Sample records for article pathogen pathway

  1. FY2003 LDRD Final Annual Report Article: Pathogen Pathway Project

    SciTech Connect

    Fitch, J P; McCutchen-Maloney, S L

    2003-11-10

    Understanding virulence mechanisms of bacterial pathogens is vital to anticipating biological threats and to improving detectors, vaccines, and treatments. This project will characterize factors responsible for virulence of Yersinia pestis, the causative agent of plague and a biothreat agent, which has an inducible Type III secretion virulence mechanism also found in other animal, plant, and human pathogens. Our approach relies on genomic and proteomic characterization of Y. pestis in addition to a bioinformatic infrastructure. Scientific and technical capabilities developed in this project can be applied to other microbes of interest. This work will establish a significant new direction for biodefense at LLNL and expand our national and international scientific collaborations.

  2. Review article Melatonin synthesis pathway

    E-print Network

    Boyer, Edmond

    Review article Melatonin synthesis pathway: circadian regulation of the genes encoding the key three enzymes of the melatonin synthesis pathway (tryptophan hydroxylase (TPH), arylalkylamine) their tissue-specific expression in the pineal gland and the retina. © Inra/ Elsevier, Paris melatonin

  3. Innate immunity in Drosophila: Pathogens and pathways.

    PubMed

    Govind, Shubha

    2008-02-01

    Following in the footsteps of traditional developmental genetics, research over the last 15 years has shown that innate immunity against bacteria and fungi is governed largely by two NF-kappaB signal transduction pathways, Toll and IMD. Antiviral immunity appears to stem from RNA interference, whereas resistance against parasitoids is conferred by Toll signaling. The identification of these post-transcriptional regulatory mechanisms and the annotation of most Drosophila immunity genes have derived from functional genomic studies using "model" pathogens, intact animals and cell lines. The D. melanogaster host has thus provided the core information that can be used to study responses to natural microbial and metazoan pathogens as they become identified, as well as to test ideas of selection and evolutionary change. These analyses are of general importance to understanding mechanisms of other insect host-pathogen interactions and determinants of variation in host resistance. PMID:20485470

  4. Review article Avian pathogenic Escherichia coli (APEC)

    E-print Network

    Paris-Sud XI, Université de

    Review article Avian pathogenic Escherichia coli (APEC) Maryvonne Dho-Moulina John Morris Inra/Elscvier, Paris. avian / Escherichia coli / virulence / fimbriae / capsule / aerobactin.int-a. li- #12;Résumé-Escherichia coli pathogènes aviaires (APEC). Les Escherichia coli pathogènes aviaires

  5. ORIGINAL ARTICLE Multiple introductions of highly pathogenic avian

    E-print Network

    Cai, Long

    ORIGINAL ARTICLE Multiple introductions of highly pathogenic avian influenza H5N1 viruses Highly pathogenic H5N1 and low pathogenic H9N2 influenza viruses are endemic to poultry markets markets, whereas highly pathogenic H5N1 viruses occurred sporadically, with peaks of activity in cooler

  6. Original article Enteric bacterial pathogen detection in southern sea otters

    E-print Network

    Paris-Sud XI, Université de

    Original article Enteric bacterial pathogen detection in southern sea otters (Enhydra lutris nereis and dead sea otters from California for specific enteric bacterial pathogens (Campylobacter, Salmonella associations between detection of these pathogens in otter feces and demographic or environmental risk factors

  7. Intervention of Phytohormone Pathways by Pathogen Effectors[OPEN

    PubMed Central

    Kazan, Kemal; Lyons, Rebecca

    2014-01-01

    The constant struggle between plants and microbes has driven the evolution of multiple defense strategies in the host as well as offense strategies in the pathogen. To defend themselves from pathogen attack, plants often rely on elaborate signaling networks regulated by phytohormones. In turn, pathogens have adopted innovative strategies to manipulate phytohormone-regulated defenses. Tactics frequently employed by plant pathogens involve hijacking, evading, or disrupting hormone signaling pathways and/or crosstalk. As reviewed here, this is achieved mechanistically via pathogen-derived molecules known as effectors, which target phytohormone receptors, transcriptional activators and repressors, and other components of phytohormone signaling in the host plant. Herbivores and sap-sucking insects employ obligate pathogens such as viruses, phytoplasma, or symbiotic bacteria to intervene with phytohormone-regulated defenses. Overall, an improved understanding of phytohormone intervention strategies employed by pests and pathogens during their interactions with plants will ultimately lead to the development of new crop protection strategies. PMID:24920334

  8. Review article Pathogenic diversity of Escherichia coli

    E-print Network

    Boyer, Edmond

    and systemic infections in humans and other animals. The spectrum of diseases caused by E. coli is due termed pathogenicity islands (PAls) that are absent from the genomes of commen- sal E. coli strains. PAls are likely to have been transferred horizontally and may have integrated into the E. coli chromosome through

  9. Review article Pathogenic role of gastric Helicobacter sp

    E-print Network

    Paris-Sud XI, Université de

    Review article Pathogenic role of gastric Helicobacter sp in domestic carnivores P Lecoindre M more about helicobacteria in domestic carnivores, their morphologic characteristics, their taxonomia pathogène de Helicobacter sp gastrique chez les carnivores domestiques. Grâce u des études phylo

  10. The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

    PubMed Central

    Dalluge, Joseph J.; Welchlin, Cole W.; Hughes, John; Han, Wei; Blackwell, Timothy S.; Laguna, Theresa A.; Williams, Bryan J.

    2014-01-01

    The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards ?2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-? production, likely through NF-?B activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic. PMID:25350753

  11. Original article Signaling pathways involved in liver injury

    E-print Network

    Paris-Sud XI, Université de

    Original article Signaling pathways involved in liver injury and regeneration in rabbit hemorrhagic and STAT pathways during RHD-induced liver injury. Rabbits were infected with 2 · 104 hemagglutination. The current findings suggest that activation of JNK is an essential component in liver injury mediated

  12. Skin Commensals Amplify the Innate Immune Response to Pathogens by Activation of Distinct Signaling Pathways

    Microsoft Academic Search

    Ines Wanke; Heiko Steffen; Christina Christ; Bernhard Krismer; Friedrich Götz; Andreas Peschel; Martin Schaller; Birgit Schittek

    2011-01-01

    Little is known about the impact of different microbial signals on skin barrier organ function and the interdependency between resident microflora and pathogenic microorganisms. This study shows that commensal and pathogenic staphylococci differ in their ability to induce expression of antimicrobial peptides\\/proteins (AMPs) and activate different signaling pathways in human primary keratinocytes. Whereas secreted factors of skin commensals induce expression

  13. Bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus Aspergillus fumigatus.

    PubMed

    König, Claudia C; Scherlach, Kirstin; Schroeckh, Volker; Horn, Fabian; Nietzsche, Sandor; Brakhage, Axel A; Hertweck, Christian

    2013-05-27

    Stimulating encounter: The intimate, physical interaction between the soil-derived bacterium Streptomyces rapamycinicus and the human pathogenic fungus Aspergillus fumigatus led to the activation of an otherwise silent polyketide synthase (PKS) gene cluster coding for an unusual prenylated polyphenol (fumicycline A). The meroterpenoid pathway is regulated by a pathway-specific activator gene as well as by epigenetic factors. PMID:23649940

  14. RESEARCH ARTICLE Open Access Pathogen-induced Caenorhabditis elegans

    E-print Network

    Paris-Sud XI, Université de

    of development of Caenorhabditis elegans larvae fed with different bacterial strains on stress resistance to nematodes. Exposure to the pathogen during development did not affect larval survival. However, the development of nematodes on the pathogenic bacterial strains increased lifespan of adult nematodes exposed

  15. Polyprenyl-dependent glycan assembly pathways in microbial pathogens

    E-print Network

    Hartley, Meredith Diane

    2011-01-01

    Polyisoprenyl-dependent glycan assembly pathways form the basis for the biosynthesis of many complex glycoconjugates. This thesis addresses key aspects of undecaprenyl-phosphate related processes; undecaprenol is the linear ...

  16. The Danger Signal S100B Integrates Pathogen– and Danger–Sensing Pathways to Restrain Inflammation

    PubMed Central

    Riuzzi, Francesca; Bonifazi, Pierluigi; Zelante, Teresa; Zagarella, Silvia; Bistoni, Francesco; Donato, Rosario; Romani, Luigina

    2011-01-01

    Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen– and danger–sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen–induced inflammation and a pathogen–sensing mechanism resolves danger–induced inflammation. PMID:21423669

  17. Review article Escherichia coli as a pathogen in dogs and cats

    E-print Network

    Paris-Sud XI, Université de

    Review article Escherichia coli as a pathogen in dogs and cats Lothar Beutin Robert Koch; accepted 17December 1998) Abstraet-Certain strains of Escherichia coli behave as pathogens in dogs and cats were clearly associated with enteric disease in young dogs. ETEC isolates from diar- rhoeic dogs were

  18. ORIGINAL ARTICLE Moths that Vector a Plant Pathogen also Transport

    E-print Network

    Arnold, A. Elizabeth

    in the southeastern USA and used data from the nuclear internal transcribed spacer (ITS rDNA) to compare communities sequences of mycoparasitic Fusarium heterosporum and to three distinct endophytic fungi isolated from a plant pathogen, to transmit other guilds of fungi. In turn, the potential for insects to transmit plant

  19. Immune signaling pathways activated in response to different pathogenic micro-organisms in Bombyx mori.

    PubMed

    Liu, Wei; Liu, Jiabin; Lu, Yahong; Gong, Yongchang; Zhu, Min; Chen, Fei; Liang, Zi; Zhu, Liyuan; Kuang, Sulan; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

    2015-06-01

    The JAK/STAT, Toll, Imd, and RNAi pathways are the major signaling pathways associated with insect innate immunity. To explore the different immune signaling pathways triggered in response to pathogenic micro-organism infections in the silkworm, Bombyx mori, the expression levels of the signal transducer and activator of transcription (BmSTAT), spatzle-1 (Bmspz-1), peptidoglycan-recognition protein LB (BmPGRP-LB), peptidoglycan-recognition protein LE (BmPGRP-LE), argonaute 2 (Bmago2), and dicer-2 (Bmdcr2) genes after challenge with Escherichia coli (E. coli), Serratiamarcescens (Sm), Bacillus bombyseptieus (Bab), Beauveriabassiana (Beb), nucleopolyhedrovirus (BmNPV), cypovirus (BmCPV), bidensovirus (BmBDV), or Nosemabombycis (Nb) were determined using real-time PCR. We found that the JAK/STAT pathway could be activated by challenge with BmNPV and BmBDV, the Toll pathway could be most robustly induced by challenge with Beb, the Imd pathway was mainly activated in response to infection by E. coli and Sm, and the RNAi pathway was not activated by viral infection, but could be triggered by some bacterial infections. These findings yield insights into the immune signaling pathways activated in response to different pathogenic micro-organisms in the silkworm. PMID:25745806

  20. Degradation of aromatic compounds through the ?-ketoadipate pathway is required for pathogenicity of the tomato wilt pathogen Fusarium oxysporum f. sp. lycopersici.

    PubMed

    Michielse, Caroline B; Reijnen, Linda; Olivain, Chantal; Alabouvette, Claude; Rep, Martijn

    2012-12-01

    Plant roots react to pathogen attack by the activation of general and systemic resistance, including the lignification of cell walls and increased release of phenolic compounds in root exudate. Some fungi have the capacity to degrade lignin using ligninolytic extracellular peroxidases and laccases. Aromatic lignin breakdown products are further catabolized via the ?-ketoadipate pathway. In this study, we investigated the role of 3-carboxy-cis,cis-muconate lactonizing enzyme (CMLE), an enzyme of the ?-ketoadipate pathway, in the pathogenicity of Fusarium oxysporum f. sp. lycopersici towards its host, tomato. As expected, the cmle deletion mutant cannot catabolize phenolic compounds known to be degraded via the ?-ketoadipate pathway. In addition, the mutant is impaired in root invasion and is nonpathogenic, even though it shows normal superficial root colonization. We hypothesize that the ?-ketoadipate pathway in plant-pathogenic, soil-borne fungi is necessary to degrade phenolic compounds in root exudate and/or inside roots in order to establish disease. PMID:22827542

  1. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells

    Microsoft Academic Search

    Estelle Bettelli; Yijun Carrier; Wenda Gao; Thomas Korn; Terry B. Strom; Mohamed Oukka; Howard L. Weiner; Vijay K. Kuchroo

    2006-01-01

    On activation, T cells undergo distinct developmental pathways, attaining specialized properties and effector functions. T-helper (TH) cells are traditionally thought to differentiate into TH1 and TH2 cell subsets. TH1 cells are necessary to clear intracellular pathogens and TH2 cells are important for clearing extracellular organisms. Recently, a subset of interleukin (IL)-17-producing T (TH17) cells distinct from TH1 or TH2 cells

  2. The STING pathway and regulation of innate immune signaling in response to DNA pathogens

    Microsoft Academic Search

    Hiroki Ishikawa; Glen N. Barber

    2011-01-01

    The innate immune system has evolved a variety of sensing mechanisms to detect and counter microbial invasion. These include\\u000a the Toll-like receptor (TLR), cytoplasmic, nucleotide binding oligomerization domain (NOD)-like receptor and RIG-I-like helicase\\u000a (RLH) pathways. However, how the cell detects pathogen-associated DNA to trigger host defense, including the production of\\u000a interferon, remains to be fully clarified. Understanding these processes could

  3. The Renaissance of Bacillosamine and Its Derivatives: Pathway Characterization and Implications in Pathogenicity

    PubMed Central

    2015-01-01

    Prokaryote-specific sugars, including N,N?-diacetylbacillosamine (diNAcBac) and pseudaminic acid, have experienced a renaissance in the past decade because of their discovery in glycans related to microbial pathogenicity. DiNAcBac is found at the reducing end of oligosaccharides of N- and O-linked bacterial protein glycosylation pathways of Gram-negative pathogens, including Campylobacter jejuni and Neisseria gonorrhoeae. Further derivatization of diNAcBac results in the nonulosonic acid known as legionaminic acid, which was first characterized in the O-antigen of the lipopolysaccharide (LPS) in Legionella pneumophila. Pseudaminic acid, an isomer of legionaminic acid, is also important in pathogenic bacteria such as Helicobacter pylori because of its occurrence in O-linked glycosylation of flagellin proteins, which plays an important role in flagellar assembly and motility. Here, we present recent advances in the characterization of the biosynthetic pathways leading to these highly modified sugars and investigation of the roles that each plays in bacterial fitness and pathogenicity. PMID:24383882

  4. Population History and Pathways of Spread of the Plant Pathogen Phytophthora plurivora

    PubMed Central

    Schoebel, Corine N.; Stewart, Jane; Gruenwald, Niklaus J.; Rigling, Daniel; Prospero, Simone

    2014-01-01

    Human activity has been shown to considerably affect the spread of dangerous pests and pathogens worldwide. Therefore, strict regulations of international trade exist for particularly harmful pathogenic organisms. Phytophthora plurivora, which is not subject to regulations, is a plant pathogen frequently found on a broad range of host species, both in natural and artificial environments. It is supposed to be native to Europe while resident populations are also present in the US. We characterized a hierarchical sample of isolates from Europe and the US and conducted coalescent-, migration, and population genetic analysis of sequence and microsatellite data, to determine the pathways of spread and the demographic history of this pathogen. We found P. plurivora populations to be moderately diverse but not geographically structured. High levels of gene flow were observed within Europe and unidirectional from Europe to the US. Coalescent analyses revealed a signal of a recent expansion of the global P. plurivora population. Our study shows that P. plurivora has most likely been spread around the world by nursery trade of diseased plant material. In particular, P. plurivora was introduced into the US from Europe. International trade has allowed the pathogen to colonize new environments and/or hosts, resulting in population growth. PMID:24427303

  5. PTS1 peroxisomal import pathway plays shared and distinct roles to PTS2 pathway in development and pathogenicity of Magnaporthe oryzae.

