recent common ancestor. More importantly, the abundant expansion of specific virulence-related protein families, such as metalloproteases-associated paralogs, were exclusively identified in pathogenic species, reflecting the importance of these protein families in the pathogenesis of leptospirosis. Our observations also indicated that positive selection played a crucial role on this bacteria adaptation to hosts. These novel findings may lead to greater understanding of the global diversity and virulence evolution of Leptospira spp. PMID:26833181

  7. Whole genome sequencing revealed host adaptation-focused genomic plasticity of pathogenic Leptospira.

    PubMed

    Xu, Yinghua; Zhu, Yongzhang; Wang, Yuezhu; Chang, Yung-Fu; Zhang, Ying; Jiang, Xiugao; Zhuang, Xuran; Zhu, Yongqiang; Zhang, Jinlong; Zeng, Lingbing; Yang, Minjun; Li, Shijun; Wang, Shengyue; Ye, Qiang; Xin, Xiaofang; Zhao, Guoping; Zheng, Huajun; Guo, Xiaokui; Wang, Junzhi

    2016-01-01

    Leptospirosis, caused by pathogenic Leptospira spp., has recently been recognized as an emerging infectious disease worldwide. Despite its severity and global importance, knowledge about the molecular pathogenesis and virulence evolution of Leptospira spp. remains limited. Here we sequenced and analyzed 102 isolates representing global sources. A high genomic variability were observed among different Leptospira species, which was attributed to massive gene gain and loss events allowing for adaptation to specific niche conditions and changing host environments. Horizontal gene transfer and gene duplication allowed the stepwise acquisition of virulence factors in pathogenic Leptospira evolved from a recent common ancestor. More importantly, the abundant expansion of specific virulence-related protein families, such as metalloproteases-associated paralogs, were exclusively identified in pathogenic species, reflecting the importance of these protein families in the pathogenesis of leptospirosis. Our observations also indicated that positive selection played a crucial role on this bacteria adaptation to hosts. These novel findings may lead to greater understanding of the global diversity and virulence evolution of Leptospira spp. PMID:26833181

  8. Hepatitis E virus ORF1 encoded non structural protein-host protein interaction network.

    PubMed

    Ojha, Nishant Kumar; Lole, Kavita S

    2016-02-01

    Hepatitis E virus ORF1 encoded non-structural polyprotein (nsP) consist of multiple domains, namely: Methyltransferase, Y-domain, Protease, X-domain, Helicase and RNA dependent RNA polymerase. We have attempted to identify human liver cell proteins that are interacting with HEV ORF1 encoded functional domains by using Y2H screening. A total of 155 protein-protein interactions between HEV-ORF1 and human proteins were identified. Comparative analysis of the HEV-ORF1-Human interaction network with reconstructed human interactome showed that the cellular proteins interacting with HEV-ORF1 are central and interconnected. Enrichment analysis of Gene Ontology and cellular pathways showed that the viral proteins preferentially interacted with the proteins of metabolism and energy generation along with host immune response and ubiquitin proteasomal pathways. The mTOR and focal adhesion pathways were also targeted by the virus. These interactions suggest that HEV probably utilizes important proteins in carbohydrate metabolism, energy generation and iron homoeostasis in the host cells during its establishment. PMID:26689634

  9. 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

  10. 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. PMID:26401317

  11. 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

  12. Induction of Salmonella pathogenicity island 1 under different growth conditions can affect Salmonella–host cell interactions in vitro

    PubMed Central

    Ibarra, J. Antonio; Knodler, Leigh A.; Sturdevant, Daniel E.; Virtaneva, Kimmo; Carmody, Aaron B.; Fischer, Elizabeth R.; Porcella, Stephen F.; Steele-Mortimer, Olivia

    2010-01-01

    Salmonella invade non-phagocytic cells by inducing massive actin rearrangements, resulting in membrane ruffle formation and phagocytosis of the bacteria. This process is mediated by a cohort of effector proteins translocated into the host cell by type III secretion system 1, which is encoded by genes in the Salmonella pathogenicity island (SPI) 1 regulon. This network is precisely regulated and must be induced outside of host cells. In vitro invasive Salmonella are prepared by growth in synthetic media although the details vary. Here, we show that culture conditions affect the frequency, and therefore invasion efficiency, of SPI1-induced bacteria and also can affect the ability of Salmonella to adapt to its intracellular niche following invasion. Aerobically grown late-exponential-phase bacteria were more invasive and this was associated with a greater frequency of SPI1-induced, motile bacteria, as revealed by single-cell analysis of gene expression. Culture conditions also affected the ability of Salmonella to adapt to the intracellular environment, since they caused marked differences in intracellular replication. These findings show that induction of SPI1 under different pre-invasion growth conditions can affect the ability of Salmonella to interact with eukaryotic host cells. PMID:20035008

  13. 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

  14. Systems Biology Analysis of Brucella Infected Peyer's Patch Reveals Rapid Invasion with Modest Transient Perturbations of the Host Transcriptome

    PubMed Central

    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

  15. Comparative genomics of parasitic silkworm microsporidia reveal an association between genome expansion and host adaptation

    PubMed Central

    2013-01-01

    Background Microsporidian Nosema bombycis has received much attention because the pébrine disease of domesticated silkworms results in great economic losses in the silkworm industry. So far, no effective treatment could be found for pébrine. Compared to other known Nosema parasites, N. bombycis can unusually parasitize a broad range of hosts. To gain some insights into the underlying genetic mechanism of pathological ability and host range expansion in this parasite, a comparative genomic approach is conducted. The genome of two Nosema parasites, N. bombycis and N. antheraeae (an obligatory parasite to undomesticated silkworms Antheraea pernyi), were sequenced and compared with their distantly related species, N. ceranae (an obligatory parasite to honey bees). Results Our comparative genomics analysis show that the N. bombycis genome has greatly expanded due to the following three molecular mechanisms: 1) the proliferation of host-derived transposable elements, 2) the acquisition of many horizontally transferred genes from bacteria, and 3) the production of abundnant gene duplications. To our knowledge, duplicated genes derived not only from small-scale events (e.g., tandem duplications) but also from large-scale events (e.g., segmental duplications) have never been seen so abundant in any reported microsporidia genomes. Our relative dating analysis further indicated that these duplication events have arisen recently over very short evolutionary time. Furthermore, several duplicated genes involving in the cytotoxic metabolic pathway were found to undergo positive selection, suggestive of the role of duplicated genes on the adaptive evolution of pathogenic ability. Conclusions Genome expansion is rarely considered as the evolutionary outcome acting on those highly reduced and compact parasitic microsporidian genomes. This study, for the first time, demonstrates that the parasitic genomes can expand, instead of shrink, through several common molecular mechanisms

  16. Porphyrinic supramolecular daisy chains incorporating pillar[5]arene-viologen host-guest interactions.

    PubMed

    Fathalla, Maher; Strutt, Nathan L; Sampath, Srinivasan; Katsiev, Khabiboulakh; Hartlieb, Karel J; Bakr, Osman M; Stoddart, J Fraser

    2015-07-01

    A porphyrin functionalised with pillar[5]arene and a viologen at its 5- and 15-meso positions assembles in a head-to-tail manner, producing linear supramolecular daisy chains in dichloromethane. At high concentrations, it forms an organogel which has been investigated by electron microscopy and rheological measurements, paving the way for the preparation of other functional supramolecular assemblies which harness viologen⊂pillararene host-guest interactions. PMID:26027650

  17. Self-healing supramolecular gels formed by crown ether based host-guest interactions.

    PubMed

    Zhang, Mingming; Xu, Donghua; Yan, Xuzhou; Chen, Jianzhuang; Dong, Shengyi; Zheng, Bo; Huang, Feihe

    2012-07-01

    Automatic repair: a polymer with pendent dibenzo[24]crown-8 units (purple in picture) was cross-linked by two bisammonium salts (green) to form two supramolecular gels based on host-guest interactions. These two gels are stimuli-responsive materials that respond to changes of the pH value and are also self-healing materials, as can be seen by eye and as evidenced by rheological data. PMID:22653895

  18. 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

  19. 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

  20. 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

  1. Dual RNA-Sequencing of Eucalyptus nitens during Phytophthora cinnamomi Challenge Reveals Pathogen and Host Factors Influencing Compatibility.

    PubMed

    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

  2. Nancy E. Beckage (1950-2012): pioneer in insect host-parasite interactions.

    PubMed

    Riddiford, Lynn M; Webb, Bruce A

    2014-01-01

    Nancy E. Beckage is widely recognized for her pioneering work in the field of insect host-parasitoid interactions beginning with endocrine influences of the tobacco hornworm, Manduca sexta, host and its parasitoid wasp Apanteles congregatus (now Cotesia congregata) on each other's development. Moreover, her studies show that the polydnavirus carried by the parasitoid wasp not only protects the parasitoid from the host's immune defenses, but also is responsible for some of the developmental effects of parasitism. Nancy was a highly regarded mentor of both undergraduate and graduate students and more widely of women students and colleagues in entomology. Her service both to her particular area and to entomology in general through participation on federal grant review panels and in the governance of the Entomological Society of America, organization of symposia at both national and international meetings, and editorship of several different journal issues and of several books is legendary. She has left behind a lasting legacy of increased understanding of multilevel endocrine and physiological interactions among insects and other organisms and a strong network of interacting scientists and colleagues in her area of entomology. PMID:24112111

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

    PubMed Central

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

    2014-01-01

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

  4. From Enigma to Tool: Gamma-Ray Burst Reveals Secrets of Host Galaxy

    NASA Astrophysics Data System (ADS)