    PubMed

    Wang, Jiaoyu; Zhang, Zhen; Wang, Yanli; Li, Ling; Chai, Rongyao; Mao, Xueqin; Jiang, Hua; Qiu, Haiping; Du, Xinfa; Lin, Fucheng; Sun, Guochang

    2013-01-01

    Peroxisomes participate in various important metabolisms and are required in pathogenicity of fungal plant pathogens. Peroxisomal matrix proteins are imported from cytoplasm into peroxisomes through peroxisomal targeting signal 1 (PTS1) or peroxisomal targeting signal 2 (PTS2) import pathway. PEX5 and PEX7 genes participate in the two pathways respectively. The involvement of PEX7 mediated PTS2 import pathway in fungal pathogenicity has been documented, while that of PTS1 remains unclear. Through null mutant analysis of MoPEX5, the PEX5 homolog in Magnaporthe oryzae, we report the crucial roles of PTS1 pathway in the development and host infection in the rice blast fungus, and compared with those of PTS2. We found that MoPEX5 disruption specifically blocked the PTS1 pathway. ?mopex5 was unable to use lipids as sole carbon source and lost pathogenicity completely. Similar as ?mopex7, ?mopex5 exhibited significant reduction in lipid utilization and mobilization, appressorial turgor genesis and H(2)O(2) resistance. Additionally, ?mopex5 presented some distinct defects which were undetected in ?mopex7 in vegetative growth, conidial morphogenesis, appressorial morphogenesis and melanization. The results indicated that the PTS1 peroxisomal import pathway, in addition to PTS2, is required for fungal development and pathogenicity of the rice blast fungus, and also, as a main peroxisomal import pathway, played a more predominant role than PTS2. PMID:23405169

  6. A sophisticated network of signaling pathways regulates stomatal defenses to bacterial pathogens.

    PubMed

    Arnaud, Dominique; Hwang, Ildoo

    2014-11-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. A decade ago, stomata have been shown to play an important role in plant defense as a part of the innate immune response. Indeed, plants actively close their stomata upon contact with microbes thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we will present current knowledges of molecular mechanisms and signaling pathways implicated in stomatal defenses with a particular attention on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns (PAMPs) and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species (ROS), nitric oxide (NO) and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays with components regulating hormonal signaling pathways. We will also discuss on strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine. PMID:25366179

  7. Comprehensive database of Chorismate synthase enzyme from shikimate pathway in pathogenic bacteria

    PubMed Central

    2013-01-01

    Background Infectious diseases are major public health problem. It is increasingly affecting more than 50 million people worldwide. Targeting shikimate pathway could be efficiently used for the development of broad spectrum antimicrobial compound against variety of infectious diseases. Chorismate synthase is an enzyme in shikimate pathway that catalyzes Phosphoenol pyruvate to chorismate in most of the prokaryotic bacteria. This step is crucial for its growth, since Chorismate acts as a precursor molecule for the synthesis of aromatic amino acids. Hence, we present a comprehensive database of Chorismate Synthase Database (CSDB) which is a manually curated database. It provides information on the sequence, structure and biological activity of chorismate synthase from shikimate pathway of pathogenic bacteria. Design of suitable inhibitors for this enzyme, hence could be a probable solution to destroy its proteomic machinery and thereby inhibit the bacterial growth. Description The aim of this study was to characterise chorismate synthase enzyme belonging to pathogenic bacteria to analysis the functional and structural characterization of chorismate synthase is very important for both structure-based and ligand based drug design. Conclusions The broad range of data easy to use user interface makes csdb.in a useful database for researchers in designing drugs. PMID:23697663

  8. The Pathogenic Role of the Canonical Wnt Pathway in Age-Related Macular Degeneration

    PubMed Central

    Zhou, Ti; Hu, Yang; Chen, Ying; Zhou, Kevin K.; Zhang, Bin; Gao, Guoquan; Ma, Jian-xing

    2010-01-01

    Purpose. The authors' previous studies showed that the Wnt signaling pathway is activated in the retinas and retinal pigment epithelia of animal models of age-related macular degeneration (AMD) and diabetic retinopathy (DR). The purpose of this study was to investigate the role of the canonical Wnt pathway in pathogenesis of these diseases. Methods. The Wnt pathway was activated using the Wnt3a-conditioned medium and adenovirus expressing a constitutively active mutant of ?-catenin (Ad-S37A) in ARPE19, a cell line derived from human RPE. Ad-S37A was injected into the vitreous of normal rats to activate the Wnt pathway in the retina. Accumulation of ?-catenin was determined by Western blot analysis, and its nuclear translocation was revealed by immunocytochemistry. Inflammatory factors were quantified by Western blot analysis and ELISA. Oxidative stress was determined by measuring intracellular reactive oxygen species (ROS) generation and nitrotyrosine levels. Results. The Wnt3a-conditioned medium and Ad-S37A both increased ?-catenin levels and its nuclear translocation in ARPE19 cells, suggesting activation of the canonical Wnt pathway. Activation of the Wnt pathway significantly upregulated the expression of VEGF, NF-?B, and TNF-?. Further, Ad-S37A induced ROS generation in a dose-dependent manner. Wnt3a also induced a twofold increase of ROS generation. Intravitreal injection of Ad-S37A upregulated the expression of VEGF, ICAM-1, NF-?B, and TNF-? and increased protein nitrotyrosine levels in the retinas of normal rats. Conclusions. Activation of the canonical Wnt pathway is sufficient to induce retinal inflammation and oxidative stress and plays a pathogenic role in AMD and DR. PMID:19875668

  9. Dothistroma pini, a Forest Pathogen, Contains Homologs of Aflatoxin Biosynthetic Pathway Genes

    PubMed Central

    Bradshaw, Rosie E.; Bhatnagar, Deepak; Ganley, Rebecca J.; Gillman, Carmel J.; Monahan, Brendon J.; Seconi, Janet M.

    2002-01-01

    Homologs of aflatoxin biosynthetic genes have been identified in the pine needle pathogen Dothistroma pini. D. pini produces dothistromin, a difuranoanthraquinone toxin with structural similarity to the aflatoxin precursor versicolorin B. Previous studies with purified dothistromin suggest a possible role for this toxin in pathogenicity. By using an aflatoxin gene as a hybridization probe, a genomic D. pini clone was identified that contained four dot genes with similarity to genes in aflatoxin and sterigmatocystin gene clusters with predicted activities of a ketoreductase (dotA), oxidase (dotB), major facilitator superfamily transporter (dotC), and thioesterase (dotD). A D. pini dotA mutant was made by targeted gene replacement and shown to be severely impaired in dothistromin production, confirming that dotA is involved in dothistromin biosynthesis. Accumulation of versicolorin A (a precursor of aflatoxin) by the dotA mutant confirms that the dotA gene product is involved in an aflatoxin-like biosynthetic pathway. Since toxin genes have been found to be clustered in fungi in every case analyzed so far, it is speculated that the four dot genes may comprise part of a dothistromin biosynthetic gene cluster. A fifth gene, ddhA, is not a homolog of aflatoxin genes and could be at one end of the dothistromin cluster. These genes will allow comparative biochemical and genetic studies of the aflatoxin and dothistromin biosynthetic pathways and may also lead to new ways to control Dothistroma needle blight. PMID:12039746

  10. The twin arginine protein transport pathway exports multiple virulence proteins in the plant pathogen Streptomyces scabies.

    PubMed

    Joshi, Madhumita V; Mann, Stefan G; Antelmann, Haike; Widdick, David A; Fyans, Joanna K; Chandra, Govind; Hutchings, Matthew I; Toth, Ian; Hecker, Michael; Loria, Rosemary; Palmer, Tracy

    2010-07-01

    Summary Streptomyces scabies is one of a group of organisms that causes the economically important disease potato scab. Analysis of the S. scabies genome sequence indicates that it is likely to secrete many proteins via the twin arginine protein transport (Tat) pathway, including several proteins whose coding sequences may have been acquired through horizontal gene transfer and share a common ancestor with proteins in other plant pathogens. Inactivation of the S. scabies Tat pathway resulted in pleiotropic phenotypes including slower growth rate and increased permeability of the cell envelope. Comparison of the extracellular proteome of the wild type and DeltatatC strains identified 73 predicted secretory proteins that were present in reduced amounts in the tatC mutant strain, and 47 Tat substrates were verified using a Tat reporter assay. The DeltatatC strain was almost completely avirulent on Arabidopsis seedlings and was delayed in attaching to the root tip relative to the wild-type strain. Genes encoding 14 candidate Tat substrates were individually inactivated, and seven of these mutants were reduced in virulence compared with the wild-type strain. We conclude that the Tat pathway secretes multiple proteins that are required for full virulence. PMID:20487278

  11. Genomics of iron acquisition in the plant pathogen Erwinia amylovora: insights in the biosynthetic pathway of the siderophore desferrioxamine E.

    PubMed

    Smits, Theo H M; Duffy, Brion

    2011-10-01

    Genomics has clarified the biosynthetic pathway for desferrioxamine E critical for iron acquisition in the enterobacterial fire blight pathogen Erwinia amylovora. Evidence for each of the individual steps and the role of desferrioxamine E biosynthesis in pathogen virulence and cell protection from host defenses is presented. Using comparative genomics, it can be concluded that desferrioxamine biosynthesis is ancestral within the genera Erwinia and Pantoea. PMID:21814817

  12. Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

    Microsoft Academic Search

    D Arnoult; F Petit; J D Lelièvie; D Lecossier; A Hance; V Monceaux; R Ho Tsong Fang; B Huntrel; J C Ameisen; J Estaquier

    2003-01-01

    Studies of human immunodeficiency virus (HIV) and nonhuman primate models of pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections have suggested that enhanced ex vivo CD4 T-cell death is a feature of pathogenic infection in vivo. However, the relative contributions of the extrinsic and intrinsic pathways to programmed T-cell death in SIV infection have not been studied. We report here

  13. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways

    PubMed Central

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR?/? and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR?/? mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1+) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C–C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-?1 (TGF?1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that are consistent with a possible role of AhR in wet AMD. The data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus; GEO Submission No. GSE56983, NCBI Tracking System No. 17021116. PMID:25186463

  14. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.

    PubMed

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR(-/-) and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR(-/-) mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1(+) ) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C-C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-?1 (TGF?1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that are consistent with a possible role of AhR in wet AMD. The data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus; GEO Submission No. GSE56983, NCBI Tracking System No. 17021116. PMID:25186463

  15. Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes

    PubMed Central

    Chen, Li-Hong; Köseo?lu, Volkan K.; Güvener, Zehra T.; Myers-Morales, Tanya; Reed, Joseph M.; D'Orazio, Sarah E. F.; Miller, Kurt W.; Gomelsky, Mark

    2014-01-01

    We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (?pdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence. PMID:25101646

  16. The Drosophila melanogaster Toll Pathway Participates in Resistance to Infection by the Gram-Negative Human Pathogen Pseudomonas aeruginosa

    Microsoft Academic Search

    Gee W. Lau; Boyan C. Goumnerov; Cynthia L. Walendziewicz; Jennifer Hewitson; Wenzhong Xiao; Shalina Mahajan-Miklos; Ronald G. Tompkins; Lizabeth A. Perkins; Laurence G. Rahme

    2003-01-01

    Pseudomonas aeruginosa is a gram-negative pathogen that infects immunocompromised and cystic fibrosis patients. The molecular basis of the host-P. aeruginosa interaction and the effect of specific P. aeruginosa virulence factors on various components of the innate immunity pathways are largely unknown. We examine interactions between P. aeruginosa virulence factors and components of innate immunity response in the Drosophila melanogaster model

  17. RESEARCH ARTICLE Open Access Activation of pro-oncogenic pathways in

    E-print Network

    Paris-Sud XI, Université de

    RESEARCH ARTICLE Open Access Activation of pro-oncogenic pathways in colorectal hyperplastic polyps involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK a malignant potential. Keywords: Hyperplastic polyps, Colorectal, Progastrin, ERK, STAT3, Pro-oncogenic

  18. Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans

    PubMed Central

    Lee, I. Russel; Yang, Liting; Sebetso, Gaseene; Allen, Rebecca; Doan, Thi H. N.; Blundell, Ross; Lui, Edmund Y. L.; Morrow, Carl A.; Fraser, James A.

    2013-01-01

    Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In contrast, uric acid is completely degraded to ammonia in most fungi. Currently, relatively little is known about uric acid catabolism in the fungal pathogen Cryptococcus neoformans even though this yeast is commonly isolated from uric acid-rich pigeon guano. In addition, uric acid utilization enhances the production of the cryptococcal virulence factors capsule and urease, and may potentially modulate the host immune response during infection. Based on these important observations, we employed both Agrobacterium-mediated insertional mutagenesis and bioinformatics to predict all the uric acid catabolic enzyme-encoding genes in the H99 genome. The candidate C. neoformans uric acid catabolic genes identified were named: URO1 (urate oxidase), URO2 (HIU hydrolase), URO3 (OHCU decarboxylase), DAL1 (allantoinase), DAL2,3,3 (allantoicase-ureidoglycolate hydrolase fusion protein), and URE1 (urease). All six ORFs were then deleted via homologous recombination; assaying of the deletion mutants' ability to assimilate uric acid and its pathway intermediates as the sole nitrogen source validated their enzymatic functions. While Uro1, Uro2, Uro3, Dal1 and Dal2,3,3 were demonstrated to be dispensable for virulence, the significance of using a modified animal model system of cryptococcosis for improved mimicking of human pathogenicity is discussed. PMID:23667704

  19. Delineation of Upstream Signaling Events in the Salmonella Pathogenicity Island 2 Transcriptional Activation Pathway

    PubMed Central

    Kim, Charles C.; Falkow, Stanley

    2004-01-01

    Survival and replication in the intracellular environment are critical components of the ability of Salmonella enterica serovar Typhimurium to establish systemic infection in the murine host. Intracellular survival is mediated by a number of genetic loci, including Salmonella pathogenicity island 2 (SPI2). SPI2 is a 40-kb locus encoding a type III secretion system that secretes effector molecules, which permits bacterial survival and replication in the intracellular environment of host cells. A two-component regulatory system, ssrAB, is also encoded in SPI2 and controls expression of the secretion system and effectors. While the environmental signals to which SPI2 responds in vivo are not known, activation of expression is dependent on OmpR and can be stimulated in vitro by chelation of cations or by a shift from rich to acidic minimal medium. In this work, we demonstrated that SPI2 activation is associated with OmpR in the phosphorylated form (OmpR-P). Mutations in envZ and ackA-pta, which disrupted two distinct sources of OmpR phosphorylation, indicated that SPI2 activation by chelators or a shift from rich to acidic minimal medium is largely dependent on functional EnvZ. In contrast, the PhoPQ pathway is not required for SPI2 activation in the presence of OmpR-P. As in the case of in vitro stimulation, SPI2 expression in macrophages correlates with the presence of OmpR-P. Additionally, EnvZ, but not acetyl phosphate, is required for maximal expression of SPI2 in the intracellular environment, suggesting that the in vitro SPI2 activation pathway is the same as that used in vivo. PMID:15231802

  20. Differential involvement of indole-3-acetic acid biosynthetic pathways in pathogenicity and epiphytic fitness of Erwinia herbicola pv. gypsophilae.

    PubMed

    Manulis, S; Haviv-Chesner, A; Brandl, M T; Lindow, S E; Barash, I

    1998-07-01

    Erwinia herbicola pv. gypsophilae (Ehg), which induces galls on Gypsophila paniculata, harbors two major pathways for indole-3-acetic acid (IAA) synthesis, the indole-3-acetamide (IAM) and indole-3-pyruvate (IPyA) routes, as well as cytokinin biosynthetic genes. Mutants were generated in which the various biosynthetic routes were disrupted separately or jointly in order to assess the contribution of IAA of various origins and cytokinins to pathogenicity and epiphytic fitness. Inactivation of the IAM pathway or cytokinin biosynthesis caused the largest reduction in gall size. Inactivation of the IPyA pathway caused a minor, nonsignificant decrease in pathogenicity. No further reduction in gall size was observed by the simultaneous inactivation of both IAA pathways only or in combination with that of cytokinin production. However, inactivation of the IPyA pathway caused a 14-fold reduction in the population of Ehg on bean plants. Inactivation of the IAM pathway or cytokinin production did not affect epiphytic fitness. While the apparent transcriptional activity of iaaM-inaZ fusion increased slightly in cells of Ehg on bean and gypsophila leaves, compared with that in culture, very high levels of induction were observed in cells injected into gypsophila stems. In contrast, moderate levels of induction of ipdC-inaZ in Ehg were observed on leaves of these plants and in gypsophila stems, when compared with that in culture. These results suggest that the IAM pathway is involved primarily in gall formation and support the main contribution of the IpyA pathway to the epiphytic fitness of this bacterial species. PMID:9650296

  1. Two Functional Type VI Secretion Systems in Avian Pathogenic Escherichia coli Are Involved in Different Pathogenic Pathways

    PubMed Central

    Ma, Jiale; Bao, Yinli; Sun, Min; Dong, Wenyang; Pan, Zihao; Zhang, Wei; Lu, Chengping

    2014-01-01

    Type VI secretion systems (T6SSs) are involved in the pathogenicity of several Gram-negative bacteria. The VgrG protein, a core component and effector of T6SS, has been demonstrated to perform diverse functions. The N-terminal domain of VgrG protein is a homologue of tail fiber protein gp27 of phage T4, which performs a receptor binding function and determines the host specificity. Based on sequence analysis, we found that two putative T6SS loci exist in the genome of the avian pathogenic Escherichia coli (APEC) strain TW-XM. To assess the contribution of these two T6SSs to TW-XM pathogenesis, the crucial clpV clusters of these two T6SS loci and their vgrG genes were deleted to generate a series of mutants. Consequently, T6SS1-associated mutants presented diminished adherence to and invasion of several host cell lines cultured in vitro, decreased pathogenicity in duck and mouse infection models in vivo, and decreased biofilm formation and bacterial competitive advantage. In contrast, T6SS2-associated mutants presented a significant decrease only in the adherence to and invasion of mouse brain microvascular endothelial cell (BMEC) line bEnd.3 and brain tissue of the duck infection model. These results suggested that T6SS1 was involved in the proliferation of APEC in systemic infection, whereas VgrG-T6SS2 was responsible only for cerebral infection. Further study demonstrated that VgrG-T6SS2 was able to bind to the surface of bEnd.3 cells, whereas it did not bind to DF-1 (chicken embryo fibroblast) cells, which further proved the interaction of VgrG-T6SS2 with the surface of BMECs. PMID:24980972

  2. ORIGINAL ARTICLE Cell-to-cell pathway dominates xylem-epidermis hydraulic

    E-print Network

    Holbrook, N. Michele

    ORIGINAL ARTICLE Cell-to-cell pathway dominates xylem-epidermis hydraulic connection the hydraulic linkage between xylem and epidermis, epidermal cell turgor pressure (Pt) in leaves of Tradescantia- tutes a significant part of the leaf hydraulic path from xylem to epidermis. Furthermore, perfusion of H

  3. Toward a molecular pathogenic pathway for Yersinia pestis YopM

    PubMed Central

    Uittenbogaard, Annette M.; Chelvarajan, R. Lakshman; Myers-Morales, Tanya; Gorman, Amanda A.; Brickey, W. June; Ye, Zhan; Kaplan, Alan M.; Cohen, Donald A.; Ting, Jenny P.-Y.; Straley, Susan C.

    2012-01-01

    YopM is one of the six “effector Yops” of the human-pathogenic Yersinia, but its mechanism has not been defined. After delivery to J774A.1 monocyte-like cells, YopM can rapidly bind and activate the serine/threonine kinases RSK1 and PRK2. However, in infected mice, effects of Y. pestis YopM have been seen only after 24–48 h post-infection (p.i.). To identify potential direct effects of YopM in-vivo we tested for effects of YopM at 1 h and 16–18 h p.i. in mice infected systemically with 106 bacteria. At 16 h p.i., there was a robust host response to both parent and ?yopM-1 Y. pestis KIM5. Compared to cells from non-infected mice, CD11b+ cells from spleens of infected mice produced more than 100-fold greater IFN?. In the corresponding sera there were more than 100-fold greater amounts of IFN?, G-CSF, and CXCL9, as well as more than 10-fold greater amounts of IL-6, CXCL10, and CXCL1. The only YopM-related differences were slightly lower CXCL10 and IL-6 in sera from mice infected 16 h with parent compared to ?yopM-1 Y. pestis. Microarray analysis of the CD11b+ cells did not identify consistent transcriptional differences of ?4-fold at 18 h p.i. However, at 1 h p.i. mRNA for early growth response transcription factor 1 (Egr1) was decreased when YopM was present. Bone marrow-derived macrophages infected for 1 h also expressed lower Egr1 message when YopM was present. Infected J774A.1 cells showed greater expression of Egr1 at 1 h p.i. when YopM was present, but this pattern reversed at 3 h. At 6 h p.i., Cxcl10 mRNA was lower in parent-strain infected cells. We conclude that decreased Egr1 expression is a very early transcriptional effect of YopM and speculate that a pathway may exist from RSK1 through Egr1. These studies revealed novel early transcriptional effects of YopM but point to a time after 18 h of infection when critical transitional events lead to later major effects on cytokine gene transcription. PMID:23248776

  4. Metabolic gene clusters encoding the enzymes of two branches of the 3-oxoadipate pathway in the pathogenic yeast Candida albicans.

    PubMed

    Gérecová, Gabriela; Nebohá?ová, Martina; Zeman, Igor; Pryszcz, Leszek P; Tomáška, ?ubomír; Gabaldón, Toni; Nosek, Jozef

    2015-05-01

    The pathogenic yeast Candida albicans utilizes hydroxyderivatives of benzene via the catechol and hydroxyhydroquinone branches of the 3-oxoadipate pathway. The genetic basis and evolutionary origin of this catabolic pathway in yeasts are unknown. In this study, we identified C. albicans genes encoding the enzymes involved in the degradation of hydroxybenzenes. We found that the genes coding for core components of the 3-oxoadipate pathway are arranged into two metabolic gene clusters. Our results demonstrate that C. albicans cells cultivated in media containing hydroxybenzene substrates highly induce the transcription of these genes as well as the corresponding enzymatic activities. We also found that C. albicans cells assimilating hydroxybenzenes cope with the oxidative stress by upregulation of cellular antioxidant systems such as alternative oxidase and catalase. Moreover, we investigated the evolution of the enzymes encoded by these clusters and found that most of them share a particularly sparse phylogenetic distribution among Saccharomycotina, which is likely to have been caused by extensive gene loss. We exploited this fact to find co-evolving proteins that are suitable candidates for the missing enzymes of the pathway. PMID:25743787

  5. Cross-talk between signaling pathways leading to defense against pathogens and insects

    Microsoft Academic Search

    Corné M. J. Pieterse; Annemart Koornneef; H. A. Leon Reyes; T. Ritsema; A. Verhage; R. G. Joosten; M. de Vos; V. R. van Oosten; M. Dicke

    2008-01-01

    In nature, plants interact with a wide range of organisms, some of which\\u000aare harmful (e.g. pathogens, herbivorous insects), while others are beneficial\\u000a(e.g. growth-promoting rhizobacteria, mycorrhizal fungi, and predatory\\u000aenemies of herbivores). During the evolutionary arms race between plants\\u000aand their attackers, primary and secondary immune responses evolved to\\u000arecognize common or highly specialized features of microbial pathogens\\u000a(Chisholm

  6. Detoxification of nitric oxide by flavohemoglobin and the denitrification pathway in the maize pathogen Fusarium verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ephemeral nitric oxide (NO) is a free radical, highly reactive, environmentally rare, and a potent signaling molecule in organisms across kingdoms of life. This gaseous small molecule can freely transverse membranes and has been implicated in aspects of pathogenicity both in animal and plant ho...

  7. Population History and Pathways of Spread of the Plant Pathogen Phytophthora plurivora

    E-print Network

    Grünwald, Niklaus J.

    .pone.0085368 Editor: Mark Gijzen, Agriculture and Agri-Food Canada, Canada Received September 24, 2013 environments. It is supposed to be native to Europe while resident populations are also present in the US. We trade has allowed the pathogen to colonize new environments and/or hosts, resulting in population growth

  8. Silicon induces resistance to the brown spot fungus Cochliobolus miyabeanus by preventing the pathogen from hijacking the rice ethylene pathway.

    PubMed

    Van Bockhaven, Jonas; Spíchal, Lukáš; Novák, Ond?ej; Strnad, Miroslav; Asano, Takayuki; Kikuchi, Shoshi; Höfte, Monica; De Vleesschauwer, David

    2015-04-01

    Although numerous studies have shown the ability of silicon (Si) to mitigate a wide variety of abiotic and biotic stresses, relatively little is known about the underlying mechanism(s). Here, we have investigated the role of hormone defense pathways in Si-induced resistance to the rice brown spot fungus Cochliobolus miyabeanus. To delineate the involvement of multiple hormone pathways, a multidisciplinary approach was pursued, combining exogenous hormone applications, pharmacological inhibitor experiments, time-resolved hormone measurements, and bioassays with hormone-deficient and/or -insensitive mutant lines. Contrary to other types of induced resistance, we found Si-induced brown spot resistance to function independently of the classic immune hormones salicylic acid and jasmonic acid. Our data also rule out a major role of the abscisic acid (ABA) and cytokinin pathways, but suggest that Si mounts resistance to C. miyabeanus by preventing the fungus from hijacking the rice ethylene (ET) machinery. Interestingly, rather than suppressing rice ET signaling per se, Si probably interferes with the production and/or action of fungal ET. Together our findings favor a scenario whereby Si induces brown spot resistance by disarming fungal ET and argue that impairment of pathogen virulence factors is a core resistance mechanism underpinning Si-induced plant immunity. PMID:25625327

  9. The Steroid Catabolic Pathway of the Intracellular Pathogen Rhodococcus equi Is Important for Pathogenesis and a Target for Vaccine Development

    PubMed Central

    van der Geize, R.; Grommen, A. W. F.; Hessels, G. I.; Jacobs, A. A. C.; Dijkhuizen, L.

    2011-01-01

    Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and immunocompromised animals and humans. Despite its importance, there is currently no effective vaccine against the disease. The actinobacteria R. equi and the human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary diseases. Recently, we have shown that essential steps in the cholesterol catabolic pathway are involved in the pathogenicity of M. tuberculosis. Bioinformatic analysis revealed the presence of a similar cholesterol catabolic gene cluster in R. equi. Orthologs of predicted M. tuberculosis virulence genes located within this cluster, i.e. ipdA (rv3551), ipdB (rv3552), fadA6 and fadE30, were identified in R. equi RE1 and inactivated. The ipdA and ipdB genes of R. equi RE1 appear to constitute the ?-subunit and ?-subunit, respectively, of a heterodimeric coenzyme A transferase. Mutant strains RE1?ipdAB and RE1?fadE30, but not RE1?fadA6, were impaired in growth on the steroid catabolic pathway intermediates 4-androstene-3,17-dione (AD) and 3a?-H-4?(3?-propionic acid)-5?-hydroxy-7a?-methylhexahydro-1-indanone (5?-hydroxy-methylhexahydro-1-indanone propionate; 5OH-HIP). Interestingly, RE1?ipdAB and RE1?fadE30, but not RE1?fadA6, also displayed an attenuated phenotype in a macrophage infection assay. Gene products important for growth on 5OH-HIP, as part of the steroid catabolic pathway, thus appear to act as factors involved in the pathogenicity of R. equi. Challenge experiments showed that RE1?ipdAB could be safely administered intratracheally to 2 to 5 week-old foals and oral immunization of foals even elicited a substantial protective immunity against a virulent R. equi strain. Our data show that genes involved in steroid catabolism are promising targets for the development of a live-attenuated vaccine against R. equi infections. PMID:21901092

  10. IDENTIFYING DISEASE RESISTANCE GENES AND PATHWAYS THROUGH HOST-PATHOGEN PROTEIN INTERACTIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major objective of both animal and plant genomics research is to identify disease resistance genes and pathways. Popular approaches to achieve this goal include candidate gene testing, genome-wide QTL screens, and DNA microarrays. We argue that the two-hybrid assay, which detects protein-protein...

  11. The role of phenylpropanoid pathway metabolites in resistance of sorghum to pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sorghum is being developed for diverse uses, including for bioenergy and food. In order to increase efficiency of ethanol production from plant materials, sorghum lines with reduced lignin were developed by incorporating two mutations in lignin biosynthesis pathway genes: brown midrib (bmr) 6 and bm...

  12. Conidial Dihydroxynaphthalene Melanin of the Human Pathogenic Fungus Aspergillus fumigatus Interferes with the Host Endocytosis Pathway.

    PubMed

    Thywißen, Andreas; Heinekamp, Thorsten; Dahse, Hans-Martin; Schmaler-Ripcke, Jeannette; Nietzsche, Sandor; Zipfel, Peter F; Brakhage, Axel A

    2011-01-01

    Aspergillus fumigatus is the most important air-borne fungal pathogen of humans. The interaction of the pathogen with the host's immune system represents a key process to understand pathogenicity. For elimination of invading microorganisms, they need to be efficiently phagocytosed and located in acidified phagolysosomes. However, as shown previously, A. fumigatus is able to manipulate the formation of functional phagolysosomes. Here, we demonstrate that in contrast to pigmentless pksP mutant conidia of A. fumigatus, the gray-green wild-type conidia inhibit the acidification of phagolysosomes of alveolar macrophages, monocyte-derived macrophages, and human neutrophil granulocytes. Therefore, this inhibition is independent of the cell type and applies to the major immune effector cells required for defense against A. fumigatus. Studies with melanin ghosts indicate that the inhibitory effect of wild-type conidia is due to their dihydroxynaphthalene (DHN)-melanin covering the conidia, whereas the hydrophobin RodA rodlet layer plays no role in this process. This is also supported by the observation that pksP conidia still exhibit the RodA hydrophobin layer, as shown by scanning electron microscopy. Mutants defective in different steps of the DHN-melanin biosynthesis showed stronger inhibition than pksP mutant conidia but lower inhibition than wild-type conidia. Moreover, A. fumigatus and A. flavus led to a stronger inhibition of phagolysosomal acidification than A. nidulans and A. terreus. These data indicate that a certain type of DHN-melanin that is different in the various Aspergillus species, is required for maximal inhibition of phagolysosomal acidification. Finally, we identified the vacuolar ATPase (vATPase) as potential target for A. fumigatus based on the finding that addition of bafilomycin which inhibits vATPase, led to complete inhibition of the acidification whereas the fusion of phagosomes containing wild-type conidia and lysosomes was not affected. PMID:21747802

  13. Highly Pathogenic H5N1 Avian Influenza: Entry Pathways into North America via Bird Migration

    PubMed Central

    Peterson, A. Townsend; Benz, Brett W.; Pape?, Monica

    2007-01-01

    Given the possibility of highly pathogenic H5N1 avian influenza arriving in North America and monitoring programs that have been established to detect and track it, we review intercontinental movements of birds. We divided 157 bird species showing regular intercontinental movements into four groups based on patterns of movement—one of these groups (breed Holarctic, winter Eurasia) fits well with the design of the monitoring programs (i.e., western Alaska), but the other groups have quite different movement patterns, which would suggest the importance of H5N1 monitoring along the Pacific, Atlantic, and Gulf coasts of North America. PMID:17330144

  14. A nitrogen response pathway regulates virulence in plant pathogenic fungi: role of TOR and the bZIP protein MeaB.

    PubMed

    López-Berges, Manuel S; Rispail, Nicolas; Prados-Rosales, Rafael C; Di Pietro, Antonio

    2010-12-01

    Virulence in plant pathogenic fungi is controlled through a variety of cellular pathways in response to the host environment. Nitrogen limitation has been proposed to act as a key signal to trigger the in planta expression of virulence genes. Moreover, a conserved Pathogenicity mitogen activated protein kinase (MAPK) cascade is strictly required for plant infection in a wide range of pathogens. We investigated the relationship between nitrogen signaling and the Pathogenicity MAPK cascade in controlling infectious growth of the vascular wilt fungus Fusarium oxysporum. Several MAPK-activated virulence functions such as invasive growth, vegetative hyphal fusion and host adhesion were strongly repressed in the presence of the preferred nitrogen source ammonium. Repression of these functions by ammonium was abolished by L-Methionine sulfoximine (MSX) or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR (Target Of Rapamycin), respectively, and was dependent on the bZIP protein MeaB. Supplying tomato plants with ammonium rather than nitrate resulted in a significant delay of vascular wilt symptoms caused by the F. oxysporum wild type strain, but not by the ?meaB mutant. Ammonium also repressed invasive growth in two other pathogens, the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. Our results suggest the presence of a conserved nitrogen-responsive pathway that operates via TOR and MeaB to control infectious growth in plant pathogenic fungi. PMID:21139428

  15. Linkage of cold acclimation and disease resistance through plant-pathogen interaction pathway in Vitis amurensis grapevine.

    PubMed

    Wu, Jiao; Zhang, Yali; Yin, Ling; Qu, Junjie; Lu, Jiang

    2014-12-01

    Low temperatures cause severe damage to none cold hardy grapevines. A preliminary survey with Solexa sequencing technology was used to analyze gene expression profiles of cold hardy Vitis amurensis 'Zuoshan-1' after cold acclimation at 4 °C for 48 h. A total of 16,750 and 18,068 putative genes were annotated for 4 °C-treated and control library, respectively. Among them, 393 genes were upregulated for at least 20-fold, while 69 genes were downregulated for at least 20-fold under the 4 °C treatment for 48 h. A subset of 101 genes from this survey was investigated further using reverse transcription polymerase chain reaction (RT-PCR). Genes associated with signaling events in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), including generation of calcium signals (CNGC, CMLs), jasmonic acid signal (JAZ1), oxidative burst (Rboh), and phosphorylation (FLS2, BAK, MEKK1, MKKs) cascades, were upregulated after cold acclimation. Disease resistance genes (RPM1, RPS5, RIN4, PBS1) in the process of effector-triggered immunity (ETI) were also upregulated in the current condition. Defense-related genes (WRKYs, PR1, MIN7) involved in both PTI and ETI processes were abundantly expressed after cold acclimation. Our results indicated that plant-pathogen interaction pathways were linked to the cold acclimation in V. amurensis grapevine. Other biotic- and abiotic-related genes, such as defense (protein phosphatase 2C, U-box domain proteins, NCED1, stilbene synthase), transcription (DREBs, MYBs, ERFs, ZFPs), signal transduction (kinase, calcium, and auxin signaling), transport (ATP-binding cassette (ABC) transporters, auxin:hydrogen symporter), and various metabolism, were also abundantly expressed in the cold acclimation of V. Amurensis 'Zuoshan-1' grapevine. This study revealed a series of critical genes and pathways to delineate important biological processes affected by low temperature in 'Zuoshan-1'. PMID:25154381

  16. Evidence of novel pathogenic pathways for the formation of antigastric autoantibodies in Helicobacter pylori gastritis.

    PubMed

    Faller, G; Steininger, H; Appelmelk, B; Kirchner, T

    1998-03-01

    Autoantibodies against gastric epithelial cells are detectable in up to 50% of patients with chronic, active Helicobacter pylori gastritis. Presence of autoantibodies against canalicular structures within human parietal cells (anticanalicular autoantibodies) correlate with gastric mucosa atrophy. It has been suggested, that molecular mimicry between H pylori and the host on the level of Lewis X and Lewis Y blood group antigens leads to these autoantibodies. This study aimed at analysing whether antigastric antibodies can be absorbed to Lewis X or Y positive H pylori strains. Sera from 14 H pylori infected patients with anticanalicular autoantibodies were effectively absorbed to H pylori. Immunohistochemical studies of the absorbed sera showed no decrease of antigastric autoreactivity. Pathogenic mechanisms other than molecular mimicry lead to the formation of antigastric autoantibodies, and epitopes other than Lewis antigens are the autoimmune targets. PMID:9659270

  17. Towards defining a rigidity-associated pathogenic pathway in idiopathic parkinsonism.

    PubMed

    Dobbs, R John; Charlett, André; Dobbs, Sylvia M; Weller, Clive; Iguodala, Owens; Smee, Cori; Bowthorpe, James; Taylor, David; Bjarnason, Ingvar T

    2012-01-01

    Helicobacter pylori eradication has a differential effect on the facets of idiopathic parkinsonism (IP): brady/hypokinesia improves, but rigidity worsens. Small intestinal bacterial overgrowth is common in IP and has been described as a sequel to Helicobacter eradication. The hyperhomocysteinaemia of IP is, in part, explained by serum vitamin B(12), but the concentration is not explained by Helicobacter status. Moreover, Helicobacter-associated gastric atrophy is uncommon in IP. However, overgrowth both increases B(12) utilization and provides a source of inflammation to drive homocysteine production. It is not a bystander event in IP: clouds of lysosomes are seen in duodenal enterocytes. Its candidature for causality of a rigidity-associated pathway is circumstantial: there are biological gradients of rigidity on natural killer and T-helper blood counts, both being higher with hydrogen breath test positivity for overgrowth. PMID:22205039

  18. MAP kinase signalling pathway components and targets conserved between the distantly related plant pathogenic fungi Mycosphaerella graminicola and Magnaporthe grisea.