    2001-05-01

    Five years ago, astronomers knew almost nothing about Gamma Ray Bursts. Now, a team of observers using the National Science Foundation's Very Large Array (VLA) radio telescope has used a gamma-ray burst as a powerful tool to unveil the nature of the galaxy in which it occurred, more than 7 billion light-years away. VLA Images of GRB980703 Host Galaxy "We believe that gamma-ray bursts may become one of the best available tools for studying the history of star formation in the universe," said Edo Berger, a graduate student at Caltech. Berger worked with Caltech astronomy professor Shri Kulkarni and Dale Frail, an astronomer at the National Radio Astronomy Observatory (NRAO) in Socorro, New Mexico, to study a gamma-ray burst first seen on July 3, 1998. The astronomers presented their results at the American Astronomical Society's meeting in Pasadena, CA. "For the first time, we've seen the host galaxy of a gamma-ray burst with a radio telescope," Berger said. "Previously, gamma-ray-burst host galaxies have been seen with optical telescopes, but detecting this galaxy with a radio telescope has given us new clues about the nature of the galaxy itself -- clues we couldn't have gotten any other way," he added. For example, based on optical-telescope studies, astronomers estimated that new stars are forming in the host galaxy at the rate of about the mass equivalent of 20 suns per year. However, data from the radio observations show that the actual star-formation rate is 25 times greater -- the mass equivalent of 500 suns per year. "With the VLA, we are seeing the entire region of star formation in this galaxy, including the areas so dusty that visible light can't get out," said Frail. Gamma-ray bursts are the most powerful explosions since the Big Bang. First discovered in 1967 by a satellite launched to monitor compliance with the atmospheric nuclear test ban treaty, gamma-ray bursts remained one of astronomy's premier mysteries for 30 years. For three decades

  5. 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

  6. The mycobiota: interactions between commensal fungi and the host immune system.

    PubMed

    Underhill, David M; Iliev, Iliyan D

    2014-06-01

    The body is host to a wide variety of microbial communities from which the immune system protects us and that are important for the normal development of the immune system and for the maintenance of healthy tissues and physiological processes. Investigators have mostly focused on the bacterial members of these communities, but fungi are increasingly being recognized to have a role in defining these communities and to interact with immune cells. In this Review, we discuss what is currently known about the makeup of fungal communities in the body and the features of the immune system that are particularly important for interacting with fungi at these sites. PMID:24854590

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Computational approaches for prediction of pathogen-host protein-protein interactions

    PubMed Central

    Nourani, Esmaeil; Khunjush, Farshad; Durmuş, Saliha

    2015-01-01

    Infectious diseases are still among the major and prevalent health problems, mostly because of the drug resistance of novel variants of pathogens. Molecular interactions between pathogens and their hosts are the key parts of the infection mechanisms. Novel antimicrobial therapeutics to fight drug resistance is only possible in case of a thorough understanding of pathogen-host interaction (PHI) systems. Existing databases, which contain experimentally verified PHI data, suffer from scarcity of reported interactions due to the technically challenging and time consuming process of experiments. These have motivated many researchers to address the problem by proposing computational approaches for analysis and prediction of PHIs. The computational methods primarily utilize sequence information, protein structure and known interactions. Classic machine learning techniques are used when there are sufficient known interactions to be used as training data. On the opposite case, transfer and multitask learning methods are preferred. Here, we present an overview of these computational approaches for predicting PHI systems, discussing their weakness and abilities, with future directions. PMID:25759684

  9. 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.

  10. Computational approaches for prediction of pathogen-host protein-protein interactions.

    PubMed

    Nourani, Esmaeil; Khunjush, Farshad; Durmuş, Saliha

    2015-01-01

    Infectious diseases are still among the major and prevalent health problems, mostly because of the drug resistance of novel variants of pathogens. Molecular interactions between pathogens and their hosts are the key parts of the infection mechanisms. Novel antimicrobial therapeutics to fight drug resistance is only possible in case of a thorough understanding of pathogen-host interaction (PHI) systems. Existing databases, which contain experimentally verified PHI data, suffer from scarcity of reported interactions due to the technically challenging and time consuming process of experiments. These have motivated many researchers to address the problem by proposing computational approaches for analysis and prediction of PHIs. The computational methods primarily utilize sequence information, protein structure and known interactions. Classic machine learning techniques are used when there are sufficient known interactions to be used as training data. On the opposite case, transfer and multitask learning methods are preferred. Here, we present an overview of these computational approaches for predicting PHI systems, discussing their weakness and abilities, with future directions. PMID:25759684

  11. 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

  12. Genomic Interaction Profiles in Breast Cancer Reveal Altered Chromatin Architecture

    PubMed Central

    Zeitz, Michael J.; Ay, Ferhat; Heidmann, Julia D.; Lerner, Paula L.

    2013-01-01

    Gene transcription can be regulated by remote enhancer regions through chromosome looping either in cis or in trans. Cancer cells are characterized by wholesale changes in long-range gene interactions, but the role that these long-range interactions play in cancer progression and metastasis is not well understood. In this study, we used IGFBP3, a gene involved in breast cancer pathogenesis, as bait in a 4C-seq experiment comparing normal breast cells (HMEC) with two breast cancer cell lines (MCF7, an ER positive cell line, and MDA-MB-231, a triple negative cell line). The IGFBP3 long-range interaction profile was substantially altered in breast cancer. Many interactions seen in normal breast cells are lost and novel interactions appear in cancer lines. We found that in HMEC, the breast carcinoma amplified sequence gene family (BCAS) 1–4 were among the top 10 most significantly enriched regions of interaction with IGFBP3. 3D-FISH analysis indicated that the translocation-prone BCAS genes, which are located on chromosomes 1, 17, and 20, are in close physical proximity with IGFBP3 and each other in normal breast cells. We also found that epidermal growth factor receptor (EGFR), a gene implicated in tumorigenesis, interacts significantly with IGFBP3 and that this interaction may play a role in their regulation. Breakpoint analysis suggests that when an IGFBP3 interacting region undergoes a translocation an additional interaction detectable by 4C is gained. Overall, our data from multiple lines of evidence suggest an important role for long-range chromosomal interactions in the pathogenesis of cancer. PMID:24019942

  13. Does vegetation complexity affect host plant chemistry, and thus multitrophic interactions, in a human-altered landscape?

    PubMed

    Wäschke, Nicole; Hancock, Christine; Hilker, Monika; Obermaier, Elisabeth; Meiners, Torsten

    2015-09-01

    Anthropogenic land use may shape vegetation composition and affect trophic interactions by altering concentrations of host plant metabolites. Here, we investigated the hypotheses that: (1) plant N and defensive secondary metabolite contents of the herb Plantago lanceolata are affected by land use intensity (LUI) and the surrounding vegetation composition (=plant species richness and P. lanceolata density), and that (2) changes in plant chemistry affect abundances of the herbivorous weevils Mecinus pascuorum and Mecinus labilis, as well as their larval parasitoid Mesopolobus incultus, in the field. We determined plant species richness, P. lanceolata density, and abundances of the herbivores and the parasitoid in 77 grassland plots differing in LUI index in three regions across Germany. We also measured the N and secondary metabolite [the iridoid glycosides (IGs) aucubin and catalpol] contents of P. lanceolata leaves. Mixed-model analysis revealed that: (1) concentrations of leaf IGs were positively correlated with plant species richness; leaf N content was positively correlated with the LUI index. Furthermore: (2) herbivore abundance was not related to IG concentrations, but correlated negatively with leaf N content. Parasitoid abundance correlated positively only with host abundance over the three regions. Structural equation models revealed a positive impact of IG concentrations on parasitoid abundance in one region. We conclude that changes in plant chemistry due to land use and/or vegetation composition may affect higher trophic levels and that the manifestation of these effects may depend on local biotic or abiotic features of the landscape. PMID:25986560

  14. Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions.

    PubMed

    Westermann, Alexander J; Förstner, Konrad U; Amman, Fabian; Barquist, Lars; Chao, Yanjie; Schulte, Leon N; Müller, Lydia; Reinhardt, Richard; Stadler, Peter F; Vogel, Jörg

    2016-01-28

    Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes. PMID:26789254

  15. Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease

    PubMed Central

    Li, Wei; Liu, Liangyi; Gomez, Aurelie; Zhang, Jilu; Ramadan, Abdulraouf; Zhang, Qing; Choi, Sung W.; Zhang, Peng; Greenson, Joel K.; Liu, Chen; Jiang, Di; Virts, Elizabeth; Kelich, Stephanie L.; Chu, Hong Wei; Flynn, Ryan; Blazar, Bruce R.; Hanenberg, Helmut; Hanash, Samir; Paczesny, Sophie

    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

  16. 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

  17. Visualizing infection spread: dual-color fluorescent reporting of virus-host interactions

    PubMed Central

    Swick, Adam; Baltes, Ashley; Yin, John

    2014-01-01

    Although the molecular mechanisms by which host cells defend themselves against viral infection have been studied in great depth, and countermeasures viruses employ to suppress such defensive responses have been widely documented, relatively little attention has been devoted toward elucidating how such interactions between virus and host are resolved over multiple rounds of infection. Here we describe the design, synthesis, and validation of a dual-color fluorescent reporter system to study how viral infections spread through a host cell monolayer and how the cellular innate immune system mounts an antiviral response. We employed recombinant, red fluorescent protein (RFP) expressing mutants of a prototypical RNA virus, vesicular stomatitis virus (VSV) to enable identification and tracking of infected cells. Further, we generated stable reporter cells that use green fluorescent protein (GFP) to report on the expression of IFIT2, an interferon stimulated gene (ISG) involved in the interference of viral protein translation, and a marker of antiviral defense activation. The presence of the fluorescent protein reporters had minimal effects on the normal behavior of the cells or viruses. Moreover, expression of the virus and cell reporters correlated with the kinetics of viral replication and activation of an anti-viral response, respectively. This two-color system enabled us to track and quantify in live cells how viral replication and activation of host defensive responses play out over multiple rounds of infection. Initial study of propagating infections demonstrated that antiviral activation over multiple rounds was critical for slowing and ultimately halting the spread of infection. PMID:24338628

  18. 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

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

    PubMed

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

    2016-01-01

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

  20. "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

  1. Histophagous ciliate Pseudocollinia brintoni and bacterial assemblage interaction with krill Nyctiphanes simplex. II. Host responses.