    PubMed

    Kramer, Bastian; Thines, Eckhard; Foster, Andrew J

    2009-09-01

    Mycosphaerella graminicola is a dimorphic fungus which causes Septoria tritici leaf blotch. This report describes the examination of the role of several components of the Pmk1p/Fus3p mitogen-activated protein kinase (MAPK) signalling pathway in the development of this species. The genes encoding the MAPK kinase kinase MgSte11p and the MAPK kinase MgSte7p were found to be indispensible for pathogenicity while the deletion of the gene encoding the proposed scaffold protein MgSte50p led to a reduction in virulence. These phenotypes were attributed to a reduced ability to form filaments on the plant surface which prevented penetration. A delayed disease progression was observed on deletion of the gene MGSTE12. The MGSTE7, MGSTE50 and MGSTE12 genes were able to complement mutants of Magnaporthe grisea lacking the orthologous genes. Interactions between the My. graminicola signalling components were also investigated. Furthermore genes whose MgSte12p/Mst12p dependence is conserved between My. graminicola and Ma. grisea were identified. PMID:19520179

  19. Endoscopic dacryocystorhinostomy as treatment for lower lacrimal pathway obstructions in adults: Review article.

    PubMed

    Penttilä, Elina; Smirnov, Grigori; Tuomilehto, Henri; Kaarniranta, Kai; Seppä, Juha

    2015-01-01

    Obstruction of the lacrimal pathway is manifested by epiphora, infection, and blurred vision as well as ocular and facial pain. Conservative treatments only achieve temporary relief of symptoms, thus surgery is the treatment of choice. Dacryocystorhinostomy (DCR) is recognized as the most suitable treatment for patients with obstructions of the lacrimal system at the level of the sac or in the nasolacrimal duct. The aim of this operation is to create a bypass between the lacrimal sac and the nasal cavity. During the past 2 decades, advances in rigid endoscopic equipment and other instruments have made it possible to obtain more information about the anatomic landmarks of the nasolacrimal system, which led to the development of less-invasive and safer endoscopic techniques. However, many parts of the treatment process related to endoscopic endonasal dacryocystorhinostomy (EN-DCR) still remain controversial. This article reviews the published literature about the technical issues associated with the success of EN-DCR, and clarifies the pros and cons of different pre- and postoperative procedures in adults with lower lacrimal pathway obstructions. PMID:25860166

  20. Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway.

    PubMed

    Kaplan, Allen P; Joseph, Kusumam

    2014-01-01

    Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikrein and kallikrein cleaves high molecular weight kininogen (HK) to release bradykinin. A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein (kallikrein-feedback) and sequential cleavage yields two forms of activated factor XII; namely, factor XIIa followed by factor XII fragment (factor XIIf). PK circulates bound to HK and binding induces a conformational change in PK so that it acquires enzymatic activity and can stoichiometrically cleave HK to produce bradykinin. This reaction is prevented from occurring in plasma by the presence of C1 inhibitor (C1 INH). The same active site leads to autoactivation of the PK-HK complex to generate kallikrein if a phosphate containing buffer is used. Theoretically, formation of kallikrein by this factor XII-independent route can activate surface-bound factor XII to generate factor XIIa resulting in a marked increase in the rate of bradykinin formation as stoichiometric reactions are replaced by Michaelis-Menton, enzyme-substrate, kinetics. Zinc-dependent binding of the constituents of the bradykinin-forming cascade to the surface of endothelial cells is mediated by gC1qR and bimolecular complexes of gC1qR-cytokeratin 1 and cytokeratin 1-u-PAR (urokinase plasminogen activator receptor). Factor XII and HK compete for binding to free gC1qR (present in excess) while cytokeratin 1-u-PAR preferentially binds factor XII and gC1qR-cytokeratin 1 preferentially binds HK. Autoactivation of factor XII can be initiated as a result of binding to gC1qR but is prevented by C1 INH. Yet stoichiometric activation of PK-HK to yield kallikrein in the absence of factor XII can be initiated by heat shock protein 90 (HSP-90) which forms a zinc-dependent trimolecular complex by binding to HK. Thus, endothelial cell-dependent activation can be initiated by activation of factor XII or by activation of PK-HK. Hereditary angioedema (HAE), types I and II, are due to autosomal dominant mutations of the C1 INH gene. In type I disease, the level of C1 INH protein and function is proportionately low, while type II disease has a normal protein level but diminished function. There is trans-inhibition of the one normal gene so that functional levels are 30% or less and severe angioedema affecting peripheral structures, the gastrointestinal tract, and the larynx results. Prolonged incubation of plasma of HAE patients (but not normal controls) leads to bradykinin formation and conversion of PK to kallikrein which is reversed by reconstitution with C1 INH. The disorder can be treated by C1 INH replacement, inhibition of plasma kallikrein, or blockade at the bradykinin B-2 receptor. A recently described HAE with normal C1 INH (based on inhibition of activated C1s) presents similarly; the defect is not yet clear, however one-third of patients have a mutant factor XII gene. We have shown that this HAE has a defect in bradykinin overproduction whether the factor XII mutation is present or not, that patients' C1 INH is capable of inhibiting factor XIIa and kallikrein (and not just activated C1) but the functional level is approximately 40-60% of normal, and that ?2 macroglobulin protein levels are normal. In vitro abnormalities can be suppressed by raising C1 INH to twice normal levels. Finally, aggregated proteins have been shown to activate the bradykinin-forming pathway by catalyzing factor XII autoactivation. Those include the amyloid ? protein of Alzheimer's disease and cryoglobulins. This may represent a new avenue for kinin-dependent research in human disease. In allergy (anaphylaxis; perhaps other mast cell-dependent reactions), the oversulfated proteoglycan of mast cells, liberated along with histamine, also catalyze factor XII autoactivation. PMID:24388213

  1. Gene expression analysis of potential genes and pathways involved in the pathogenic mechanisms of parvovirus B19 in human colorectal cancer

    PubMed Central

    ZHANG, WEI-PING; YANG, HUA; CHEN, HONG; ZHU, HAI-RONG; LEI, QUAN; SONG, YUN-HONG; DAI, ZHONG-MING; SUN, JING-SHAN; JIANG, LI-LI; NIE, ZHAN-GUO

    2014-01-01

    In order to investigate the pathogenic mechanisms of parvovirus B19 in human colorectal cancer, plasmids containing the VP1 or VP2 viral capsid proteins or the NS1 non-structural proteins of parvovirus B19 were constructed and transfected into primary human colorectal epithelial cells and LoVo cells. Differential gene expression was detected using a human genome expression array. Functional gene annotation analyses were performed using Database for Annotation, Visualization and Integrated Discovery v6.7 software. Gene ontology (GO) analyses revealed that VP1-related functions included the immune response, immune system process, defense response and the response to stimulus, while NS1-associated functions were found to include organelle fission, nuclear division, mitosis, the M-phase of the mitotic cell cycle, the mitotic cell cycle, M-phase, cell cycle phase, cell cycle process and cell division. Pathway expression analysis revealed that VP1-associated pathways included cell adhesion molecules, antigen processing and presentation, cytokines and the inflammatory response. Moreover, NS1-associated pathways included the cell cycle, pathways in cancer, colorectal cancer, the wnt signaling pathway and focal adhesion. Among the differential genes detected in the present study, 12 genes were found to participate in general cancer pathways and six genes were observed to participate in colorectal cancer pathways. NS1 is a key molecule in the pathogenic mechanism of parvovirus B19 in colorectal cancer. Several GO categories, pathways and genes were selected and may be the key targets through which parvovirus B19 participates in colorectal cancer pathogenesis. PMID:25013465

  2. The High-Osmolarity Glycerol Response Pathway in the Human Fungal Pathogen Candida glabrata Strain ATCC 2001 Lacks a Signaling Branch That Operates in Baker's Yeast

    Microsoft Academic Search

    Christa Gregori; Christoph Schuller; Andreas Roetzer; Tobias Schwarzmuller; Gustav Ammerer; Karl Kuchler

    2007-01-01

    The high-osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway mediates adaptation to high-osmolarity stress in the yeast Saccharomyces cerevisiae. Here we investigate the function of HOG in the human opportunistic fungal pathogen Candida glabrata. C. glabrata sho1 (Cgsho1) deletion strains from the sequenced ATCC 2001 strain display severe growth defects under hyperosmotic conditions, a phenotype not observed for yeast sho1

  3. Pathogen signatures activate a ubiquitinylation pathway that modulates function of the metabolic checkpoint kinase mTOR

    PubMed Central

    Ivanov, Stanimir S.; Roy, Craig R.

    2013-01-01

    The mammalian immune system has the ability to discriminate between pathogenic and non-pathogenic microbes to control inflammation. Here we investigated ubiquitinylation profiles of host proteins after infection of macrophages with a virulent strain of the intracellular bacterium Legionella pneumophila and a non-pathogenic mutant. Only infection with pathogenic Legionella resulted in ubiquitinylation of positive regulators of the metabolic checkpoint kinase mTOR leading to diminished mTOR activity. Detection of pathogen signatures resulted in translational biasing to proinflammatory cytokines through mTOR-mediated regulation of cap-dependent translation. Thus, there is a pathogen detection program in macrophages that stimulates protein ubiquitinylation and degradation of mTOR regulators, which suppresses mTOR function and directs a proinflammatory cytokine program. PMID:24121838

  4. Bacterial Pathogens Induce Abscess Formation by CD4+ T-Cell Activation via the CD28–B7-2 Costimulatory Pathway

    PubMed Central

    Tzianabos, Arthur O.; Chandraker, Anil; Kalka-Moll, Wiltrud; Stingele, Francesca; Dong, Victor M.; Finberg, Robert W.; Peach, Robert; Sayegh, Mohamed H.

    2000-01-01

    Abscesses are a classic host response to infection by many pathogenic bacteria. The immunopathogenesis of this tissue response to infection has not been fully elucidated. Previous studies have suggested that T cells are involved in the pathologic process, but the role of these cells remains unclear. To delineate the mechanism by which T cells mediate abscess formation associated with intra-abdominal sepsis, the role of T-cell activation and the contribution of antigen-presenting cells via CD28-B7 costimulation were investigated. T cells activated in vitro by zwitterionic bacterial polysaccharides (Zps) known to induce abscess formation required CD28-B7 costimulation and, when adoptively transferred to the peritoneal cavity of naïve rats, promoted abscess formation. Blockade of T-cell activation via the CD28-B7 pathway in animals with CTLA4Ig prevented abscess formation following challenge with different bacterial pathogens, including Staphylococcus aureus, Bacteroides fragilis, and a combination of Enterococcus faecium and Bacteroides distasonis. In contrast, these animals had an increased abscess rate following in vivo T-cell activation via CD28 signaling. Abscess formation in vivo and T-cell activation in vitro required costimulation by B7-2 but not B7-1. These results demonstrate that abscess formation by pathogenic bacteria is under the control of a common effector mechanism that requires T-cell activation via the CD28–B7-2 pathway. PMID:11083777

  5. Role of the lpxM lipid A biosynthesis pathway gene in pathogenicity of avian pathogenic Escherichia coli strain E058 in a chicken infection model.

    PubMed

    Xu, Huiqing; Ling, Jielu; Gao, Qingqing; He, Hongbo; Mu, Xiaohui; Yan, Zhen; Gao, Song; Liu, Xiufan

    2013-10-25

    Lipopolysaccharide (LPS) is a major surface component of avian pathogenic Escherichia coli (APEC), and is a possible virulence factor in avian infections caused by this organism. The contribution of the lpxM gene, which encodes a myristoyl transferase that catalyzes the final step in lipid A biosynthesis, to the pathogenicity of APEC has not previously been assessed. In this study, an isogenic lpxM mutant, E058?lpxM, was constructed in APEC O2 strain E058 and then characterized. Structural analysis of lipid A from the parental strain and derived mutant showed that E058?lpxM lacked one myristoyl (C14:0) on its lipid A molecules. No differences were observed between the mutant and wild-type in a series of tests including growth rate in different broths and ability to survive in specific-pathogen-free chicken serum. However, the mutant showed significantly reduced invasion and intracellular survival in the avian macrophage HD11 cell line (P<0.05). Nitric oxide production reduction (P<0.05) and cytokine gene expression downregulation (P<0.05 or P<0.01) also showed in HD11 treated with E058?lpxM-derived LPS compared with that in cells treated with E058-derived LPS at different times. Compared to the parental strain E058, E058?lpxM had a significant reduction in bacterial load in heart (P<0.01), liver (P<0.01), spleen (P<0.01), lung (P<0.05), and kidney (P<0.05) tissues. The histopathological lesions in visceral organs of birds challenged with the wild-type strain were more severe than in birds infected with the mutant. However, the E058?lpxM mutant showed a similar sensitivity pattern to the parental strain following exposure to several hydrophobic reagents. These results indicate that the lpxM gene is important for the pathogenicity and biological activity of APEC strain E058. PMID:23856328

  6. Elucidation of the pathways responsible for the biosynthesis of UDP-N,N'-diacetylbacillosamine in bacterial pathogens

    E-print Network

    Morrison, Michael James

    2014-01-01

    The highly-modified, bacterial sugar N,N'-diacetylbacillosamine (diNAcBac) has been implicated in the pathogenicity of certain microbes through its incorporation onto various protein virulence factors. In particular, ...

  7. Pattern Triggered Immunity (PTI) in Tobacco: Isolation of Activated Genes Suggests Role of the Phenylpropanoid Pathway in Inhibition of Bacterial Pathogens

    PubMed Central

    Szatmári, Ágnes; Zvara, Ágnes; Móricz, Ágnes M.; Besenyei, Eszter; Szabó, Erika; Ott, Péter G.; Puskás, László G.; Bozsó, Zoltán

    2014-01-01

    Background Pattern Triggered Immunity (PTI) or Basal Resistance (BR) is a potent, symptomless form of plant resistance. Upon inoculation of a plant with non-pathogens or pathogenicity-mutant bacteria, the induced PTI will prevent bacterial proliferation. Developed PTI is also able to protect the plant from disease or HR (Hypersensitive Response) after a challenging infection with pathogenic bacteria. Our aim was to reveal those PTI-related genes of tobacco (Nicotiana tabacum) that could possibly play a role in the protection of the plant from disease. Methodology/Principal Findings Leaves were infiltrated with Pseudomonas syringae pv. syringae hrcC- mutant bacteria to induce PTI, and samples were taken 6 and 48 hours later. Subtraction Suppressive Hybridization (SSH) resulted in 156 PTI-activated genes. A cDNA microarray was generated from the SSH clone library. Analysis of hybridization data showed that in the early (6 hpi) phase of PTI, among others, genes of peroxidases, signalling elements, heat shock proteins and secondary metabolites were upregulated, while at the late phase (48 hpi) the group of proteolysis genes was newly activated. Microarray data were verified by real time RT-PCR analysis. Almost all members of the phenyl-propanoid pathway (PPP) possibly leading to lignin biosynthesis were activated. Specific inhibition of cinnamic-acid-4-hydroxylase (C4H), rate limiting enzyme of the PPP, decreased the strength of PTI - as shown by the HR-inhibition and electrolyte leakage tests. Quantification of cinnamate and p-coumarate by thin-layer chromatography (TLC)-densitometry supported specific changes in the levels of these metabolites upon elicitation of PTI. Conclusions/Significance We believe to provide first report on PTI-related changes in the levels of these PPP metabolites. Results implicated an actual role of the upregulation of the phenylpropanoid pathway in the inhibition of bacterial pathogenic activity during PTI. PMID:25101956

  8. A large, mobile pathogenicity island confers plant pathogenicity on Streptomyces species.

    PubMed

    Kers, Johan A; Cameron, Kimberly D; Joshi, Madhumita V; Bukhalid, Raghida A; Morello, Joanne E; Wach, Michael J; Gibson, Donna M; Loria, Rosemary

    2005-02-01

    Potato scab is a globally important disease caused by polyphyletic plant pathogenic Streptomyces species. Streptomyces acidiscabies, Streptomyces scabies and Streptomyces turgidiscabies possess a conserved biosynthetic pathway for the nitrated dipeptide phytotoxin thaxtomin. These pathogens also possess the nec1 gene which encodes a necrogenic protein that is an independent virulence factor. In this article we describe a large (325-660 kb) pathogenicity island (PAI) conserved among these three plant pathogenic Streptomyces species. A partial DNA sequence of this PAI revealed the thaxtomin biosynthetic pathway, nec1, a putative tomatinase gene, and many mobile genetic elements. In addition, the PAI from S. turgidiscabies contains a plant fasciation (fas) operon homologous to and colinear with the fas operon in the plant pathogen Rhodococcus fascians. The PAI was mobilized during mating from S. turgidiscabies to the non-pathogens Streptomyces coelicolor and Streptomyces diastatochromogenes on a 660 kb DNA element and integrated site-specifically into a putative integral membrane lipid kinase. Acquisition of the PAI conferred a pathogenic phenotype on S. diastatochromogenes but not on S. coelicolor. This PAI is the first to be described in a Gram-positive plant pathogenic bacterium and is responsible for the emergence of new plant pathogenic Streptomyces species in agricultural systems. PMID:15686551

  9. Identification of possible pathogenic pathways in Behçet's disease using genome-wide association study data from two different populations.