    PubMed

    Gómez-Gutiérrez, Jaime; Angel-Rodríguez, Jorge A; Tremblay, Nelly; Zenteno-Savín, Tania; Aguilar-Méndez, Mario J; López-Cortés, Alejandro; Robinson, Carlos J

    2015-10-27

    Unlike decapod crustaceans of commercial interest, the krill defense system and its response to parasites and pathogens is virtually unknown. Histophagous ciliates of the genus Pseudocollinia interact with at least 7 krill species in the northeastern Pacific. Although they can cause epizootic events, the physiology of the histophagous ciliate-host interaction and krill (host) defenses remain unknown. From 1 oceanographic survey along the southwestern coast of the Baja California Peninsula near Bahía Magdalena and 2 in the Gulf of California, we investigated parasitoid-host physiological responses (fatty acid and oxidative stress indicators) of the subtropical krill Nyctiphanes simplex infected with the ciliate P. brintoni. All life stages of P. brintoni were associated with opportunistic bacterial assemblages that have not been explicitly investigated in other Pseudocollinia species (P. beringensis, P. oregonensis, and P. similis). Parasitoid ciliates exclusively infected adult females, which showed increased lipid content during gonad development. As the infection progressed, omega-3 eicosapentaenoic and docosahexaenoic fatty acids, which may act as energy sources to produce high numbers of ciliate transmission stages, were quickly depleted. Antioxidant enzymes, components of the crustacean defense system, varied throughout infection, but without inhibiting Pseudocollinia infection, i.e. higher levels of lipid oxidative damage were detected in late stages of infection. The ineffective response of the krill antioxidant defense system against histophagous ciliates and the bacteria associated with the ciliates suggests that Pseudocollinia ciliates are functionally analogous to krill predators and may have a strong influence on the population dynamics of krill. PMID:26503777

  2. 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

  3. 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. PMID:26500226

  4. 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

  5. Interaction of the core fragments of the LL-37 host defense peptide with actin

    PubMed Central

    Sol, Asaf; Wang, Guangshun; Blotnick, Edna; Golla, Radha; Muhlrad, Andras

    2015-01-01

    Host defense peptides are effector molecules of the innate immunity that possess antimicrobial and health-promoting properties. Due to their potential therapeutic activities, host defense peptides are being explored as alternatives for antibiotics. The human LL-37 and its shorter, cost-effective, bactericidal core peptide derivates have been suggested for their therapeutic potential. Bacteria evade host defense peptides by proteolytic inactivation. Actin released from necrotized cells and abundant in infected sites was shown to bind and protect LL-37 from microbial proteolytic degradation, and to enable the peptide’s antimicrobial action despite the presence of the proteases. Here, we characterized the interactions of the 10–13 residues long LL-37 core peptides with actin. We show that the LL-37 core peptides associate with actin with a lower affinity than that of LL-37. Their association with actin, which is very ionic strength sensitive, is mainly based on electrostatic interactions. Likewise, the antimicrobial activity against Escherichia coli of the minimal antimicrobial peptide KR-12 but not FK-13 nor LL-37 is also very sensitive to salts. In addition, the antimicrobial activity of the FK-13 core peptide is protected by actin against the tested bacterial proteases in a similar manner to that of LL-37, supporting its potential for therapeutic use. PMID:26726303

  6. 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. PMID:25892682

  7. Laboratory Investigations Reveal that Harmonia axyridis (Coleoptera: Coccinellidae) Is a Poor Host for Dinocampus coccinellae (Hymenoptera: Braconidae) in Brazil

    PubMed Central

    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. PMID:27324582

  8. 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. PMID:27324582

  9. Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission

    PubMed Central

    Chauvin, Alain; Moreau, Emmanuelle; Bonnet, Sarah; Plantard, Olivier; Malandrin, Laurence

    2009-01-01

    Babesia, the causal agent of babesiosis, are tick-borne apicomplexan protozoa. True babesiae (Babesia genus sensu stricto) are biologically characterized by direct development in erythrocytes and by transovarial transmission in the tick. A large number of true Babesia species have been described in various vertebrate and tick hosts. This review presents the genus then discusses specific adaptations of Babesia spp. to their hosts to achieve efficient transmission. The main adaptations lead to long-lasting interactions which result in the induction of two reservoirs: in the vertebrate host during low long-term parasitemia and throughout the life cycle of the tick host as a result of transovarial and transstadial transmission. The molecular bases of these adaptations in vertebrate hosts are partially known but few of the tick-host interaction mechanisms have been elucidated. PMID:19379662

  10. Cohabitation in the intestine: interactions between helminth parasites, bacterial microbiota and host immunity

    PubMed Central

    Reynolds, Lisa A.; Finlay, B. Brett; Maizels, Rick M.

    2015-01-01

    Both intestinal helminth parasites and certain bacterial microbiota species have been credited with strong immunomodulatory effects. Recent studies have 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 affects helminth colonisation 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 between intestinal microbes, helminth parasites and the host immune system will allow for a more holistic approach when using pro-, pre-, synbiotics, antibiotics and anthelmintics, and when designing treatments for autoimmune and allergic conditions. PMID:26477048

  11. Update on host-pathogen interactions in cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Frey, Nina; Hartl, Dominik

    2016-12-01

    Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease. PMID:26905568

  12. MicroRNAs in the Host-Apicomplexan Parasites Interactions: A Review of Immunopathological Aspects

    PubMed Central

    Judice, Carla C.; Bourgard, Catarina; Kayano, Ana C. A. V.; Albrecht, Letusa; Costa, Fabio T. M.

    2016-01-01

    MicroRNAs (miRNAs), a class of small non-coding regulatory RNAs, have been detected in a variety of organisms ranging from ancient unicellular eukaryotes to mammals. They have been associated with numerous molecular mechanisms involving developmental, physiological and pathological changes of cells and tissues. Despite the fact that miRNA-silencing mechanisms appear to be absent in some Apicomplexan species, an increasing number of studies have reported a role for miRNAs in host-parasite interactions. Host miRNA expression can change following parasite infection and the consequences can lead, for instance, to parasite clearance. In this context, the immune system signaling appears to have a crucial role. PMID:26870701

  13. 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. PMID:26477048

  14. 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. PMID:26936760

  15. 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

  16. Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms

    NASA Astrophysics Data System (ADS)

    Puckett, James G.; Ni, Rui; Ouellette, Nicholas T.

    2015-06-01

    The macroscopic emergent behavior of social animal groups is a classic example of dynamical self-organization, and is thought to arise from the local interactions between individuals. Determining these interactions from empirical data sets of real animal groups, however, is challenging. Using multicamera imaging and tracking, we studied the motion of individual flying midges in laboratory mating swarms. By performing a time-frequency analysis of the midge trajectories, we show that the midge behavior can be segmented into two distinct modes: one that is independent and composed of low-frequency maneuvers, and one that consists of higher-frequency nearly harmonic oscillations conducted in synchrony with another midge. We characterize these pairwise interactions, and make a hypothesis as to their biological function.

  17. Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms.

    PubMed

    Puckett, James G; Ni, Rui; Ouellette, Nicholas T

    2015-06-26

    The macroscopic emergent behavior of social animal groups is a classic example of dynamical self-organization, and is thought to arise from the local interactions between individuals. Determining these interactions from empirical data sets of real animal groups, however, is challenging. Using multicamera imaging and tracking, we studied the motion of individual flying midges in laboratory mating swarms. By performing a time-frequency analysis of the midge trajectories, we show that the midge behavior can be segmented into two distinct modes: one that is independent and composed of low-frequency maneuvers, and one that consists of higher-frequency nearly harmonic oscillations conducted in synchrony with another midge. We characterize these pairwise interactions, and make a hypothesis as to their biological function. PMID:26197145

  18. 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

  19. A review on computational systems biology of pathogen-host interactions.

    PubMed

    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

  20. The Genome of Spraguea lophii and the Basis of Host-Microsporidian Interactions

    PubMed Central

    Campbell, Scott E.; Williams, Tom A.; Yousuf, Asim; Soanes, Darren M.; Paszkiewicz, Konrad H.; Williams, Bryony A. P.

    2013-01-01

    Microsporidia are obligate intracellular parasites with the smallest known eukaryotic genomes. Although they are increasingly recognized as economically and medically important parasites, the molecular basis of microsporidian pathogenicity is almost completely unknown and no genetic manipulation system is currently available. The fish-infecting microsporidian Spraguea lophii shows one of the most striking host cell manipulations known for these parasites, converting host nervous tissue into swollen spore factories known as xenomas. In order to investigate the basis of these interactions between microsporidian and host, we sequenced and analyzed the S. lophii genome. Although, like other microsporidia, S. lophii has lost many of the protein families typical of model eukaryotes, we identified a number of gene family expansions including a family of leucine-rich repeat proteins that may represent pathogenicity factors. Building on our comparative genomic analyses, we exploited the large numbers of spores that can be obtained from xenomas to identify potential effector proteins experimentally. We used complex-mix proteomics to identify proteins released by the parasite upon germination, resulting in the first experimental isolation of putative secreted effector proteins in a microsporidian. Many of these proteins are not related to characterized pathogenicity factors or indeed any other sequences from outside the Microsporidia. However, two of the secreted proteins are members of a family of RICIN B-lectin-like proteins broadly conserved across the phylum. These proteins form syntenic clusters arising from tandem duplications in several microsporidian genomes and may represent a novel family of conserved effector proteins. These computational and experimental analyses establish S. lophii as an attractive model system for understanding the evolution of host-parasite interactions in microsporidia and suggest an important role for lineage-specific innovations and fast

  1. 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

  2. The ecology, evolution, impacts and management of host-parasite interactions of marine molluscs.

    PubMed

    Coen, Loren D; Bishop, Melanie J

    2015-10-01

    Molluscs are economically and ecologically important components of aquatic ecosystems. In addition to supporting valuable aquaculture and wild-harvest industries, their populations determine the structure of benthic communities, cycling of nutrients, serve as prey resources for higher trophic levels and, in some instances, stabilize shorelines and maintain water quality. This paper reviews existing knowledge of the ecology of host-parasite interactions involving marine molluscs, with a focus on gastropods and bivalves. It considers the ecological and evolutionary impacts of molluscan parasites on their hosts and vice versa, and on the communities and ecosystems in which they are a part, as well as disease management and its ecological impacts. An increasing number of case studies show that disease can have important effects on marine molluscs, their ecological interactions and ecosystem services, at spatial scales from centimeters to thousands of kilometers and timescales ranging from hours to years. In some instances the cascading indirect effects arising from parasitic infection of molluscs extend well beyond the temporal and spatial scales at which molluscs are affected by disease. In addition to the direct effects of molluscan disease, there can be large indirect impacts on marine environments resulting from strategies, such as introduction of non-native species and selective breeding for disease resistance, put in place to manage disease. Much of our understanding of impacts of molluscan diseases on the marine environment has been derived from just a handful of intensively studied marine parasite-host systems, namely gastropod-trematode, cockle-trematode, and oyster-protistan interactions. Understanding molluscan host-parasite dynamics is of growing importance because: (1) expanding aquaculture; (2) current and future climate change; (3) movement of non-native species; and (4) coastal development are modifying molluscan disease dynamics, ultimately leading to

  3. Facilitating guest transport in clathrate hydrates by tuning guest-host interactions

    NASA Astrophysics Data System (ADS)

    Moudrakovski, Igor L.; Udachin, Konstantin A.; Alavi, Saman; Ratcliffe, Christopher I.; Ripmeester, John A.

    2015-02-01

    The understanding and eventual control of guest molecule transport in gas hydrates is of central importance for the efficient synthesis and processing of these materials for applications in the storage, separation, and sequestration of gases and natural gas production. Previously, some links have been established between dynamics of the host water molecules and guest-host hydrogen bonding interactions, but direct observation of transport in the form of cage-to-cage guest diffusion is still lacking. Recent calculations have suggested that pairs of different guest molecules in neighboring cages can affect guest-host hydrogen bonding and, therefore, defect injection and water lattice motions. We have chosen two sets of hydrate guest pairs, tetrahydrofuran (THF)-CO2 and isobutane-CO2, that are predicted to enhance or to diminish guest-host hydrogen bonding interactions as compared to those in pure CO2 hydrate and we have studied guest dynamics in each using 13C nuclear magnetic resonance (NMR) methods. In addition, we have obtained the crystal structure of the THF-CO2 sII hydrate using the combined single crystal X-ray diffraction and 13C NMR powder pattern data and have performed molecular dynamics-simulation of the CO2 dynamics. The NMR powder line shape studies confirm the enhanced and delayed dynamics for the THF and isobutane containing hydrates, respectively, as compared to those in the CO2 hydrate. In addition, from line shape studies and 2D exchange spectroscopy NMR, we observe cage-to-cage exchange of CO2 molecules in the THF-CO2 hydrate, but not in the other hydrates studied. We conclude that the relatively rapid intercage guest dynamics are the result of synergistic guest A-host water-guest B interactions, thus allowing tuning of the guest transport properties in the hydrates by choice of the appropriate guest molecules. Our experimental value for inter-cage hopping is slower by a factor of 106 than a published calculated value.

  4. Facilitating guest transport in clathrate hydrates by tuning guest-host interactions

    SciTech Connect

    Moudrakovski, Igor L.; Udachin, Konstantin A.; Ratcliffe, Christopher I.; Alavi, Saman; Ripmeester, John A.

    2015-02-21

    The understanding and eventual control of guest molecule transport in gas hydrates is of central importance for the efficient synthesis and processing of these materials for applications in the storage, separation, and sequestration of gases and natural gas production. Previously, some links have been established between dynamics of the host water molecules and guest-host hydrogen bonding interactions, but direct observation of transport in the form of cage-to-cage guest diffusion is still lacking. Recent calculations have suggested that pairs of different guest molecules in neighboring cages can affect guest-host hydrogen bonding and, therefore, defect injection and water lattice motions. We have chosen two sets of hydrate guest pairs, tetrahydrofuran (THF)-CO{sub 2} and isobutane-CO{sub 2}, that are predicted to enhance or to diminish guest–host hydrogen bonding interactions as compared to those in pure CO{sub 2} hydrate and we have studied guest dynamics in each using {sup 13}C nuclear magnetic resonance (NMR) methods. In addition, we have obtained the crystal structure of the THF-CO{sub 2} sII hydrate using the combined single crystal X-ray diffraction and {sup 13}C NMR powder pattern data and have performed molecular dynamics-simulation of the CO{sub 2} dynamics. The NMR powder line shape studies confirm the enhanced and delayed dynamics for the THF and isobutane containing hydrates, respectively, as compared to those in the CO{sub 2} hydrate. In addition, from line shape studies and 2D exchange spectroscopy NMR, we observe cage-to-cage exchange of CO{sub 2} molecules in the THF-CO{sub 2} hydrate, but not in the other hydrates studied. We conclude that the relatively rapid intercage guest dynamics are the result of synergistic guest A–host water–guest B interactions, thus allowing tuning of the guest transport properties in the hydrates by choice of the appropriate guest molecules. Our experimental value for inter-cage hopping is slower by a factor of 10

  5. Facilitating guest transport in clathrate hydrates by tuning guest-host interactions.

    PubMed

    Moudrakovski, Igor L; Udachin, Konstantin A; Alavi, Saman; Ratcliffe, Christopher I; Ripmeester, John A

    2015-02-21

    The understanding and eventual control of guest molecule transport in gas hydrates is of central importance for the efficient synthesis and processing of these materials for applications in the storage, separation, and sequestration of gases and natural gas production. Previously, some links have been established between dynamics of the host water molecules and guest-host hydrogen bonding interactions, but direct observation of transport in the form of cage-to-cage guest diffusion is still lacking. Recent calculations have suggested that pairs of different guest molecules in neighboring cages can affect guest-host hydrogen bonding and, therefore, defect injection and water lattice motions. We have chosen two sets of hydrate guest pairs, tetrahydrofuran (THF)-CO2 and isobutane-CO2, that are predicted to enhance or to diminish guest-host hydrogen bonding interactions as compared to those in pure CO2 hydrate and we have studied guest dynamics in each using (13)C nuclear magnetic resonance (NMR) methods. In addition, we have obtained the crystal structure of the THF-CO2 sII hydrate using the combined single crystal X-ray diffraction and (13)C NMR powder pattern data and have performed molecular dynamics-simulation of the CO2 dynamics. The NMR powder line shape studies confirm the enhanced and delayed dynamics for the THF and isobutane containing hydrates, respectively, as compared to those in the CO2 hydrate. In addition, from line shape studies and 2D exchange spectroscopy NMR, we observe cage-to-cage exchange of CO2 molecules in the THF-CO2 hydrate, but not in the other hydrates studied. We conclude that the relatively rapid intercage guest dynamics are the result of synergistic guest A-host water-guest B interactions, thus allowing tuning of the guest transport properties in the hydrates by choice of the appropriate guest molecules. Our experimental value for inter-cage hopping is slower by a factor of 10(6) than a published calculated value. PMID:25702022

  6. Revealing Significant Learning Moments with Interactive Whiteboards in Mathematics

    ERIC Educational Resources Information Center

    Bruce, Catherine D.; McPherson, Richard; Sabeti, Farhad Mordy; Flynn, Tara

    2011-01-01

    The aim of this study was to identify when and how the interactive whiteboard (IWB) functioned as a productive tool that impacted student learning in mathematics. Using video data, field notes, and interview transcripts from 1 school year in two optimal case study classrooms, we were able to examine the unique opportunities afforded by the size of…

  7. Fish introductions reveal the temperature dependence of species interactions.

    PubMed

    Hein, Catherine L; Öhlund, Gunnar; Englund, Göran

    2014-01-22

    A major area of current research is to understand how climate change will impact species interactions and ultimately biodiversity. A variety of environmental conditions are rapidly changing owing to climate warming, and these conditions often affect both the strength and outcome of species interactions. We used fish distributions and replicated fish introductions to investigate environmental conditions influencing the coexistence of two fishes in Swedish lakes: brown trout (Salmo trutta) and pike (Esox lucius). A logistic regression model of brown trout and pike coexistence showed that these species coexist in large lakes (more than 4.5 km(2)), but not in small, warm lakes (annual air temperature more than 0.9-1.5°C). We then explored how climate change will alter coexistence by substituting climate scenarios for 2091-2100 into our model. The model predicts that brown trout will be extirpated from approximately half of the lakes where they presently coexist with pike and from nearly all 9100 lakes where pike are predicted to invade. Context dependency was critical for understanding pike-brown trout interactions, and, given the widespread occurrence of context-dependent species interactions, this aspect will probably be critical for accurately predicting climate impacts on biodiversity. PMID:24307673

  8. Fish introductions reveal the temperature dependence of species interactions

    PubMed Central

    Hein, Catherine L.; Öhlund, Gunnar; Englund, Göran

    2014-01-01

    A major area of current research is to understand how climate change will impact species interactions and ultimately biodiversity. A variety of environmental conditions are rapidly changing owing to climate warming, and these conditions often affect both the strength and outcome of species interactions. We used fish distributions and replicated fish introductions to investigate environmental conditions influencing the coexistence of two fishes in Swedish lakes: brown trout (Salmo trutta) and pike (Esox lucius). A logistic regression model of brown trout and pike coexistence showed that these species coexist in large lakes (more than 4.5 km2), but not in small, warm lakes (annual air temperature more than 0.9–1.5°C). We then explored how climate change will alter coexistence by substituting climate scenarios for 2091–2100 into our model. The model predicts that brown trout will be extirpated from approximately half of the lakes where they presently coexist with pike and from nearly all 9100 lakes where pike are predicted to invade. Context dependency was critical for understanding pike–brown trout interactions, and, given the widespread occurrence of context-dependent species interactions, this aspect will probably be critical for accurately predicting climate impacts on biodiversity. PMID:24307673

  9. Genetic characterization of a novel wheat-Stagonospora nodorum host-selective toxin interaction and it role in disease susceptibility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent work suggests that the S. nodorum-wheat pathosystem is controlled by host-selective toxins (HSTs) (SnToxA, SnTox1, SnTox2) that interact directly or indirectly with dominant host genes (Tsn1, Snn1, Snn2) to induce disease. Here we describe and characterize a novel HST designated SnTox3, and ...