    PubMed

    Bakir-Gungor, Burcu; Remmers, Elaine F; Meguro, Akira; Mizuki, Nobuhisa; Kastner, Daniel L; Gul, Ahmet; Sezerman, Osman U

    2015-05-01

    Behçet's disease (BD) is a multi-system inflammatory disorder of unknown etiology. Two recent genome-wide association studies (GWASs) of BD confirmed a strong association with the MHC class I region and identified two non-HLA common genetic variations. In complex diseases, multiple factors may target different sets of genes in the same pathway and thus may cause the same disease phenotype. We therefore hypothesized that identification of disease-associated pathways is critical to elucidate mechanisms underlying BD, and those pathways may be conserved within and across populations. To identify the disease-associated pathways, we developed a novel methodology that combines nominally significant evidence of genetic association with current knowledge of biochemical pathways, protein-protein interaction networks, and functional information of selected SNPs. Using this methodology, we searched for the disease-related pathways in two BD GWASs in Turkish and Japanese case-control groups. We found that 6 of the top 10 identified pathways in both populations were overlapping, even though there were few significantly conserved SNPs/genes within and between populations. The probability of random occurrence of such an event was 2.24E-39. These shared pathways were focal adhesion, MAPK signaling, TGF-? signaling, ECM-receptor interaction, complement and coagulation cascades, and proteasome pathways. Even though each individual has a unique combination of factors involved in their disease development, the targeted pathways are expected to be mostly the same. Hence, the identification of shared pathways between the Turkish and the Japanese patients using GWAS data may help further elucidate the inflammatory mechanisms in BD pathogenesis. PMID:25227143

  10. In Vitro Studies on the Antimicrobial Peptide Human Beta-Defensin 9 (HBD9): Signalling Pathways and Pathogen-Related Response (An American Ophthalmological Society Thesis)

    PubMed Central

    Dua, Harminder S.; Otri, Ahmad Muneer; Hopkinson, Andrew; Mohammed, Imran

    2014-01-01

    Purpose: Human ?-defensins (HBDs) are an important part of the innate immune host defense at the ocular surface. Unlike other defensins, expression of HBD9 at the ocular surface is reduced during microbial infection, but activation of toll-like receptor 2 (TLR2) in corneal epithelial cells has been shown to up-regulate HBD9. Our purpose was to test the hypothesis that TLR2 has a key role in the signalling pathway(s) involved in the overexpression or underexpression of HBD9, and accordingly, different pathogens would induce a different expression pattern of HBD9. Methods: The in vitro RNAi silencing method and response to dexamethasone were used to determine key molecules involved in signalling pathways of HBD9 in immortalized human corneal epithelial cells. The techniques included cell culture with exposure to specific transcription factor inhibitors and bacteria, RNA extraction and cDNA synthesis, quantitative real-time polymerase chain reaction, and immunohistology. Results: This study demonstrates that TLR2 induces HBD9 mRNA and protein expression in a time- and dose-dependent manner. Transforming growth factor-?–activated kinase 1 (TAK1) plays a central role in HBD9 induction by TLR2, and transcription factors c-JUN and activating transcription factor 2 are also involved. Dexamethasone reduces TLR2-mediated up-regulation of HBD9 mRNA and protein levels in mitogen-activated protein kinase phosphatase 1 (MKP1)-dependent and c-JUN-independent manner. HBD9 expression differs with gram-negative and gram-positive bacteria. Conclusions: TLR2-mediated MKPs and nuclear factor-?B signalling pathways are involved in HBD9 expression. TAK-1 is a key molecule. These molecules can be potentially targeted to modulate HBD9 expression. Differential expression of HBD9 with different bacteria could be related to differences in pathogen-associated molecular patterns of these organisms. PMID:25646028

  11. Identification of Metabolic Pathways Expressed by Pichia anomala Kh6 in the Presence of the Pathogen Botrytis cinerea on Apple: New Possible Targets for Biocontrol Improvement

    PubMed Central

    Kwasiborski, Anthony; Bajji, Mohammed; Renaut, Jenny; Delaplace, Pierre; Jijakli, M. Haissam

    2014-01-01

    Yeast Pichia anomala strain Kh6 Kurtzman (Saccharomycetales: Endomycetaceae) exhibits biological control properties that provide an alternative to the chemical fungicides currently used by fruit or vegetable producers against main post-harvest pathogens, such as Botrytis cinerea (Helotiales: Sclerotiniaceae). Using an in situ model that takes into account interactions between organisms and a proteomic approach, we aimed to identify P. anomala metabolic pathways influenced by the presence of B. cinerea. A total of 105 and 60 P. anomala proteins were differentially represented in the exponential and stationary growth phases, respectively. In the exponential phase and in the presence of B. cinerea, the pentose phosphate pathway seems to be enhanced and would provide P. anomala with the needed nucleic acids and energy for the wound colonisation. In the stationary phase, P. anomala would use alcoholic fermentation both in the absence and presence of the pathogen. These results would suggest that the competitive colonisation of apple wounds could be implicated in the mode of action of P. anomala against B. cinerea. PMID:24614090

  12. Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: activation of signal transduction pathways and perturbations of intestinal absorption and secretion.

    PubMed

    Fantini, J; Maresca, M; Hammache, D; Yahi, N; Delézay, O

    2000-01-01

    Glycosphingolipid (GSL)-enriched microdomains are used as cellular binding sites for various pathogens including viruses and bacteria. These attachment platforms are specifically associated with transducer molecules, so that the binding of host pathogens (or their toxins) to the cell surface may result in the activation of signal transduction pathways. In the intestinal epithelium, such pathogen-induced dysregulations of signal transduction can elicit a severe impairment of enterocytic functions. In this study, we demonstrate that the interaction of a bacterial toxin (cholera toxin) and a viral envelope glycoprotein (HIV-1 gp120) with the apical plasma membrane of intestinal cells is mediated by GSL-enriched microdomains that are associated with G regulatory proteins. These microbial proteins induce a GSL-dependent increase of intestinal fluid secretion by two mechanisms: activation of chloride secretion and inhibition of Na+ -dependent glucose absorption. Taken together, these data support the view that GSL-enriched microdomains in the apical plasma membrane of enterocytes are involved in the regulation of intestinal functions. PMID:11201788

  13. Biosecurity and Vector Behaviour: Evaluating the Potential Threat Posed by Anglers and Canoeists as Pathways for the Spread of Invasive Non-Native Species and Pathogens

    PubMed Central

    Anderson, Lucy G.; White, Piran C. L.; Stebbing, Paul D.; Stentiford, Grant D.; Dunn, Alison M.

    2014-01-01

    Invasive non-native species (INNS) endanger native biodiversity and are a major economic problem. The management of pathways to prevent their introduction and establishment is a key target in the Convention on Biological Diversity's Aichi biodiversity targets for 2020. Freshwater environments are particularly susceptible to invasions as they are exposed to multiple introduction pathways, including non-native fish stocking and the release of boat ballast water. Since many freshwater INNS and aquatic pathogens can survive for several days in damp environments, there is potential for transport between water catchments on the equipment used by recreational anglers and canoeists. To quantify this biosecurity risk, we conducted an online questionnaire with 960 anglers and 599 canoeists to investigate their locations of activity, equipment used, and how frequently equipment was cleaned and/or dried after use. Anglers were also asked about their use and disposal of live bait. Our results indicate that 64% of anglers and 78.5% of canoeists use their equipment/boat in more than one catchment within a fortnight, the survival time of many of the INNS and pathogens considered in this study and that 12% of anglers and 50% of canoeists do so without either cleaning or drying their kit between uses. Furthermore, 8% of anglers and 28% of canoeists had used their equipment overseas without cleaning or drying it after each use which could facilitate both the introduction and secondary spread of INNS in the UK. Our results provide a baseline against which to evaluate the effectiveness of future biosecurity awareness campaigns, and identify groups to target with biosecurity awareness information. Our results also indicate that the biosecurity practices of these groups must improve to reduce the likelihood of inadvertently spreading INNS and pathogens through these activities. PMID:24717714

  14. Biosecurity and vector behaviour: evaluating the potential threat posed by anglers and canoeists as pathways for the spread of invasive non-native species and pathogens.

    PubMed

    Anderson, Lucy G; White, Piran C L; Stebbing, Paul D; Stentiford, Grant D; Dunn, Alison M

    2014-01-01

    Invasive non-native species (INNS) endanger native biodiversity and are a major economic problem. The management of pathways to prevent their introduction and establishment is a key target in the Convention on Biological Diversity's Aichi biodiversity targets for 2020. Freshwater environments are particularly susceptible to invasions as they are exposed to multiple introduction pathways, including non-native fish stocking and the release of boat ballast water. Since many freshwater INNS and aquatic pathogens can survive for several days in damp environments, there is potential for transport between water catchments on the equipment used by recreational anglers and canoeists. To quantify this biosecurity risk, we conducted an online questionnaire with 960 anglers and 599 canoeists to investigate their locations of activity, equipment used, and how frequently equipment was cleaned and/or dried after use. Anglers were also asked about their use and disposal of live bait. Our results indicate that 64% of anglers and 78.5% of canoeists use their equipment/boat in more than one catchment within a fortnight, the survival time of many of the INNS and pathogens considered in this study and that 12% of anglers and 50% of canoeists do so without either cleaning or drying their kit between uses. Furthermore, 8% of anglers and 28% of canoeists had used their equipment overseas without cleaning or drying it after each use which could facilitate both the introduction and secondary spread of INNS in the UK. Our results provide a baseline against which to evaluate the effectiveness of future biosecurity awareness campaigns, and identify groups to target with biosecurity awareness information. Our results also indicate that the biosecurity practices of these groups must improve to reduce the likelihood of inadvertently spreading INNS and pathogens through these activities. PMID:24717714

  15. G(alpha) and Gbeta proteins regulate the cyclic AMP pathway that is required for development and pathogenicity of the phytopathogen Mycosphaerella graminicola.

    PubMed

    Mehrabi, Rahim; Ben M'Barek, Sarrah; van der Lee, Theo A J; Waalwijk, Cees; de Wit, Pierre J G M; Kema, Gerrit H J

    2009-07-01

    We identified and functionally characterized genes encoding three Galpha proteins and one Gbeta protein in the dimorphic fungal wheat pathogen Mycosphaerella graminicola, which we designated MgGpa1, MgGpa2, MgGpa3, and MgGpb1, respectively. Sequence comparisons and phylogenetic analyses showed that MgGPA1 and MgGPA3 are most related to the mammalian Galpha(i) and Galpha(s) families, respectively, whereas MgGPA2 is not related to either of these families. On potato dextrose agar (PDA) and in yeast glucose broth (YGB), MgGpa1 mutants produced significantly longer spores than those of the wild type (WT), and these developed into unique fluffy mycelia in the latter medium, indicating that this gene negatively controls filamentation. MgGpa3 mutants showed more pronounced yeast-like growth accompanied with hampered filamentation and secreted a dark-brown pigment into YGB. Germ tubes emerging from spores of MgGpb1 mutants were wavy on water agar and showed a nested type of growth on PDA that was due to hampered filamentation, numerous cell fusions, and increased anastomosis. Intracellular cyclic AMP (cAMP) levels of MgGpb1 and MgGpa3 mutants were decreased, indicating that both genes positively regulate the cAMP pathway, which was confirmed because the WT phenotype was restored by adding cAMP to these mutant cultures. The cAMP levels in MgGpa1 mutants and the WT were not significantly different, suggesting that this gene might be dispensable for cAMP regulation. In planta assays showed that mutants of MgGpa1, MgGpa3, and MgGpb1 are strongly reduced in pathogenicity. We concluded that the heterotrimeric G proteins encoded by MgGpa3 and MgGpb1 regulate the cAMP pathway that is required for development and pathogenicity in M. graminicola. PMID:19411619

  16. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin.

    PubMed

    Loveday, Emma-Kate; Diederich, Sandra; Pasick, John; Jean, François

    2015-01-01

    A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions. PMID:25234642

  17. GENIES: a natural-language processing system for the extraction of molecular pathways from journal articles

    Microsoft Academic Search

    Carol Friedman; Pauline Kra; Hong Yu; Michael Krauthammer; Andrey Rzhetsky

    2001-01-01

    Systems that extract structured information from natural language passages have been highly successful in specialized domains. The time is opportune for devel- oping analogous applications for molecular biology and genomics. We present a system, GENIES, that extracts and structures information about cellular pathways from the biological literature in accordance with a knowledge model that we developed earlier. We implemented GENIES

  18. ARTICLE IN PRESS The folding pathway of ubiquitin from all-atom

    E-print Network

    Jackson, Sophie

    all-atom molecular dynamics simulations. We dissect the folding pathway using two techniques: first properties that we look at are hydrophobic solvent accessible surface area (SASA) and Ca of secondary structure arrangement. Analysis of the structure of the intermediate state shows

  19. Pathogen-induced systemic activation of a plant defensin gene in Arabidopsis follows a salicylic acid-independent pathway.

    PubMed Central

    Penninckx, I A; Eggermont, K; Terras, F R; Thomma, B P; De Samblanx, G W; Buchala, A; Métraux, J P; Manners, J M; Broekaert, W F

    1996-01-01

    A 5-kD plant defensin was purified from Arabidopsis leaves challenged with the fungus Alternaria brassicicola and shown to possess antifungal properties in vitro. The corresponding plant defensin gene was induced after treatment of leaves with methyl jasmonate or ethylene but not with salicylic acid or 2,6-dichloroisonicotinic acid. When challenged with A. brassicicola, the levels of the plant defensin protein and mRNA rose both in inoculated leaves and in nontreated leaves of inoculated plants (systemic leaves). These events coincided with an increase in the endogenous jasmonic acid content of both types of leaves. Systemic pathogen-induced expression of the plant defensin gene was unaffected in Arabidopsis transformants (nahG) or mutants (npr1 and cpr1) affected in the salicylic acid response but was strongly reduced in the Arabidopsis mutants eln2 and col1 that are blocked in their response to ethylene and methyl jasmonate, respectively. Our results indicate that systemic pathogen-induced expression of the plant defensin gene in Arabidopsis is independent of salicylic acid but requires components of the ethylene and jasmonic acid response. PMID:8989885

  20. Of truth and pathways: chasing bits of information through myriads of articles

    Microsoft Academic Search

    Michael Krauthammer; Pauline Kra; Ivan Iossifov; Shawn M. Gomez; George Hripcsak; Vasileios Hatzivassiloglou; Carol Friedman; Andrey Rzhetsky

    2002-01-01

    Knowledge on interactions between molecules in living cells is indispensable for theoretical analysis and practical applications in modern genomics and molecular biology. Building such networks relies on the assumption that the correct molecular interactions are known or can be identified by reading a few research articles. However, this assumption does not necessarly hold, as truth is rather an emerging property

  1. Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors.

    PubMed

    Reed, Daniel M; Foldes, Gabor; Gatheral, Timothy; Paschalaki, Koralia E; Lendvai, Zsuzsanna; Bagyura, Zsolt; Nemeth, Tamas; Skopal, Judit; Merkely, Bela; Telcian, Aurica G; Gogsadze, Leila; Edwards, Michael R; Gough, Peter J; Bertin, John; Johnston, Sebastian L; Harding, Sian E; Mitchell, Jane A

    2014-01-01

    Human embryonic stem cell-derived endothelial cells (hESC-EC), as well as other stem cell derived endothelial cells, have a range of applications in cardiovascular research and disease treatment. Endothelial cells sense Gram-negative bacteria via the pattern recognition receptors (PRR) Toll-like receptor (TLR)-4 and nucleotide-binding oligomerisation domain-containing protein (NOD)-1. These pathways are important in terms of sensing infection, but TLR4 is also associated with vascular inflammation and atherosclerosis. Here, we have compared TLR4 and NOD1 responses in hESC-EC with those of endothelial cells derived from other stem cells and with human umbilical vein endothelial cells (HUVEC). HUVEC, endothelial cells derived from blood progenitors (blood outgrowth endothelial cells; BOEC), and from induced pluripotent stem cells all displayed both a TLR4 and NOD1 response. However, hESC-EC had no TLR4 function, but did have functional NOD1 receptors. In vivo conditioning in nude rats did not confer TLR4 expression in hESC-EC. Despite having no TLR4 function, hESC-EC sensed Gram-negative bacteria, a response that was found to be mediated by NOD1 and the associated RIP2 signalling pathways. Thus, hESC-EC are TLR4 deficient but respond to bacteria via NOD1. This data suggests that hESC-EC may be protected from unwanted TLR4-mediated vascular inflammation, thus offering a potential therapeutic advantage. PMID:24690886

  2. MICROBIOLOGY: A Bacterial Pathogen Sees the Light

    NSDL National Science Digital Library

    John T. M. Kennis (Faculty of Sciences, Vrije Universiteit; Biophysics Department)

    2007-08-24

    Access to the article is free, however registration and sign-in are required. Photosensitive proteins abound in the bacterial kingdom, but their cellular functions often remain a mystery. In this Perspective Kennis and Crosson discuss how Swartz et al. identified a functional role for a new type of light sensor in bacteria--light, oxygen, or voltage (LOV) histidine kinase. In the notorious pathogen Brucella abortus, light increases the enzymatic activity of this kinase, which, remarkably, increases virulence of the bacterium. Related LOV histidine kinases are conserved across a range of bacterial taxa, suggesting that this virulence pathway could be one of many new photosensory pathways regulating bacterial physiology.

  3. Siderophore-Based Iron Acquisition and Pathogen Control

    PubMed Central

    Miethke, Marcus; Marahiel, Mohamed A.

    2007-01-01

    Summary: High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed. PMID:17804665

  4. Population genetic analyses provide insights on the introduction pathway and spread patterns of the North American forest pathogen Heterobasidion irregulare in Italy.

    PubMed

    Garbelotto, M; Guglielmo, F; Mascheretti, S; Croucher, P J P; Gonthier, P

    2013-10-01

    A population genetics approach is used to identify the most likely introduction site and introduction pathway for the North American forest pathogen Heterobasidion irregulare using 101 isolates from six sites in Italy and 34 isolates from five sites in North America. Diversity indices based on sequences from ten loci indicate the highest diversity in Italy is found in Castelfusano/Castelporziano and that diversity progressively decreases with increasing distance from that site. AMOVA, Bayesian clustering and principal coordinates analyses based on 12 SSR loci indicate high levels of gene flow among sites, high frequency of admixing, and fail to identify groups of genotypes exclusive to single locations. Cumulatively, these analyses suggest the current infestation is the result of multiple genotypes expanding their range from a single site. Based on two sequenced loci, a single source site in North America could provide enough variability to explain the variability observed in Italy. These results support the notion that H. irregulare was introduced originally in Castelporziano: because Castelporziano has been sealed off from the rest of the world for centuries except for a camp set up by the US military in 1944, we conclude the fungus may have been transported in infected wood used by the military. Finally, spatial autocorrelation analyses using SSR data indicate a significant under-dispersion of alleles up to 0.5-10 km, while a significant overdispersion of alleles was detected at distances over 80 km: these ranges can be used to make predictions on the likely dispersal potential of the invasive pathogen. PMID:24033583

  5. ARTicle

    NSDL National Science Digital Library

    ARTicle is yet another entry in the arena of museum blogs, this time from the Art Institute of Chicago (AIC). ARTicle is intended to cover all sorts of subjects related to the AIC, and its six staff writers ask readers to, "Think of it as a little peek behind the scenes." The blog dates back to October of 2009, and visitors will find recent entries that include a staff picks entry, an entry on saints and symbols, and a short video featuring Robby S., a media assistant in Communications. In the video, Robby discusses Chilean painter Matta's The Earth Is a Man, 1942, which he describes as looking like a bunch of things floating in soup. Another recent post by Sarah M. investigates a piece currently on view in the modern wing, Shade by London-based Dutch designer Simon Heijdens, taking a look at how the work was installed and the possible meaning behind the work. If a "little peek behind the scenes" means the opportunity to hear people talking about art in an accessible and straightforward fashion, then ARTicle certainly achieves its stated goal.

  6. Transformation of Eutypa dieback and esca disease pathogen toxins by antagonistic fungal strains reveals a second detoxification pathway not present in Vitis vinifera.

    PubMed

    Christen, Danilo; Tharin, Manuel; Perrin-Cherioux, Sandrine; Abou-Mansour, Eliane; Tabacchi, Raphaël; Défago, Geneviève

    2005-09-01

    Eutypine, 4-hydroxybenzaldehyde, and 3-phenyllactic acid are some of the phytotoxins produced by the pathogens causing Eutypa dieback and esca disease, two trunk diseases of grapevine (Vitis vinifera). Known biocontrol agents such as Fusarium lateritium and Trichoderma sp. were screened for their ability to consume these toxins. Transformation time courses were performed, and an high-performance liquid chromatography-based method was developed to analyze toxin metabolism and to identify and quantify the converted products. The results show that the aldehyde function of eutypine was reduced to eutypinol, as by V. vinifera cv. Merlot, the cultivar tolerant to Eutypa dieback. We revealed a supplementary detoxification pathway, not known in Merlot, where the aldehyde function was oxidized to eutypinic acid. Moreover, some strains tested could further metabolize the transformation products. Every strain tested could transform 4-hydroxybenzaldehyde to the corresponding alcohol and acid, and these intermediates disappeared totally at the end of the time courses. When biological assays on cells of V. vinifera cv. Chasselas were carried out, the transformation products exhibited a lower toxicity than the toxins. The possibility of selecting new biocontrol agents against trunk diseases of grapevine based on microbial detoxification is discussed. PMID:16131109

  7. Atoms in an amplitude-modulated standing wave -dynamics and pathways to quantum chaos This article has been downloaded from IOPscience. Please scroll down to see the full text article.

    E-print Network

    Queensland, University of

    Atoms in an amplitude-modulated standing wave - dynamics and pathways to quantum chaos This article­667. Printed in the UK PII: S1464-4266(00)11627-1 Atoms in an amplitude-modulated standing wave to an amplitude-modulated far-detuned standing wave of light to form a quantum-driven pendulum. Here we discuss

  8. The non-pathogenic mycobacteria M. smegmatis and M. fortuitum induce rapid host cell apoptosis via a caspase-3 and TNF dependent pathway

    Microsoft Academic Search

    Amro Bohsali; Hana Abdalla; Kamalakannan Velmurugan; Volker Briken

    2010-01-01

    BACKGROUND: The HIV pandemic raised the potential for facultative-pathogenic mycobacterial species like, Mycobacterium kansasii, to cause disseminating disease in humans with immune deficiencies. In contrast, non-pathogenic mycobacterial species, like M. smegmatis, are not known to cause disseminating disease even in immunocompromised individuals. We hypothesized that this difference in phenotype could be explained by the strong induction of an innate immune

  9. A Ligand-Receptor Mechanism in Plant-Pathogen Recognition

    NSDL National Science Digital Library

    Chris Lamb (Salk Institute for Biological Studies; Plant Biology Laboratory)

    1996-12-20

    Access to the article is free, however registration and sign-in are required. Two reports in this issue (p. 2060 and p. 2063) illustrate the molecular mechanism underlying the specificity of plant pathogens for certain plant species. In his Perspective, Lamb explains what these results teach us about signal transduction pathways in plants and how they provide a new tool for engineering crop plants.

  10. The bacterial lipopeptide iturins induce Verticillium dahliae cell death by affecting fungal signalling pathways and mediate plant defence responses involved in pathogen-associated molecular pattern-triggered immunity.

    PubMed

    Han, Qin; Wu, Fengli; Wang, Xiaonan; Qi, Hong; Shi, Liang; Ren, Ang; Liu, Qinghai; Zhao, Mingwen; Tang, Canming

    2015-04-01

    Verticillium wilt in cotton caused by Verticillium dahliae is one of the most serious plant diseases worldwide. Because no known fungicides or cotton cultivars provide sufficient protection against this pathogen, V.?dahliae causes major crop yield losses. Here, an isolated cotton endophytic bacterium, designated Bacillus amyloliquefaciens 41B-1, exhibited greater than 50% biocontrol efficacy against V.?dahliae in cotton plants under greenhouse conditions. Through high-performance liquid chromatography and mass analysis of the filtrate, we found that the antifungal compounds present in the strain 41B-1 culture filtrate were a series of isoforms of iturins. The purified iturins suppressed V.?dahliae microsclerotial germination in the absence or presence of cotton. Treatment with the iturins induced reactive oxygen species bursts, Hog1 mitogen-activated protein kinase (MAPK) activation and defects in cell wall integrity. The oxidative stress response and high-osmolarity glycerol pathway contribute to iturins resistance in V.?dahliae. In contrast, the Slt2 MAPK pathway may be involved in iturins sensitivity in this fungus. In addition to antagonism, iturins could induce plant defence responses as activators and mediate pathogen-associated molecular pattern-triggered immunity. These findings suggest that iturins may affect fungal signalling pathways and mediate plant defence responses against V.?dahliae. PMID:24934960

  11. Placeholder record for supplementary data for forthcoming journal article - "Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes/pathways linked to subsequent type 2 diabetes risk"

    E-print Network

    Quilter, Claire

    2014-06-19

    Placeholder for journal article Claire Quilter “Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes/pathways linked to subsequent type 2 diabetes...

  12. Antibiotic targeting of the bacterial secretory pathway.

    PubMed

    Rao C V, Smitha; De Waelheyns, Evelien; Economou, Anastassios; Anné, Jozef

    2014-08-01

    Finding new, effective antibiotics is a challenging research area driven by novel approaches required to tackle unconventional targets. In this review we focus on the bacterial protein secretion pathway as a target for eliminating or disarming pathogens. We discuss the latest developments in targeting the Sec-pathway for novel antibiotics focusing on two key components: SecA, the ATP-driven motor protein responsible for driving preproteins across the cytoplasmic membrane and the Type I signal peptidase that is responsible for the removal of the signal peptide allowing the release of the mature protein from the membrane. We take a bird's-eye view of other potential targets in the Sec-pathway as well as other Sec-dependent or Sec-independent protein secretion pathways as targets for the development of novel antibiotics. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. PMID:24534745

  13. Signaling During Pathogen Infection

    NSDL National Science Digital Library

    Sylvia Munter (University of Heidelberg Medical School; Department of Parasitology REV)

    2006-05-16

    Pathogens infect almost every living organism. In animals, including humans, the diversity of pathogens ranges from viruses, bacteria, and unicellular parasites to complex fungi, worms, and arthropods. Because pathogens have coevolved with their hosts and have sometimes been coopted as symbionts or commensals, each pathogen/host pair represents a striking success story of survival that reflects the biological complexity of both parties. All invading microorganisms face similar problems, such as gaining access to their host, achieving successful replication, and spreading to a similar or different host. It is therefore not surprising that many different pathogens target similar organs, cell types, and even molecules to achieve their goals. However, no two microbial parasites appear to be completely alike. Although they often target similar signaling networks, they do so in subtly different ways to achieve the desired outcome. This review has eight figures, three movies, and 139 citations and emphasizes two well-established signaling pathways that are often activated during the interaction of different pathogens with their host cells. It illustrates a small part of how the dissection of host/pathogen interactions can reveal, on a molecular scale, a nature shaped by evolutionary forces that can rival the great descriptions of our macroscopic world.

  14. The Endless Race Between Plant and Pathogen

    NSDL National Science Digital Library

    Pamela Hines (AAAS; )

    2001-06-22

    This article introduces a special issue on plant pathology, including new insights into the evolutionary forces driving plant-pathogen interactions, as well as the practical outcomes in terms of pathogen management.

  15. doi:10.1155/2011/971968 Review Article Parasite Mitogen-Activated Protein Kinases as Drug Discovery Targets to Treat Human Protozoan Pathogens

    E-print Network

    License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Protozoan pathogens are a highly diverse group of unicellular organisms, several of which are significant human pathogens. One group of protozoan pathogens includes obligate intracellular parasites such as agents of malaria, leishmaniasis, babesiosis, and toxoplasmosis. The other group includes extracellular pathogens such as agents of giardiasis and amebiasis. An unfortunate unifying theme for most human protozoan pathogens is that highly effective treatments for them are generally lacking. We will review targeting protozoan mitogen-activated protein kinases (MAPKs) as a novel drug discovery approach towards developing better therapies, focusing on Plasmodia, Leishmania,andToxoplasma, about which the most is known. 1. General Properties of MAPKs Virtually all eukaryotic organisms possess MAPKs, signal transduction molecules that regulate cell functions such as tissue morphogenesis, cytoskeletal rearrangements, proliferation, differentiation, survival, immune responses, and adaptation/stress-response [1–3]. Encephalitozoon cuniculi is the only example to date of a eukaryote apparently lacking

  16. REVIEW ARTICLE The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson’s disease

    E-print Network

    Tianhong Pan; Seiji Kondo; Weidong Le

    The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of a-synuclein and the increase of intracellular concentrations of non-mutant a-synuclein have been associated with Parkinson’s disease phenotype. The demonstration that a-synuclein is degraded by both proteasome and autophagy indicates a possible linkagebetweenthedysfunctionoftheUPSorALPandtheoccurrenceofthisdisorder.Thefactthatmutant a-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson’s disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.

  17. RESEARCH ARTICLE Open Access Meta-analysis of Chicken Salmonella infection

    E-print Network

    RESEARCH ARTICLE Open Access Meta-analysis of Chicken ­ Salmonella infection experiments Marinus FW. Chickens lines differ in susceptibility for Salmonella and can harbor Salmonella pathogens without showing and pathways are reported to be involved in the chicken host response to Salmonella infection. The objective

  18. Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

    PubMed Central

    Willis, Lisa M.; Stupak, Jacek; Richards, Michele R.; Lowary, Todd L.; Li, Jianjun; Whitfield, Chris

    2013-01-01

    Bacterial capsules are surface layers made of long-chain polysaccharides. They are anchored to the outer membrane of many Gram-negative bacteria, including pathogens such as Escherichia coli, Neisseria meningitidis, Haemophilus influenzae, and Pasteurella multocida. Capsules protect pathogens from host defenses including complement-mediated killing and phagocytosis and therefore represent a major virulence factor. Capsular polysaccharides are synthesized by enzymes located in the inner (cytoplasmic) membrane and are then translocated to the cell surface. Whereas the enzymes that synthesize the polysaccharides have been studied in detail, the structure and biosynthesis of the anchoring elements have not been definitively resolved. Here we determine the structure of the glycolipid attached to the reducing terminus of the polysialic acid capsular polysaccharides from E. coli K1 and N. meningitidis group B and the heparosan-like capsular polysaccharide from E. coli K5. All possess the same unique glycolipid terminus consisting of a lyso-phosphatidylglycerol moiety with a ?-linked poly-(3-deoxy-d-manno-oct-2-ulosonic acid) (poly-Kdo) linker attached to the reducing terminus of the capsular polysaccharide. PMID:23610430

  19. The plant pathogen Streptomyces scabies 87-22 has a functional pyochelin biosynthetic pathway that is regulated by TetR- and AfsR-family proteins.

    PubMed

    Seipke, Ryan F; Song, Lijiang; Bicz, Joanna; Laskaris, Paris; Yaxley, Alice M; Challis, Gregory L; Loria, Rosemary

    2011-09-01

    Siderophores are high-affinity iron-chelating compounds produced by bacteria for iron uptake that can act as important virulence determinants for both plant and animal pathogens. Genome sequencing of the plant pathogen Streptomyces scabies 87-22 revealed the presence of a putative pyochelin biosynthetic gene cluster (PBGC). Liquid chromatography (LC)-MS analyses of culture supernatants of S. scabies mutants, in which expression of the cluster is upregulated and which lack a key biosynthetic gene from the cluster, indicated that pyochelin is a product of the PBGC. LC-MS comparisons with authentic standards on a homochiral stationary phase confirmed that pyochelin and not enantio-pyochelin (ent-pyochelin) is produced by S. scabies. Transcription of the S. scabies PBGC occurs via ~19 kb and ~3 kb operons and transcription of the ~19 kb operon is regulated by TetR- and AfsR-family proteins encoded by the cluster. This is the first report, to our knowledge, of pyochelin production by a Gram-positive bacterium; interestingly regulation of pyochelin production is distinct from characterized PBGCs in Gram-negative bacteria. Though pyochelin-mediated iron acquisition by Pseudomonas aeruginosa is important for virulence, in planta bioassays failed to demonstrate that pyochelin production by S. scabies is required for development of disease symptoms on excised potato tuber tissue or radish seedlings. PMID:21757492

  20. Rhamnolipids Elicit Defense Responses and Induce Disease Resistance against Biotrophic, Hemibiotrophic, and Necrotrophic Pathogens That Require Different Signaling Pathways in Arabidopsis and Highlight a Central Role for Salicylic Acid1[C][W][OA

    PubMed Central

    Sanchez, Lisa; Courteaux, Barbara; Hubert, Jane; Kauffmann, Serge; Renault, Jean-Hugues; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan

    2012-01-01

    Plant resistance to phytopathogenic microorganisms mainly relies on the activation of an innate immune response usually launched after recognition by the plant cells of microbe-associated molecular patterns. The plant hormones, salicylic acid (SA), jasmonic acid, and ethylene have emerged as key players in the signaling networks involved in plant immunity. Rhamnolipids (RLs) are glycolipids produced by bacteria and are involved in surface motility and biofilm development. Here we report that RLs trigger an immune response in Arabidopsis (Arabidopsis thaliana) characterized by signaling molecules accumulation and defense gene activation. This immune response participates to resistance against the hemibiotrophic bacterium Pseudomonas syringae pv tomato, the biotrophic oomycete Hyaloperonospora arabidopsidis, and the necrotrophic fungus Botrytis cinerea. We show that RL-mediated resistance involves different signaling pathways that depend on the type of pathogen. Ethylene is involved in RL-induced resistance to H. arabidopsidis and to P. syringae pv tomato whereas jasmonic acid is essential for the resistance to B. cinerea. SA participates to the restriction of all pathogens. We also show evidence that SA-dependent plant defenses are potentiated by RLs following challenge by B. cinerea or P. syringae pv tomato. These results highlight a central role for SA in RL-mediated resistance. In addition to the activation of plant defense responses, antimicrobial properties of RLs are thought to participate in the protection against the fungus and the oomycete. Our data highlight the intricate mechanisms involved in plant protection triggered by a new type of molecule that can be perceived by plant cells and that can also act directly onto pathogens. PMID:22968829

  1. The CRE1 cytokinin pathway is differentially recruited depending on Medicago truncatula root environments and negatively regulates resistance to a pathogen.