  10. 3D nitrogen-doped graphene/β-cyclodextrin: host-guest interactions for electrochemical sensing

    NASA Astrophysics Data System (ADS)

    Liu, Jilun; Leng, Xuanye; Xiao, Yao; Hu, Chengguo; Fu, Lei

    2015-07-01

    Host-guest interactions, especially those between cyclodextrins (CDs, including α-, β- and γ-CD) and various guest molecules, exhibit a very high supramolecular recognition ability. Thus, they have received considerable attention in different fields. These specific interactions between host and guest molecules are promising for biosensing and clinical detection. However, there is a lack of an ideal electrode substrate for CDs to increase their performance in electrochemical sensing. Herein, we propose a new 3D nitrogen-doped graphene (3D-NG) based electrochemical sensor, taking advantage of the superior sensitivity of host-guest interactions. Our 3D-NG was fabricated by a template-directed chemical vapour deposition (CVD) method, and it showed a large specific surface area, a high capacity for biomolecules and a high electron transfer efficiency. Thus, for the first time, we took 3D-NG as an electrode substrate for β-CD to establish a new type of biosensor. Using dopamine (DA) and acetaminophen (APAP) as representative guest molecules, our 3D-NG/β-CD biosensor shows extremely high sensitivities (5468.6 μA mM-1 cm-2 and 2419.2 μA mM-1 cm-2, respectively), which are significantly higher than those reported in most previous studies. The stable adsorption of β-CD on 3D-NG indicates potential applications in clinical detection and medical testing.Host-guest interactions, especially those between cyclodextrins (CDs, including α-, β- and γ-CD) and various guest molecules, exhibit a very high supramolecular recognition ability. Thus, they have received considerable attention in different fields. These specific interactions between host and guest molecules are promising for biosensing and clinical detection. However, there is a lack of an ideal electrode substrate for CDs to increase their performance in electrochemical sensing. Herein, we propose a new 3D nitrogen-doped graphene (3D-NG) based electrochemical sensor, taking advantage of the superior sensitivity

  11. Role of Protein Glycosylation in Candida parapsilosis Cell Wall Integrity and Host Interaction

    PubMed Central

    Pérez-García, Luis A.; Csonka, Katalin; Flores-Carreón, Arturo; Estrada-Mata, Eine; Mellado-Mojica, Erika; Németh, Tibor; López-Ramírez, Luz A.; Toth, Renata; López, Mercedes G.; Vizler, Csaba; Marton, Annamaria; Tóth, Adél; Nosanchuk, Joshua D.; Gácser, Attila; Mora-Montes, Héctor M.

    2016-01-01

    Candida parapsilosis is an important, emerging opportunistic fungal pathogen. Highly mannosylated fungal cell wall proteins are initial contact points with host immune systems. In Candida albicans, Och1 is a Golgi α1,6-mannosyltransferase that plays a key role in the elaboration of the N-linked mannan outer chain. Here, we disrupted C. parapsilosis OCH1 to gain insights into the contribution of N-linked mannosylation to cell fitness and to interactions with immune cells. Loss of Och1 in C. parapsilosis resulted in cellular aggregation, failure of morphogenesis, enhanced susceptibility to cell wall perturbing agents and defects in wall composition. We removed the cell wall O-linked mannans by β-elimination, and assessed the relevance of mannans during interaction with human monocytes. Results indicated that O-linked mannans are important for IL-1β stimulation in a dectin-1 and TLR4-dependent pathway; whereas both, N- and O-linked mannans are equally important ligands for TNFα and IL-6 stimulation, but neither is involved in IL-10 production. Furthermore, mice infected with C. parapsilosis och1Δ null mutant cells had significantly lower fungal burdens compared to wild-type (WT)-challenged counterparts. Therefore, our data are the first to demonstrate that C. parapsilosis N- and O-linked mannans have different roles in host interactions than those reported for C. albicans. PMID:27014229

  12. Host-Pathogen Interaction Profiling Using Self-Assembling Human Protein Arrays

    PubMed Central

    Yu, Xiaobo; Decker, Kimberly B.; Barker, Kristi; Neunuebel, M. Ramona; Saul, Justin; Graves, Morgan; Westcott, Nathan; Hang, Howard; LaBaer, Joshua; Qiu, Ji; Machner, Matthias P.

    2015-01-01

    Host-pathogen protein interactions are fundamental to every microbial infection, yet their identification has remained challenging due to the lack of simple detection tools that avoid abundance biases while providing an open format for experimental modifications. Here, we applied the Nucleic Acid-Programmable Protein Array and a HaloTag-Halo ligand detection system to determine the interaction network of Legionella pneumophila effectors (SidM and LidA) with 10,000 unique human proteins. We identified known targets of these L. pneumophila proteins and potentially novel interaction candidates. In addition, we applied our Click chemistry-based NAPPA platform to identify the substrates for SidM, an effector with an adenylyl transferase domain that catalyzes AMPylation (adenylylation), the covalent addition of adenosine monophosphate (AMP). We confirmed a subset of the novel SidM and LidA targets in independent in vitro pull-down and in vivo cell-based assays, and provided further insight into how these effectors may discriminate between different host Rab GTPases. Our method circumvents the purification of thousands of human and pathogen proteins, and does not require antibodies against or pre-labeling of query proteins. This system is amenable to high-throughput analysis of effectors from a wide variety of human pathogens that may bind to and/or post-translationally modify targets within the human proteome. PMID:25739981

  13. Dynamic changes in host-virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta).

    PubMed

    Manfredini, Fabio; Shoemaker, DeWayne; Grozinger, Christina M

    2016-01-01

    The dynamics of host-parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host-viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host-parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV-1 and SINV-2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV-2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations. PMID:26811788

  14. Multilocus sequence typing of Mycoplasma bovis reveals host-specific genotypes in cattle versus bison.

    PubMed

    Register, Karen B; Thole, Luke; Rosenbush, Ricardo F; Minion, F Chris

    2015-01-30

    Mycoplasma bovis is a primary agent of mastitis, pneumonia and arthritis in cattle and the bacterium most frequently isolated from the polymicrobial syndrome known as bovine respiratory disease complex. Recently, M. bovis has emerged as a significant health problem in bison, causing necrotic pharyngitis, pneumonia, dystocia and abortion. Whether isolates from cattle and bison comprise genetically distinct populations is unknown. This study describes the development of a highly discriminatory multilocus sequencing typing (MLST) method for M. bovis and its use to investigate the population structure of the bacterium. Genome sequences from six M. bovis isolates were used for selection of gene targets. Seven of 44 housekeeping genes initially evaluated were selected as targets on the basis of sequence variability and distribution within the genome. For each gene target sequence, four to seven alleles could be distinguished that collectively define 32 sequence types (STs) from a collection of 94 cattle isolates and 42 bison isolates. A phylogeny based on concatenated target gene sequences of each isolate revealed that bison isolates are genetically distinct from strains that infect cattle, suggesting recent disease outbreaks in bison may be due to the emergence of unique genetic variants. No correlation was found between ST and disease presentation or geographic origin. MLST data reported here were used to populate a newly created and publicly available, curated database to which researchers can contribute. The MLST scheme and database provide novel tools for exploring the population structure of M. bovis and tracking the evolution and spread of strains. PMID:25433454

  15. A responsive supramolecular polymer formed by orthogonal metal-coordination and cryptand-based host-guest interaction.

    PubMed

    Wei, Peifa; Xia, Binyuan; Zhang, Yanyan; Yu, Yihua; Yan, Xuzhou

    2014-04-18

    Herein, a cation responsive linear supramolecular polymer was constructed in an orthogonal fashion by unifying the themes of coordination-driven self-assembly and cryptand-based host-guest interaction. PMID:24609282

  16. The influence of early neutrophil-Leishmania interactions on the host immune response to infection

    PubMed Central

    Ribeiro-Gomes, Flavia L.; Sacks, David

    2012-01-01

    Neutrophils are the first cells recruited to the dermal site of Leishmania infection following injection by needle or sand fly bite. The role of neutrophils in either promoting or suppressing host immunity remains controversial. We discuss the events driving neutrophil recruitment, their interaction with the parasite and apoptotic fate, and the nature of their encounters with other innate cells. We suggest that the influence of the neutrophil response on infection outcome critically depends on the timing of their recruitment and the tissue environment in which it occurs. PMID:22919650

  17. Gibberellins in Penicillium strains: Challenges for endophyte-plant host interactions under salinity stress.

    PubMed

    Leitão, Ana Lúcia; Enguita, Francisco J

    2016-02-01

    The genus Penicillium is one of the most versatile "mycofactories", comprising some species able to produce gibberellins, bioactive compounds that can modulate plant growth and development. Although plants have the ability to synthesize gibberellins, their levels are lower when plants are under salinity stress. It has been recognized that detrimental abiotic conditions, such as saline stress, have negative effects on plants, being the availability of bioactive gibberellins a critical factor for their growth under this conditions. This review summarizes the interplay existing between endophytic Penicillium strains and plant host interactions, with focus on bioactive gibberellins production as a fungal response that allows plants to overcome salinity stress. PMID:26805614

  18. Schistosomes: the road from host-parasite interactions to vaccines in clinical trials.

    PubMed

    Capron, André; Riveau, Gilles; Capron, Monique; Trottein, François

    2005-03-01

    Insights over recent years into the interactions between helminths, including schistosomes, and the immune system have generated new concepts in immunology and significant advances in vaccine strategies. Here, we report recent advances that substantially increase our understanding of the nature of the host innate and adaptive responses to schistosomes and on strategies elaborated by the parasite to manipulate such responses. We also describe the long road that has allowed us to move from the identification of an anti-schistosome vaccine candidate, a 28kDa glutathione-S-transferase, to its recent evaluation in human clinical trials. PMID:15734662