    PubMed

    Laffont, Carole; Rey, Thomas; André, Olivier; Novero, Mara; Kazmierczak, Théophile; Debellé, Frédéric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

    2015-01-01

    Cytokinins are phytohormones that regulate many developmental and environmental responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response 1) is required for the nitrogen-fixing symbiosis with rhizobia. As several cytokinin signaling genes are modulated in roots depending on different biotic and abiotic conditions, we assessed potential involvement of this pathway in various root environmental responses. Phenotyping of cre1 mutant roots infected by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt), were carried out. Detailed histological analysis and quantification of cre1 mycorrhized roots did not reveal any detrimental phenotype, suggesting that MtCRE1 does not belong to the ancestral common symbiotic pathway shared by rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged lateral roots compared to wild-type plants, a phenotype which was also observed under non-stressed conditions. In response to A. euteiches, cre1 mutants showed reduced disease symptoms and an increased plant survival rate, correlated to an enhanced formation of lateral roots, a feature previously linked to Aphanomyces resistance. Overall, we showed that the cytokinin CRE1 pathway is not only required for symbiotic nodule organogenesis but also affects both root development and resistance to abiotic and biotic environmental stresses. PMID:25562779

  2. The CRE1 Cytokinin Pathway Is Differentially Recruited Depending on Medicago truncatula Root Environments and Negatively Regulates Resistance to a Pathogen

    PubMed Central

    Laffont, Carole; Rey, Thomas; André, Olivier; Novero, Mara; Kazmierczak, Théophile; Debellé, Frédéric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

    2015-01-01

    Cytokinins are phytohormones that regulate many developmental and environmental responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response 1) is required for the nitrogen-fixing symbiosis with rhizobia. As several cytokinin signaling genes are modulated in roots depending on different biotic and abiotic conditions, we assessed potential involvement of this pathway in various root environmental responses. Phenotyping of cre1 mutant roots infected by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt), were carried out. Detailed histological analysis and quantification of cre1 mycorrhized roots did not reveal any detrimental phenotype, suggesting that MtCRE1 does not belong to the ancestral common symbiotic pathway shared by rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged lateral roots compared to wild-type plants, a phenotype which was also observed under non-stressed conditions. In response to A. euteiches, cre1 mutants showed reduced disease symptoms and an increased plant survival rate, correlated to an enhanced formation of lateral roots, a feature previously linked to Aphanomyces resistance. Overall, we showed that the cytokinin CRE1 pathway is not only required for symbiotic nodule organogenesis but also affects both root development and resistance to abiotic and biotic environmental stresses. PMID:25562779

  3. The Arabidopsis Rho of Plants GTPase AtROP6 Functions in Developmental and Pathogen Response Pathways1[C][W][OA

    PubMed Central

    Poraty-Gavra, Limor; Zimmermann, Philip; Haigis, Sabine; Bednarek, Pawe?; Hazak, Ora; Stelmakh, Oksana Rogovoy; Sadot, Einat; Schulze-Lefert, Paul; Gruissem, Wilhelm; Yalovsky, Shaul

    2013-01-01

    How plants coordinate developmental processes and environmental stress responses is a pressing question. Here, we show that Arabidopsis (Arabidopsis thaliana) Rho of Plants6 (AtROP6) integrates developmental and pathogen response signaling. AtROP6 expression is induced by auxin and detected in the root meristem, lateral root initials, and leaf hydathodes. Plants expressing a dominant negative AtROP6 (rop6DN) under the regulation of its endogenous promoter are small and have multiple inflorescence stems, twisted leaves, deformed leaf epidermis pavement cells, and differentially organized cytoskeleton. Microarray analyses of rop6DN plants revealed that major changes in gene expression are associated with constitutive salicylic acid (SA)-mediated defense responses. In agreement, their free and total SA levels resembled those of wild-type plants inoculated with a virulent powdery mildew pathogen. The constitutive SA-associated response in rop6DN was suppressed in mutant backgrounds defective in SA signaling (nonexpresser of PR genes1 [npr1]) or biosynthesis (salicylic acid induction deficient2 [sid2]). However, the rop6DN npr1 and rop6DN sid2 double mutants retained the aberrant developmental phenotypes, indicating that the constitutive SA response can be uncoupled from ROP function(s) in development. rop6DN plants exhibited enhanced preinvasive defense responses to a host-adapted virulent powdery mildew fungus but were impaired in preinvasive defenses upon inoculation with a nonadapted powdery mildew. The host-adapted powdery mildew had a reduced reproductive fitness on rop6DN plants, which was retained in mutant backgrounds defective in SA biosynthesis or signaling. Our findings indicate that both the morphological aberrations and altered sensitivity to powdery mildews of rop6DN plants result from perturbations that are independent from the SA-associated response. These perturbations uncouple SA-dependent defense signaling from disease resistance execution. PMID:23319551

  4. Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

    PubMed Central

    Aruni, A. Wilson; Zhang, Kangling; Dou, Yuetan

    2014-01-01

    Changes in periodontal status are associated with shifts in the composition of the bacterial community in the periodontal pocket. The relative abundances of several newly recognized microbial species, including Filifactor alocis, as-yet-unculturable organisms, and other fastidious organisms have raised questions on their impact on disease development. We have previously reported that the virulence attributes of F. alocis are enhanced in coculture with Porphyromonas gingivalis. We have evaluated the proteome of host cells and F. alocis during a polymicrobial infection. Coinfection of epithelial cells with F. alocis and P. gingivalis strains showed approximately 20% to 30% more proteins than a monoinfection. Unlike F. alocis ATCC 35896, the D-62D strain expressed more proteins during coculture with P. gingivalis W83 than with P. gingivalis 33277. Proteins designated microbial surface component-recognizing adhesion matrix molecules (MSCRAMMs) and cell wall anchor proteins were highly upregulated during the polymicrobial infection. Ultrastructural analysis of the epithelial cells showed formation of membrane microdomains only during coinfection. The proteome profile of epithelial cells showed proteins related to cytoskeletal organization and gene expression and epigenetic modification to be in high abundance. Modulation of proteins involved in apoptotic and cell signaling pathways was noted during coinfection. The enhanced virulence potential of F. alocis may be related to the differential expression levels of several putative virulence factors and their effects on specific host cell pathways. PMID:24866790

  5. Increased Ki?67 proliferative index and absence of P16INK4 in CIN?HPV related pathogenic pathways different from cervical squamous intraepithelial lesion

    PubMed Central

    Kuo, K?T; Chang, H?C; Hsiao, C?H; Lin, M?C

    2006-01-01

    Background/aim It is generally assumed that similar pathways are involved in human papillomavirus (HPV) induced pathogenesis of cervical squamous intraepithelial lesions (SILs) and cancers and a subset of conjunctival intraepithelial neoplasm (CIN)—that the malignancies or pre?cancerous lesions arise through HPV oncoproteins E6 and E7, which disrupt the pathways of p53 and the product of the retinoblastoma (Rb) gene and, in turn, increase the protein product of gene p16INK4 through the mechanism of positive feedback. Several cell cycle molecules are detected to test this hypothesis. Methods Nine cases of CIN and eight non?CIN cases were analysed for the expression of Ki?67, pRb, p53, and p16INK4 via immunohistochemistry. Nine cases of cervical high grade squamous intraepithelial lesion (HSIL), and 10 cases of cervical low grade squamous intraepithelial lesion (LSIL) were included for stain control of p16INK4a, and comparison of p16INK4a expression to CIN cases. A nested polymerase chain reaction and a genechip HPV typing were used to detect HPV infection and types in the CIN and non?CIN samples Results HPV positivity was demonstrated in all of the CIN lesions but in none of the non?CIN lesions. The Ki?67 proliferative index (Ki?67 PI) was statistically higher in the CIN group than the non?CIN group; however, there were no differences of expression of pRb and p53 between the two groups and no expression of p16INK4 in all cases. All nine cases of HSIL, and seven out of 10 cases of LSIL used for stain control were immunoreactive for p16INK4a. There were statistically significant differences in overexpression of p16INK4a between the CINs and SILs Conclusions The Ki?67 proliferative index may be a sensitive marker for CIN lesions and these results, with significant differences in overexpression of p16INK4a between CINs and SILs, may provide new evidence that HPV related mucosal dysplasia in different anatomical locations may lead to dissimilar molecular pathways. PMID:16540490

  6. N-Acyl-Homoserine Lactone Primes Plants for Cell Wall Reinforcement and Induces Resistance to Bacterial Pathogens via the Salicylic Acid/Oxylipin Pathway[C][W][OPEN

    PubMed Central

    Schenk, Sebastian T.; Hernández-Reyes, Casandra; Samans, Birgit; Stein, Elke; Neumann, Christina; Schikora, Marek; Reichelt, Michael; Mithöfer, Axel; Becker, Annette; Kogel, Karl-Heinz; Schikora, Adam

    2014-01-01

    The ability of plants to monitor their surroundings, for instance the perception of bacteria, is of crucial importance. The perception of microorganism-derived molecules and their effector proteins is the best understood of these monitoring processes. In addition, plants perceive bacterial quorum sensing (QS) molecules used for cell-to-cell communication between bacteria. Here, we propose a mechanism for how N-acyl-homoserine lactones (AHLs), a group of QS molecules, influence host defense and fortify resistance in Arabidopsis thaliana against bacterial pathogens. N-3-oxo-tetradecanoyl-l-homoserine lactone (oxo-C14-HSL) primed plants for enhanced callose deposition, accumulation of phenolic compounds, and lignification of cell walls. Moreover, increased levels of oxylipins and salicylic acid favored closure of stomata in response to Pseudomonas syringae infection. The AHL-induced resistance seems to differ from the systemic acquired and the induced systemic resistances, providing new insight into inter-kingdom communication. Consistent with the observation that short-chain AHLs, unlike oxo-C14-HSL, promote plant growth, treatments with C6-HSL, oxo-C10-HSL, or oxo-C14-HSL resulted in different transcriptional profiles in Arabidopsis. Understanding the priming induced by bacterial QS molecules augments our knowledge of plant reactions to bacteria and suggests strategies for using beneficial bacteria in plant protection. PMID:24963057

  7. Non-nucleoside Inhibitors of BasE, An Adenylating Enzyme in the Siderophore Biosynthetic Pathway of the Opportunistic Pathogen Acinetobacter baumannii

    PubMed Central

    Neres, João; Engelhart, Curtis A.; Drake, Eric J.; Wilson, Daniel J.; Fu, Peng; Boshoff, Helena I.; Barry, Clifton E.; Gulick, Andrew M.; Aldrich, Courtney C.

    2013-01-01

    Siderophores are small-molecule iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions, such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening of against BasE, which is involved in siderophore biosynthesis in A. baumannii and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochemical, and microbiological evaluation of a systematic series of analogues of the HTS hit 15. Analogue 67 is the most potent analogue with a KD of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveal they bind in a unique orientation in the active site occupying all three substrate binding sites, and thus can be considered multisubstrate inhibitors. These results provide a foundation for future studies aimed at both increasing enzyme potency and antibacterial activity. PMID:23437866

  8. A Luman/CREB3–ADP-ribosylation factor 4 (ARF4) signaling pathway mediates the response to Golgi stress and susceptibility to pathogens

    PubMed Central

    Reiling, Jan H.; Olive, Andrew J.; Sanyal, Sumana; Carette, Jan E.; Brummelkamp, Thijn R.; Ploegh, Hidde L.; Starnbach, Michael N.; Sabatini, David M.

    2014-01-01

    SUMMARY Treatment of cells with Brefeldin A (BFA) blocks secretory vesicle transport and causes a collapse of the Golgi apparatus. To gain more insight into the cellular mechanisms mediating BFA toxicity, we conducted a genome-wide haploid genetic screen that led to the identification of the small G protein ADP-ribosylation factor 4 (ARF4). ARF4 depletion preserves viability, Golgi integrity and cargo trafficking in the presence of BFA, and these effects depend on the guanine nucleotide exchange factor GBF1 and other ARF isoforms including ARF1 and ARF5. ARF4 knockdown cells show increased resistance to several human pathogens including Chlamydia trachomatis and Shigella flexneri. Furthermore, ARF4 expression is induced when cells are exposed to several Golgi-disturbing agents and requires the CREB3/Luman transcription factor whose downregulation mimics ARF4 loss. Thus, we have uncovered a CREB3–ARF4 signaling cascade that may be part of a Golgi stress response set in motion by stimuli compromising Golgi capacity. PMID:24185178

  9. Activation of Type I and III Interferon Signalling Pathways Occurs in Lung Epithelial Cells Infected with Low Pathogenic Avian Influenza Viruses

    PubMed Central

    Sutejo, Richard; Yeo, Dawn S.; Myaing, Myint Zu; Hui, Chen; Xia, Jiajia; Ko, Debbie; Cheung, Peter C. F.; Tan, Boon-Huan; Sugrue, Richard J.

    2012-01-01

    The host response to the low pathogenic avian influenza (LPAI) H5N2, H5N3 and H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK cells, while the H9N2 virus replicated least efficiently in these cell types. However, all LPAI viruses exhibited similar and higher replication efficiencies in CEF cells. A comparison of the host responses of these viruses and the H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549 cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I and Type III interferon (IFN) expression, sustained STAT1 activation from between 3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG) expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN virus showed only small increases in Type III IFN signalling, low levels of ISG expression, and down-regulated expression of the IFN type I receptor. JNK activation and increased expression of the pro-apoptotic XAF1 protein was observed in A549 cells infected with all viruses except the H1N1/WSN virus, while MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5 virus subtypes. No IFN expression and low ISG expression levels were generally observed in CEF cells infected with either AIV, while increased IFN and ISG expression was observed in response to the H1N1/WSN infection. These data suggest differences in the replication characteristics and antivirus signalling responses both among the different LPAI viruses, and between these viruses and the H1N1 viruses examined. These virus-specific differences in host cell signalling highlight the importance of examining the host response to avian influenza viruses that have not been extensively adapted to mammalian tissue culture. PMID:22470468

  10. Review Article Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

    E-print Network

    Donavon Hiss

    Copyright © 2012 Donavon Hiss. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in the BRCA1 or BRCA2 genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales. 1.

  11. First Encounter: How Pathogens Compromise Epithelial Transport

    NSDL National Science Digital Library

    Dr. Karl Kunzelmann (Universität Regensburg)

    2004-10-01

    Pathogenic organisms trigger numerous signaling pathways that ultimately lead to drastic changes in physiological functions. Apart from altering structure and function of the epithelial tight junction barrier and activating inflammatory cascades, they induce changes in fluid and electrolyte transport. Pathogens do so by activating or by inhibiting ion channels and transporters, and the result might be to their benefit or to their disadvantage

  12. Detection of enteric pathogens by the nodosome

    PubMed Central

    Keestra, A. Marijke; Bäumler, Andreas J.