  19. Intestinal IgA production and its role in host-microbe interaction

    PubMed Central

    Gutzeit, Cindy; Magri, Giuliana; Cerutti, Andrea

    2014-01-01

    Summary Complex and diverse communities of bacteria establish mutualistic and symbiotic relationships with the gut after birth. The intestinal immune system responds to bacterial colonization by acquiring a state of hypo-responsiveness against commensals and active readiness against pathogens. The resulting homeostatic balance involves a continuous dialog between the microbiota and lymphocytes with the intermediation of epithelial and dendritic cells. This dialog causes massive production of immunoglobulin A (IgA), a non-inflammatory antibody specialized in mucosal protection. Here, we discuss recent advances on the regulation of intestinal IgA responses and their role in host-microbe interaction. PMID:24942683

  20. Dual-responsive colloidal microcapsules based on host-guest interaction on solid templates.

    PubMed

    Li, Guangyu; Dong, Zhirui; Zhu, Yuting; Tong, Weijun; Gao, Changyou

    2016-08-01

    Colloidal microcapsules (MCs) have received considerable attention in the fields of microencapsulation, drug delivery as well as microreactors due to their unique nanoparticles-composed structure. In this study, dual-responsive colloidal MCs based on host-guest interaction were successfully fabricated via a layer-by-layer assembly method on sacrificial solid templates. Ferrocene-modified polyethylenimine (PEI-Fc) and cyclodextrin-modified polystyrene nanoparticles (PS-CD NPs) were used as building blocks for assembly. The colloidal MCs could be disassembled into nano-components upon addition of competitive adamantane (Ad) molecules or in the solution with a pH lower than 4. PMID:27175830

  1. Recombinant Ranaviruses for Studying Evolution of Host-Pathogen Interactions in Ectothermic Vertebrates.

    PubMed

    Robert, Jacques; Jancovich, James K

    2016-01-01

    Ranaviruses (Iridoviridae) are large DNA viruses that are causing emerging infectious diseases at an alarming rate in both wild and captive cold blood vertebrate species all over the world. Although the general biology of these viruses that presents some similarities with poxvirus is characterized, many aspects of their replication cycles, host cell interactions and evolution still remain largely unclear, especially in vivo. Over several years, strategies to generate site-specific ranavirus recombinant, either expressing fluorescent reporter genes or deficient for particular viral genes, have been developed. We review here these strategies, the main ranavirus recombinants characterized and their usefulness for in vitro and in vivo studies. PMID:27399758

  2. Intestinal IgA production and its role in host-microbe interaction.

    PubMed

    Gutzeit, Cindy; Magri, Giuliana; Cerutti, Andrea

    2014-07-01

    Complex and diverse communities of bacteria establish mutualistic and symbiotic relationships with the gut after birth. The intestinal immune system responds to bacterial colonization by acquiring a state of hypo-responsiveness against commensals and active readiness against pathogens. The resulting homeostatic balance involves a continuous dialog between the microbiota and lymphocytes with the intermediation of epithelial and dendritic cells. This dialog causes massive production of immunoglobulin A (IgA), a non-inflammatory antibody specialized in mucosal protection. Here, we discuss recent advances on the regulation of intestinal IgA responses and their role in host-microbe interaction. PMID:24942683

  3. Joint fitting reveals hidden interactions in tumor growth.

    PubMed

    Barberis, L; Pasquale, M A; Condat, C A

    2015-01-21

    Tumor growth is often the result of the simultaneous development of two or more cancer cell populations. Crucial to the system evolution are the interactions between these populations. To obtain information about these interactions we apply the recently developed vector universality (VUN) formalism to various instances of competition between tumor populations. The formalism allows us (a) to quantify the growth mechanisms of a HeLa cell colony, describing the phenotype switching responsible for its fast expansion, (b) to reliably reconstruct the evolution of the necrotic and viable fractions in both in vitro and in vivo tumors using data for the time dependences of the total masses alone, and (c) to show how the shedding of cells leading to subspheroid formation is beneficial to both the spheroid and subspheroid populations, suggesting that shedding is a strong positive influence on cancer dissemination. PMID:25451531

  4. Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure

    PubMed Central

    Lewis, Amanda L.; Desa, Nolan; Hansen, Elizabeth E.; Knirel, Yuriy A.; Gordon, Jeffrey I.; Gagneux, Pascal; Nizet, Victor; Varki, Ajit

    2009-01-01

    Sialic acids (Sias) are nonulosonic acid (NulO) sugars prominently displayed on vertebrate cells and occasionally mimicked by bacterial pathogens using homologous biosynthetic pathways. It has been suggested that Sias were an animal innovation and later emerged in pathogens by convergent evolution or horizontal gene transfer. To better illuminate the evolutionary processes underlying the phenomenon of Sia molecular mimicry, we performed phylogenomic analyses of biosynthetic pathways for Sias and related higher sugars derived from 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids. Examination of ≈1,000 sequenced microbial genomes indicated that such biosynthetic pathways are far more widely distributed than previously realized. Phylogenetic analysis, validated by targeted biochemistry, was used to predict NulO types (i.e., neuraminic, legionaminic, or pseudaminic acids) expressed by various organisms. This approach uncovered previously unreported occurrences of Sia pathways in pathogenic and symbiotic bacteria and identified at least one instance in which a human archaeal symbiont tentatively reported to express Sias in fact expressed the related pseudaminic acid structure. Evaluation of targeted phylogenies and protein domain organization revealed that the “unique” Sia biosynthetic pathway of animals was instead a much more ancient innovation. Pathway phylogenies suggest that bacterial pathogens may have acquired Sia expression via adaptation of pathways for legionaminic acid biosynthesis, one of at least 3 evolutionary paths for de novo Sia synthesis. Together, these data indicate that some of the long-standing paradigms in Sia biology should be reconsidered in a wider evolutionary context of the extended family of NulO sugars. PMID:19666579

  5. Graphlet-based edge clustering reveals pathogen-interacting proteins

    PubMed Central

    Solava, R. W.; Michaels, R. P.; Milenković, T.

    2012-01-01

    Motivation: Prediction of protein function from protein interaction networks has received attention in the post-genomic era. A popular strategy has been to cluster the network into functionally coherent groups of proteins and assign the entire cluster with a function based on functions of its annotated members. Traditionally, network research has focused on clustering of nodes. However, clustering of edges may be preferred: nodes belong to multiple functional groups, but clustering of nodes typically cannot capture the group overlap, while clustering of edges can. Clustering of adjacent edges that share many neighbors was proposed recently, outperforming different node clustering methods. However, since some biological processes can have characteristic ‘signatures’ throughout the network, not just locally, it may be of interest to consider edges that are not necessarily adjacent. Results: We design a sensitive measure of the ‘topological similarity’ of edges that can deal with edges that are not necessarily adjacent. We cluster edges that are similar according to our measure in different baker's yeast protein interaction networks, outperforming existing node and edge clustering approaches. We apply our approach to the human network to predict new pathogen-interacting proteins. This is important, since these proteins represent drug target candidates. Availability: Software executables are freely available upon request. Contact: tmilenko@nd.edu Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:22962470

  6. Impact Of Environmental Variation On Host Performance Differs With Pathogen Identity: Implications For Host-Pathogen Interactions In A Changing Climate

    PubMed Central

    Shikano, Ikkei; Cory, Jenny S.

    2015-01-01

    Specialist and generalist pathogens may exert different costs on their hosts; thereby altering the way hosts cope with environmental variation. We examined how pathogen-challenge alters the environmental conditions that maximize host performance by simultaneously varying temperature and nutrition (protein to carbohydrate ratio; P:C) after exposure to two baculoviruses; one that is specific to the cabbage looper, Trichoplusia ni (TnSNPV) and another that has a broad host range (AcMNPV). Virus-challenged larvae performed better on more protein-biased diets, primarily due to higher survival, whereas unchallenged larvae performed best on a balanced diet. The environmental conditions that maximized host performance differed with virus identity because TnSNPV-challenge inflicted fitness costs (reduced pupal weight and prolonged development) whereas AcMNPV-challenge did not. The performance of TnSNPV-challenged larvae rose with increasing P:C across all temperatures, whereas temperature modulated the optimal P:C in AcMNPV-challenged larvae (slightly protein-biased at 16 °C to increasingly higher P:C as temperature increased). Increasing temperature reduced pupal size, but only at more balanced P:C ratios, indicating that nutrition moderates the temperature-size rule. Our findings highlight the complex environmental interactions that can alter host performance after exposure to pathogens, which could impact the role of entomopathogens as regulators of insect populations in a changing climate. PMID:26477393

  7. Dandruff is associated with the conjoined interactions between host and microorganisms

    PubMed Central

    Xu, Zhijue; Wang, Zongxiu; Yuan, Chao; Liu, Xiaoping; Yang, Fang; Wang, Ting; Wang, Junling; Manabe, Kenji; Qin, Ou; Wang, Xuemin; Zhang, Yan; Zhang, Menghui

    2016-01-01

    Dandruff is an unpleasant scalp disorder common to human populations. In this study, we systematically investigated the intra- and inter-associations among dandruff, physiological conditions such as sebum of the scalp, host demographics such as gender, age and the region of the scalp, and the microorganisms on the scalp. We found that the physiological conditions were highly relevant to the host age and varied in different regions of the same scalp. The sebum quantity and water content were negatively correlated with the formation of dandruff and had significant relationships with the two dominant but reciprocally inhibited bacteria on the scalp (Propionibacterium and Staphylococcus). The dominant fungus (Malassezia species) displayed contrary roles in its contribution to the healthy scalp micro-environment. Bacteria and fungi didn’t show a close association with each other, but the intramembers were tightly linked. Bacteria had a stronger relationship with the severity of dandruff than fungi. Our results indicated that the severity of dandruff was closely associated with the interactions between the host and microorganisms. This study suggests that adjusting the balance of the bacteria on the scalp, particularly by enhancing Propionibacterium and suppressing Staphylococcus, might be a potential solution to lessen dandruff. PMID:27172459

  8. Phage-Host Interactions of Cheese-Making Lactic Acid Bacteria.

    PubMed

    Mahony, Jennifer; McDonnell, Brian; Casey, Eoghan; van Sinderen, Douwe

    2016-01-01

    Cheese production is a global biotechnological practice that is reliant on robust and technologically appropriate starter and adjunct starter cultures to acidify the milk and impart particular flavor and textural properties to specific cheeses. To this end, lactic acid bacteria, including Lactococcus lactis, Streptococcus thermophilus, and Lactobacillus and Leuconostoc spp., are routinely employed. However, these bacteria are susceptible to infection by (bacterio)phages. Over the past decade in particular, significant advances have been achieved in defining the receptor molecules presented by lactococcal host bacteria and in the structural analysis of corresponding phage-encoded receptor-binding proteins. These lactococcal model systems are expanding toward understanding phage-host interactions of other LAB species. Ultimately, such scientific efforts will uncover the mechanistic (dis)similarities among these phages and define how these phages recognize and infect their hosts. This review presents the current status of the LAB-phage interactome, highlighting the most recent and significant developments in this active research field. PMID:26735798

  9. Viral dark matter and virus–host interactions resolved from publicly available microbial genomes

    PubMed Central

    Roux, Simon; Hallam, Steven J; Woyke, Tanja; Sullivan, Matthew B

    2015-01-01

    The ecological importance of viruses is now widely recognized, yet our limited knowledge of viral sequence space and virus–host interactions precludes accurate prediction of their roles and impacts. In this study, we mined publicly available bacterial and archaeal genomic data sets to identify 12,498 high-confidence viral genomes linked to their microbial hosts. These data augment public data sets 10-fold, provide first viral sequences for 13 new bacterial phyla including ecologically abundant phyla, and help taxonomically identify 7–38% of ‘unknown’ sequence space in viromes. Genome- and network-based classification was largely consistent with accepted viral taxonomy and suggested that (i) 264 new viral genera were identified (doubling known genera) and (ii) cross-taxon genomic recombination is limited. Further analyses provided empirical data on extrachromosomal prophages and coinfection prevalences, as well as evaluation of in silico virus–host linkage predictions. Together these findings illustrate the value of mining viral signal from microbial genomes. DOI: http://dx.doi.org/10.7554/eLife.08490.001 PMID:26200428

  10. Fluorescence quenching in β-cyclodextrin vesicles: membrane confinement and host-guest interactions.

    PubMed

    Schibilla, Frauke; Stegemann, Linda; Strassert, Cristian A; Rizzo, Fabio; Ravoo, Bart Jan

    2016-02-01

    Fluorescent β-cyclodextrin vesicles (β-CDV) that display host cavities available for host-guest interactions at the vesicle surface were prepared by incorporation of the hydrophobic spirobifluorene-based dye 1 into the membrane of unilamellar vesicles. Fluorescence quenching of dye 1 was observed in the presence of different quenchers. Methyl viologen 2 does not quench dye 1 because it does not bind to β-CDV. 4-Nitrophenol 3 and 4-nitrophenol covalently connected to adamantane 4 quench the fluorescence of dye 1 in neutral solution, but by different mechanisms according to lifetime measurements. The quenching efficiency of 3 is pH dependent due to the presence of the phenolate form. Competition experiments with excess host and guest showed that 3 is likely to diffuse in and out of the membrane, while 4 forms an inclusion complex with β-CDV leading to close contact and efficient quenching. Our findings confirm that this dynamic supramolecular system is a versatile model to investigate quenching and recognition processes in bilayer membranes. PMID:26777315

  11. Brucella spp noncanonical LPS: structure, biosynthesis, and interaction with host immune system

    PubMed Central

    Cardoso, Patrícia Gomes; Macedo, Gilson Costa; Azevedo, Vasco; Oliveira, Sergio Costa

    2006-01-01

    Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and non-professional phagocytes, and cause abortion in domestic animals and undulant fever in humans. Several species are recognized within the genus Brucella and this classification is mainly based on the difference in pathogenicity and in host preference. Brucella strains may occur as either smooth or rough, expressing smooth LPS (S-LPS) or rough LPS (R-LPS) as major surface antigen. This bacterium possesses an unconventional non-endotoxic lipopolysaccharide that confers resistance to anti-microbial attacks and modulates the host immune response. The strains that are pathogenic for humans (B. abortus, B. suis, B. melitensis) carry a smooth LPS involved in the virulence of these bacteria. The LPS O-chain protects the bacteria from cellular cationic peptides, oxygen metabolites and complement-mediated lysis and it is a key molecule for Brucella survival and replication in the host. Here, we review i) Brucella LPS structure; ii) Brucella genome, iii) genes involved in LPS biosynthesis; iv) the interaction between LPS and innate immunity. PMID:16556309

  12. Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview

    PubMed Central

    Pinheiro, Roberta Olmo; de Souza Salles, Jorgenilce; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

    2011-01-01

    Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae–host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. PMID:21366421

  13. Hepatic tissue culture model for study of host-parasite interactions in alveolar echinococcosis.

    PubMed Central

    Jura, H; Bader, A; Hartmann, M; Maschek, H; Frosch, M

    1996-01-01

    An in vitro model for growth and differentiation of the metacestode tissue of the tapeworm Echinococcus multilocularis is described. This model simulates the organotropism of the parasite toward the liver of the intermediate host. In the presence of collagen-embedded primary hepatocytes from rats and humans, which can be kept in culture for 2 to 3 months, the parasitic vesicles grew by exogenous budding and multiplied about 12-fold within 3 weeks. In contrast, without the hepatocytes, the metacestodes rapidly degenerated. Development of protoscolices was seen only in the presence of rat hepatocytes but not in coculture of the metacestodes with hepatocytes of human origin, thus reflecting the in vivo situation during infection of rodents and in alveolar echinococcosis in humans. The experiments indicated that growth of the metacestodes and development of protoscolices depended on soluble low-molecular-weight factors released by the hepatocytes. The in vitro-grown metacestodes did not differ morphologically from the larvae found in infected intermediate hosts, and their infectivity was completely maintained. This report describes the first in vitro model of alveolar echinococcosis and will be the basis for future studies on host-parasite interactions of this important zoonosis. PMID:8751888

  14. Sating a Voracious Appetite: The Tidal Interaction of Close-in Planets with their Host Stars

    NASA Astrophysics Data System (ADS)

    Matsakos, Titos; Königl, Arieh

    2015-12-01

    Transit observations of the apparent angle between the stellar spin and the vector normal to the planetary orbital plane suggest that cool stars are preferably aligned systems even as hot stars exhibit a large range of obliquities. In addition, as was demonstrated recently by Mazeh et al., the distribution of planet periods as a function of mass exhibits a dearth of sub-Jupiter--mass planets at < 4 days periods, with the boundary of the sparsely populated region in phase space having a roughly conical shape. We suggest that both of these seemingly disparate features are manifestations of the tidal interaction between close-in planets and their host stars. We attribute the dichotomy in the obliquity properties to the effect of an early population of hot Jupiters that got stranded near the inner edge of a primordially misaligned protoplanetary disk and subsequently (on a timescale < 1 Gyr) ingested by the host star. The relative magnitudes of the stellar spin and planetary orbital angular momenta at the time of ingestion determined whether the hot Jupiter could realign the host; this did not happen in the case of hot stars because of inefficient magnetic braking and a comparatively high moment of inertia. We interpret the dearth of intermediate-mass planets at short periods by considering the tidal evolution of planets that arrive on highly eccentric orbits at later (> 1 Gyr) times and become circularized at radii of a few times the Roche limit.

  15. Dandruff is associated with the conjoined interactions between host and microorganisms.

    PubMed

    Xu, Zhijue; Wang, Zongxiu; Yuan, Chao; Liu, Xiaoping; Yang, Fang; Wang, Ting; Wang, Junling; Manabe, Kenji; Qin, Ou; Wang, Xuemin; Zhang, Yan; Zhang, Menghui

    2016-01-01

    Dandruff is an unpleasant scalp disorder common to human populations. In this study, we systematically investigated the intra- and inter-associations among dandruff, physiological conditions such as sebum of the scalp, host demographics such as gender, age and the region of the scalp, and the microorganisms on the scalp. We found that the physiological conditions were highly relevant to the host age and varied in different regions of the same scalp. The sebum quantity and water content were negatively correlated with the formation of dandruff and had significant relationships with the two dominant but reciprocally inhibited bacteria on the scalp (Propionibacterium and Staphylococcus). The dominant fungus (Malassezia species) displayed contrary roles in its contribution to the healthy scalp micro-environment. Bacteria and fungi didn't show a close association with each other, but the intramembers were tightly linked. Bacteria had a stronger relationship with the severity of dandruff than fungi. Our results indicated that the severity of dandruff was closely associated with the interactions between the host and microorganisms. This study suggests that adjusting the balance of the bacteria on the scalp, particularly by enhancing Propionibacterium and suppressing Staphylococcus, might be a potential solution to lessen dandruff. PMID:27172459

  16. Microarray analysis of gene expression in eastern oyster (Crassostrea virginica) reveals a novel combination of antimicrobial and oxidative stress host responses after dermo (Perkinsus marinus) challenge.

    PubMed

    Wang, Shaolin; Peatman, Eric; Liu, Hong; Bushek, David; Ford, Susan E; Kucuktas, Huseyin; Quilang, Jonas; Li, Ping; Wallace, Richard; Wang, Yongping; Guo, Ximing; Liu, Zhanjiang

    2010-12-01

    Dermo disease, caused by Perkinsus marinus, is one of the most severe diseases of eastern oysters, Crassostrea virginica. It causes serious mortalities in both wild and aquacultured oysters. Using existing expressed sequence tag (EST) resources, we developed a 12K in situ oligonucleotide microarray and used it for the analysis of gene expression profiles of oysters during the interactions between P. marinus and its oyster host. Significant gene expression regulation was found at day 30 post-challenge in the eastern oyster. Putative identities of the differentially expressed genes revealed a set of genes involved in several processes including putative antimicrobial defenses, pathogen recognition and uptake, anti-oxidation and apoptosis. Consistent with results obtained from previous, smaller-scale experiments, expression profiles revealed a large set of genes likely involved in an active mitigating response to oxidative stress and apoptosis induced by P. marinus. Additionally, a unique galectin from C. virginica, CvGal, which serves as a preferential receptor for P. marinus trophozoites, was found to be significantly down-regulated in gill tissue of oysters with both light and heavy infection, suggesting an attempt to control parasite uptake and proliferation in the later stages of infection. Potential histone-derived antimicrobial responses to P. marinus were also revealed in the gene expression profiles. PMID:20708691

  17. Real-Time Sensing of Enteropathogenic E. coli-Induced Effects on Epithelial Host Cell Height, Cell-Substrate Interactions, and Endocytic Processes by Infrared Surface Plasmon Spectroscopy

    PubMed Central

    Zlotkin-Rivkin, Efrat; Rund, David; Melamed-Book, Naomi; Zahavi, Eitan Erez; Perlson, Eran; Mercone, Silvana; Golosovsky, Michael; Davidov, Dan; Aroeti, Benjamin

    2013-01-01

    Enteropathogenic Escherichia coli (EPEC) is an important, generally non-invasive, bacterial pathogen that causes diarrhea in humans. The microbe infects mainly the enterocytes of the small intestine. Here we have applied our newly developed infrared surface plasmon resonance (IR-SPR) spectroscopy approach to study how EPEC infection affects epithelial host cells. The IR-SPR experiments showed that EPEC infection results in a robust reduction in the refractive index of the infected cells. Assisted by confocal and total internal reflection microscopy, we discovered that the microbe dilates the intercellular gaps and induces the appearance of fluid-phase-filled pinocytic vesicles in the lower basolateral regions of the host epithelial cells. Partial cell detachment from the underlying substratum was also observed. Finally, the waveguide mode observed by our IR-SPR analyses showed that EPEC infection decreases the host cell's height to some extent. Together, these observations reveal novel impacts of the pathogen on the host cell architecture and endocytic functions. We suggest that these changes may induce the infiltration of a watery environment into the host cell, and potentially lead to failure of the epithelium barrier functions. Our findings also indicate the great potential of the label-free IR-SPR approach to study the dynamics of host-pathogen interactions with high spatiotemporal sensitivity. PMID:24194932

  18. Virus versus Host Plant MicroRNAs: Who Determines the Outcome of the Interaction?

    PubMed Central

    Maghuly, Fatemeh; Ramkat, Rose C.; Laimer, Margit

    2014-01-01

    Considering the importance of microRNAs (miRNAs) in the regulation of essential processes in plant pathogen interactions, it is not surprising that, while plant miRNA sequences counteract viral attack via antiviral RNA silencing, viruses in turn have developed antihost defense mechanisms blocking these RNA silencing pathways and establish a counter-defense. In the current study, computational and stem-loop Reverse Transcription – Polymerase Chain Reaction (RT-PCR) approaches were employed to a) predict and validate virus encoded mature miRNAs (miRs) in 39 DNA-A sequences of the bipartite genomes of African cassava mosaic virus (ACMV) and East African cassava mosaic virus-Uganda (EACMV-UG) isolates, b) determine whether virus encoded miRs/miRs* generated from the 5′/3′ harpin arms have the capacity to bind to genomic sequences of the host plants Jatropha or cassava and c) investigate whether plant encoded miR/miR* sequences have the potential to bind to the viral genomes. Different viral pre-miRNA hairpin sequences and viral miR/miR* length variants occurring as isomiRs were predicted in both viruses. These miRNAs were located in three Open Reading Frames (ORFs) and in the Intergenic Region (IR). Moreover, various target genes for miRNAs from both viruses were predicted and annotated in the host plant genomes indicating that they are involved in biotic response, metabolic pathways and transcription factors. Plant miRs/miRs* from conserved and highly expressed families were identified, which were shown to have potential targets in the genome of both begomoviruses, representing potential plant miRNAs mediating antiviral defense. This is the first assessment of predicted viral miRs/miRs* of ACMV and EACMV-UG and host plant miRNAs, providing a reference point for miRNA identification in pathogens and their hosts. These findings will improve the understanding of host- pathogen interaction pathways and the function of viral miRNAs in Euphorbiaceous crop plants. PMID

  19. Contrasting host-pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes.

    PubMed

    Desjardins, Christopher A; Sanscrainte, Neil D; Goldberg, Jonathan M; Heiman, David; Young, Sarah; Zeng, Qiandong; Madhani, Hiten D; Becnel, James J; Cuomo, Christina A

    2015-01-01

    Obligate intracellular pathogens depend on their host for growth yet must also evade detection by host defenses. Here we investigate host adaptation in two Microsporidia, the specialist Edhazardia aedis and the generalist Vavraia culicis, pathogens of disease vector mosquitoes. Genomic analysis and deep RNA-Seq across infection time courses reveal fundamental differences between these pathogens. E. aedis retains enhanced cell surface modification and signalling capacity, upregulating protein trafficking and secretion dynamically during infection. V. culicis is less dependent on its host for basic metabolites and retains a subset of spliceosomal components, with a transcriptome broadly focused on growth and replication. Transcriptional profiling of mosquito immune responses reveals that response to infection by E. aedis differs dramatically depending on the mode of infection, and that antimicrobial defensins may play a general role in mosquito defense against Microsporidia. This analysis illuminates fundamentally different evolutionary paths and host interplay of specialist and generalist pathogens. PMID:25968466

  20. Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses

    PubMed Central

    Korth, Marcus J.; Tchitchek, Nicolas; Benecke, Arndt; Katze, Michael G.

    2012-01-01

    Influenza virus research has recently undergone a shift from a virus-centric perspective to one that embraces the full spectrum of virus-host interactions and cellular signaling events that determine disease outcome. This change has been brought about by the increasing use and expanding scope of high-throughput molecular profiling and computational biology, which together fuel discovery in systems biology. In this review, we show how these approaches have revealed an uncontrolled inflammatory response as a contributor to the extreme virulence of the 1918 pandemic and avian H5N1 viruses, and how this response differs from that induced by the 2009 H1N1 viruses responsible for the most recent influenza pandemic. We also discuss how new animal models, such as the Collaborative Cross mouse systems genetics platform, are key to the necessary systematic investigation of the impact of host genetics on infection outcome, how genome-wide RNAi screens have identified hundreds of cellular factors involved in viral replication, and how systems biology approaches are making possible the rational design of new drugs and vaccines against an ever-evolving respiratory virus. PMID:23218769

  1. Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

    PubMed

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Inoue, Makoto; Tonthat, Nam K; Bain, Judith M; Louw, Johanna; Shinohara, Mari L; Erwig, Lars P; Schumacher, Maria A; Ko, Dennis C; Heitman, Joseph

    2015-09-01

    Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-locked phenotype indicating that calcineurin governs the dimorphic transition. Genetic analysis in this study reveals that two calcineurin A catalytic subunits (out of three) are functionally diverged. Homology modeling illustrates modes of resistance resulting from amino substitutions in the interface between each calcineurin subunit and the inhibitory drugs. In addition, we show how the dimorphic transition orchestrated by calcineurin programs different outcomes during host-pathogen interactions. For example, when macrophages phagocytose Mucor yeast, subsequent phagosomal maturation occurs, indicating host cells respond appropriately to control the pathogen. On the other hand, upon phagocytosis of spores, macrophages fail to form mature phagosomes. Cytokine production from immune cells differs following exposure to yeast versus spores (which germinate into hyphae). Thus, the morphogenic transition can be targeted as an efficient treatment option against Mucor infection. In addition, genetic analysis (including gene disruption and mutational studies) further strengthens the understanding of calcineurin and provides a foundation to develop antifungal agents targeting calcineurin to deploy against Mucor and other pathogenic fungi. PMID:26010100

  2. Quantitative Genetic Interactions Reveal Layers of Biological Modularity

    PubMed Central

    Beltrao, Pedro; Cagney, Gerard; Krogan, Nevan J.

    2010-01-01

    In the past, biomedical research has embraced a reductionist approach, primarily focused on characterizing the individual components that comprise a system of interest. Recent technical developments have significantly increased the size and scope of data describing biological systems. At the same time, advances in the field of systems biology have evoked a broader view of how the underlying components are interconnected. In this essay, we discuss how quantitative genetic interaction mapping has enhanced our view of biological systems, allowing a deeper functional interrogation at different biological scales. PMID:20510918

  3. Proteomics analysis of EV71-infected cells reveals the involvement of host protein NEDD4L in EV71 replication.

    PubMed

    Kuo, Rei-Lin; Lin, Ya-Han; Wang, Robert Yung-Liang; Hsu, Chia-Wei; Chiu, Yi-Ting; Huang, Hsing-I; Kao, Li-Ting; Yu, Jau-Song; Shih, Shin-Ru; Wu, Chih-Ching

    2015-04-01

    Enterovirus 71 (EV71) is a human enterovirus that has seriously affected the Asia-Pacific area for the past two decades. EV71 infection can result in mild hand-foot-and-mouth disease and herpangina and may occasionally lead to severe neurological complications in children. However, the specific biological processes that become altered during EV71 infection remain unclear. To further explore host responses upon EV71 infection, we identified proteins differentially expressed in EV71-infected human glioblastoma SF268 cells using isobaric mass tag (iTRAQ) labeling coupled with multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Network analysis of proteins altered in cells infected with EV71 revealed that the changed biological processes are related to protein and ion transport, regulation of protein degradation, and homeostatic processes. We confirmed that the levels of NEDD4L and PSMF1 were increased and reduced, respectively, in EV71-infected cells compared to mock-infected control cells. To determine the physiological relevance of our findings, we investigated the consequences of EV71 infection in cells with NEDD4L or PSMF1 depletion. We found that the depletion of NEDD4L significantly reduced the replication of EV71, whereas PSMF1 knockdown enhanced EV71 replication. Collectively, our findings provide the first evidence of proteome-wide dysregulation by EV71 infection and suggest a novel role for the host protein NEDD4L in the replication of this virus. PMID:25785312