    2014-01-01

    Nucleotide-binding oligomerization domain protein (NOD)1 and NOD2 participate in signaling pathways that detect pathogen-induced processes, such as the presence of peptidoglycan fragments in the host cell cytosol, as danger signals. Recent work suggests that peptidoglycan fragments activate NOD1 indirectly, through activation of the small Rho GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1). Excessive activation of small Rho GTPases by virulence factors of enteric pathogens also triggers the NOD1 signaling pathway. Many enteric pathogens use virulence factors that alter the activation state of small Rho GTPases, thereby manipulating the host cell cytoskeleton of intestinal epithelial cells to promote bacterial attachment or entry. These data suggest that the NOD1 signaling pathway in intestinal epithelial cells provides an important sentinel function for detecting ‘breaking and entering’ by enteric pathogens. PMID:24268520

  13. 3791Research Article Introduction

    E-print Network

    Jenny, Andreas

    pathways, including Hedgehog, Wnt, PDGF and FGF (Badano et al., 2005; Bisgrove and Yost, 20063791Research Article Introduction Wnt signaling pathways play crucial roles in cell proliferation in diverse organisms and distinct tissues remains to be clarified. The canonical Wnt pathway is known

  14. Conserved Pro-Glu (PE) and Pro-Pro-Glu (PPE) Protein Domains Target LipY Lipases of Pathogenic Mycobacteria to the Cell Surface via the ESX-5 Pathway*

    PubMed Central

    Daleke, Maria H.; Cascioferro, Alessandro; de Punder, Karin; Ummels, Roy; Abdallah, Abdallah M.; van der Wel, Nicole; Peters, Peter J.; Luirink, Joen; Manganelli, Riccardo; Bitter, Wilbert

    2011-01-01

    The type VII secretion system ESX-5 is a major pathway for export of PE and PPE proteins in pathogenic mycobacteria. These mycobacteria-specific protein families are characterized by conserved N-terminal domains of 100 and 180 amino acids, which contain the proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) motifs after which they are named. Here we investigated secretion of the triacylglycerol lipase LipY, which in fast-growing mycobacteria contains a signal sequence, but in slow-growing species appears to have replaced the signal peptide with a PE or PPE domain. Selected LipY homologues were expressed in wild-type Mycobacterium marinum and its corresponding ESX-5 mutant, and localization of the proteins was investigated by immunoblotting and electron microscopy. Our study shows that Mycobacterium tuberculosis PE-LipY (LipYtub) and M. marinum PPE-LipY (LipYmar) are both secreted to the bacterial surface in an ESX-5-dependent fashion. After transport, the PE/PPE domains are removed by proteolytic cleavage. In contrast, Mycobacterium gilvum LipY, which has a signal sequence, is not transported to the cell surface. Furthermore, we show that LipYtub and LipYmar require their respective PE and PPE domains for ESX-5-dependent secretion. The role of the PE domain in ESX-5 secretion was confirmed in a whole cell lipase assay, in which wild-type bacteria expressing full-length LipYtub, but not LipYtub lacking its PE domain, were shown to hydrolyze extracellular lipids. In conclusion, both PE and PPE domains contain a signal required for secretion of LipY by the ESX-5 system, and these domains are proteolytically removed upon translocation. PMID:21471225

  15. A View of the IMD Pathway from the RHIM

    Microsoft Academic Search

    Kamna Aggarwal

    2010-01-01

    Innate immunity is the first line of defense against invading pathogens. It functions to eliminate pathogens and also to control infections. The innate immune response is also important for the development of pathogen-specific adaptive immune responses. As a result, the study of innate immune signaling pathways is crucial for understanding the interactions between host and pathogen. Unlike mammals, insects lack

  16. Original article Physiology, pathogenicity and immunogenicity

    E-print Network

    Boyer, Edmond

    of Salmonella Gallinarum as vaccine candidates for fowl typhoid Kiku MATSUDA 1 , Atul A. CHAUDHARI 1 , Sam Woong (Received 8 January 2010; accepted 20 May 2010) Abstract ­ To construct a novel live vaccine candidate for fowl typhoid (FT) caused by Salmonella Gallinarum (SG), the lon and cpxR genes that are related to host

  17. BIOSYNTHETIC PATHWAYS: Biosynthesis Meets Bioinformatics

    NSDL National Science Digital Library

    David E. Cane (Brown University; Department of Chemistry)

    2000-02-04

    Access to the article is free, however registration and sign-in are required. In his Perspective, Cane discusses the increasing importance of the study of biosynthetic pathways in the discovery of biochemical reactions and pathways. Two recent papers (Rohdich et al. and Khaleeli et al.) highlight the increasing role of molecular biology and genomics in the study of biosynthetic pathways.

  18. Protein signaling via type III secretion pathways in phytopathogenic bacteria

    E-print Network

    Mudgettt, Mary Beth

    109 Protein signaling via type III secretion pathways in phytopathogenic bacteria Mary Beth Mudgett secretion pathway has revealed new mechanisms by which phytopathogenic bacteria infect plants are continually exposed to a number of potentially pathogenic bacteria. Phytopathogenic bacteria, in general

  19. [Advance on the pathogenicity and immunological application of bacterial flagella--a review].

    PubMed

    Guo, Zhiyan; Zhou, Mingxu; Duan, Qiangde; Zhu, Guoqiang

    2014-03-01

    Being a surface structure of bacteria, flagella have been thought to simply act as the locomotive organelles for a long time. In recent years, as increasing information gathered from studies on the pathogenicity of flagella, we found flagella could contribute to invasion and adhesion to the host cells, playing an important role in the biofilm formation and being correlated with bacterial virulence secretion system. Binding of flagellin and toll-like receptor 5 may stimulate signaling pathway, resulting in the pro-inflammatory response. Meanwhile, flagella act as a new immune adjuvant as well, because of their good immunity character. This article summarizes the current knowledge of bacterial flagella, including their structure, contribution to the pathogenicity of the bacteria, and their potential application in immunity. PMID:24984516

  20. Cell Host & Microbe Short Article

    E-print Network

    Nizet, Victor

    #12;Cell Host & Microbe Short Article The Globally Disseminated M1T1 Clone of Group A Streptococcus the intracellular bacterial pathogen Group A Streptococcus (GAS). However, the GAS strains examined to date belong A Streptococcus (GAS) is an obligate human pathogen and the fourth most common bacterial cause of human mortality

  1. MAIT cells and pathogen defense.

    PubMed

    Cowley, Siobhán C

    2014-12-01

    Mucosa-associated invariant T (MAIT) cells are a unique population of innate T cells that are abundant in humans. These cells possess an evolutionarily conserved invariant T cell receptor ? chain restricted by the nonpolymorphic class Ib major histocompatibility (MHC) molecule, MHC class I-related protein (MR1). The recent discovery that MAIT cells are activated by MR1-bound riboflavin metabolite derivatives distinguishes MAIT cells from all other ?? T cells in the immune system. Since mammals lack the capacity to synthesize riboflavin, intermediates from the riboflavin biosynthetic pathway are distinct microbial molecular patterns that provide a unique signal to the immune system. Multiple lines of evidence suggest that MAIT cells, which produce important cytokines such as IFN-?, TNF, and IL-17A, have the potential to influence immune responses to a broad range of pathogens. Here we will discuss our current understanding of MAIT cell biology and their role in pathogen defense. PMID:25164578

  2. Email Article Print Article

    E-print Network

    Yan, Zhen

    of Good Housekeeping magazine. The article interviews her on some of the benefits of stress, and notes#12;#12;#12;#12;#12;Email Article Print Article Subscribe to News Like This ShareThis Contact John conducted by Zhen Yan, professor of physiology and biophysics, is featured in an article in the May issue

  3. Viroid Pathogenicity: One Process, Many Faces

    PubMed Central

    Owens, Robert A.; Hammond, Rosemarie W.

    2009-01-01

    Despite the non-coding nature of their small RNA genomes, the visible symptoms of viroid infection resemble those associated with many plant virus diseases. Recent evidence indicates that viroid-derived small RNAs acting through host RNA silencing pathways play a key role in viroid pathogenicity. Host responses to viroid infection are complex, involving signaling cascades containing host-encoded protein kinases and crosstalk between hormonal and defense-signaling pathways. Studies of viroid-host interaction in the context of entire biochemical or developmental pathways are just beginning, and many working hypotheses have yet to be critically tested. PMID:21994551

  4. The cuticle and plant defense to pathogens

    PubMed Central

    Serrano, Mario; Coluccia, Fania; Torres, Martha; L’Haridon, Floriane; Métraux, Jean-Pierre

    2014-01-01

    The cuticle provides a physical barrier against water loss and protects against irradiation, xenobiotics, and pathogens. Components of the cuticle are perceived by invading fungi and activate developmental processes during pathogenesis. In addition, cuticle alterations of various types induce a syndrome of reactions that often results in resistance to necrotrophs. This article reviews the current knowledge on the role of the cuticle in relation to the perception of pathogens and activation of defenses. PMID:24982666

  5. Pathogens Hijack the Epigenome

    PubMed Central

    Silmon de Monerri, Natalie C.; Kim, Kami

    2015-01-01

    Pathogens have evolved strategies to promote their survival by dramatically modifying the transcriptional profile and protein content of the host cells they infect. Modifications of the host transcriptome and proteome are mediated by pathogen-encoded effector molecules that modulate host cells through a variety of different mechanisms. Recent studies highlight the importance of the host chromatin and other epigenetic regulators as targets of pathogens. Host gene regulatory mechanisms may be targeted through cytoplasmic signaling, directly by pathogen effector proteins, and possibly by pathogen RNA. Although many of these changes are short-lived and persist only during the course of infection, several studies indicate that pathogens are able to induce long-term, heritable changes that are essential to pathogenesis of infectious diseases and persistence of pathogens within their hosts. In this review, we discuss how pathogens modulate the epigenome of host cells, a new and flourishing avenue of host-pathogen interaction studies. PMID:24525150

  6. Molecular Pathways: The Hedgehog Signaling Pathway in Cancer

    PubMed Central

    McMillan, Ross; Matsui, William

    2012-01-01

    The Hedgehog (Hh) signaling pathway regulates embryonic development and may be aberrantly activated in a wide variety of human cancers. Efforts to target pathogenic Hh signaling have steadily progressed from the laboratory to the clinic, and the recent approval of the Hh pathway inhibitor vismodegib for patients with advanced basal cell carcinoma (BCC) represents an important milestone. On the other hand, Hh pathway antagonists have failed to demonstrate significant clinical activity in other solid tumors. The reasons for these negative results are not precisely understood, but it is possible that the impact of Hh pathway inhibition has not been adequately measured by the clinical endpoints used thus far or that aberrancies in Hh signal transduction limit the activity of currently available pathway antagonists. Further basic and correlative studies to better understand Hh signaling in human tumors and validate putative anti-tumor mechanisms in the clinical setting may ultimately improve the success of Hh pathway inhibition to other tumor types. PMID:22718857

  7. Fungal Pathogens: Survival and Replication within Macrophages.

    PubMed

    Gilbert, Andrew S; Wheeler, Robert T; May, Robin C

    2014-11-10

    The innate immune system is a critical line of defense against pathogenic fungi. Macrophages act at an early stage of infection, detecting and phagocytizing infectious propagules. To avoid killing at this stage, fungal pathogens use diverse strategies ranging from evasion of uptake to intracellular parasitism. This article will discuss five of the most important human fungal pathogens (Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Coccidiodes immitis, and Histoplasma capsulatum) and consider the strategies and virulence factors adopted by each to survive and replicate within macrophages. PMID:25384769

  8. Modulation of pathogen recognition by autophagy.

    PubMed

    Oh, Ji Eun; Lee, Heung Kyu

    2012-01-01

    Autophagy is an ancient biological process for maintaining cellular homeostasis by degradation of long-lived cytosolic proteins and organelles. Recent studies demonstrated that autophagy is availed by immune cells to regulate innate immunity. On the one hand, cells exert direct effector function by degrading intracellular pathogens; on the other hand, autophagy modulates pathogen recognition and downstream signaling for innate immune responses. Pathogen recognition via pattern recognition receptors induces autophagy. The function of phagocytic cells is enhanced by recruitment of autophagy-related proteins. Moreover, autophagy acts as a delivery system for viral replication complexes to migrate to the endosomal compartments where virus sensing occurs. In another case, key molecules of the autophagic pathway have been found to negatively regulate immune signaling, thus preventing aberrant activation of cytokine production and consequent immune responses. In this review, we focus on the recent advances in the role of autophagy in pathogen recognition and modulation of innate immune responses. PMID:22566926

  9. PATHOGENS: VIEWS OF EPA'S PATHOGEN EQUIVALENCY COMMITTEE

    EPA Science Inventory

    This presentation reviews the pathogenic microorganisms that may be found in municipal sewage sludge and the commonly employed Class A and B processes for controlling pathogens. It notes how extensively they are used and discusses issues and concerns with their application. Pre...

  10. RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic lateral sclerosis

    PubMed Central

    Chan, Ho Yin Edwin

    2014-01-01

    Gene transcription produces a wide variety of ribonucleic acid (RNA) species in eukaryotes. Individual types of RNA, such as messenger, structural and regulatory RNA, are known to play distinct roles in the cell. Recently, researchers have identified a large number of RNA-mediated toxicity pathways that play significant pathogenic roles in numerous human disorders. In this article, we describe various common RNA toxicity pathways, namely epigenetic gene silencing, nucleolar stress, nucleocytoplasmic transport, bi-directional gene transcription, repeat-associated non-ATG translation, RNA foci formation and cellular protein sequestration. We emphasize RNA toxicity mechanisms that involve nucleotide repeat expansion, such as those related to polyglutamine (polyQ) disorders and frontotemporal lobar degeneration-amyotrophic lateral sclerosis. PMID:25565965

  11. Modulation of NF-?B signalling by microbial pathogens

    PubMed Central

    Rahman, Masmudur M.; McFadden, Grant

    2013-01-01

    The nuclear factor-?B (NF-?B) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-?B proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-?B signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF-?B signalling circuitry to favour the continued survival of the pathogen. PMID:21383764

  12. Metagenomes of Microbial Communities in Arsenic- and Pathogen-Contaminated Well and Surface Water from Bangladesh

    PubMed Central

    Layton, Alice C.; Chauhan, Archana; Williams, Daniel E.; Mailloux, Brian; Knappett, Peter S. K.; Ferguson, Andrew S.; McKay, Larry D.; Alam, M. Jahangir; Matin Ahmed, Kazi; van Geen, Alexander

    2014-01-01

    The contamination of drinking water from both arsenic and microbial pathogens occurs in Bangladesh. A general metagenomic survey of well water and surface water provided information on the types of pathogens present and may help elucidate arsenic metabolic pathways and potential assay targets for monitoring surface-to-ground water pathogen transport. PMID:25414497

  13. Metagenomes of microbial communities in arsenic- and pathogen-contaminated well and surface water from bangladesh.

    PubMed

    Layton, Alice C; Chauhan, Archana; Williams, Daniel E; Mailloux, Brian; Knappett, Peter S K; Ferguson, Andrew S; McKay, Larry D; Alam, M Jahangir; Matin Ahmed, Kazi; van Geen, Alexander; Sayler, Gary S

    2014-01-01

    The contamination of drinking water from both arsenic and microbial pathogens occurs in Bangladesh. A general metagenomic survey of well water and surface water provided information on the types of pathogens present and may help elucidate arsenic metabolic pathways and potential assay targets for monitoring surface-to-ground water pathogen transport. PMID:25414497

  14. Taxonomy of bacterial fish pathogens

    PubMed Central

    2011-01-01

    Bacterial taxonomy has progressed from reliance on highly artificial culture-dependent techniques involving the study of phenotype (including morphological, biochemical and physiological data) to the modern applications of molecular biology, most recently 16S rRNA gene sequencing, which gives an insight into evolutionary pathways (= phylogenetics). The latter is applicable to culture-independent approaches, and has led directly to the recognition of new uncultured bacterial groups, i.e. "Candidatus", which have been associated as the cause of some fish diseases, including rainbow trout summer enteritic syndrome. One immediate benefit is that 16S rRNA gene sequencing has led to increased confidence in the accuracy of names allocated to bacterial pathogens. This is in marked contrast to the previous dominance of phenotyping, and identifications, which have been subsequently challenged in the light of 16S rRNA gene sequencing. To date, there has been some fluidity over the names of bacterial fish pathogens, with some, for example Vibrio anguillarum, being divided into two separate entities (V. anguillarum and V. ordalii). Others have been combined, for example V. carchariae, V. harveyi and V. trachuri as V. harveyi. Confusion may result with some organisms recognized by more than one name; V. anguillarum was reclassified as Beneckea and Listonella, with Vibrio and Listonella persisting in the scientific literature. Notwithstanding, modern methods have permitted real progress in the understanding of the taxonomic relationships of many bacterial fish pathogens. PMID:21314902

  15. CELL SIGNALING: Mitochondrial Longevity Pathways

    NSDL National Science Digital Library

    György Hajnóczky (Thomas Jefferson University; Department of Pathology, Anatomy and Cell Biology)

    2007-02-02

    Access to the article is free, however registration and sign-in are required. A cytosolic protein that translocates into the mitochondria may serve as an integration point for signaling pathways that control longevity and cell death.

  16. Coevolution of Plants and Their Pathogens in Natural Habitats

    NSDL National Science Digital Library

    Jeremy J. Burdon (Commonwealth Scientific and Industrial Research Organization (CSIRO)â??Plant Industry; )

    2009-05-08

    Access to the article is free, however registration and sign-in are required. Understanding of plant-pathogen coevolution in natural systems continues to develop as new theories at the population and species level are increasingly informed by studies unraveling the molecular basis of interactions between individual plants and their pathogens.

  17. A nutritive view on the host–pathogen interplay

    Microsoft Academic Search

    Ulrich E. Schaible; Stefan H. E. Kaufmann

    2005-01-01

    The interaction between pathogenic microbes and their host is determined by survival strategies on both sides, including competition for essential nutrients. During evolution, pathogenic microbes developed ways to access certain nutrients from the host, which, by contrast, can be exploited by the host for defence by restricting the availability of these nutrients. In this article, we review ecological aspects of

  18. Pathogenic Microorganisms in Water

    NSDL National Science Digital Library

    Melissa Lenczewski

    Pathogenic Microorganisms in Water: Traditionally, groundwater has been used without treatment because the soil acts as a filter, removing pathogenic microorganisms. Some potential sources of pathogens (or disease causing organisms) in groundwater include septic tanks, leaking sewer lines, sewage sludge, intentional groundwater recharge with sewage, irrigation with sewage, direct injection of sewage, domestic solid waste disposal (landfills) and sewage oxidation ponds. The objective of the session is to introduce hydrogeologist to the types of microorganisms, sources of pathogens, and a simple exercise that can be incorporated into a hydrogeology class.

  19. Autophagy vitalizes the pathogenicity of pathogenic fungi.

    PubMed

    Liu, Xiao-Hong; Gao, Hui-Min; Xu, Fei; Lu, Jian-Ping; Devenish, Rodney J; Lin, Fu-Cheng

    2012-10-01

    Plant pathogenic fungi utilize a series of complex infection structures, in particular the appressorium, to gain entry to and colonize plant tissue. As a consequence of the accumulation of huge quantities of glycerol in the cell the appressorium generates immense intracellular turgor pressure allowing the penetration peg of the appressorium to penetrate the leaf cuticle. Autophagic processes are ubiquitous in eukaryotic cells and facilitate the bulk degradation of macromolecules and organelles. The study of autophagic processes has been extended from the model yeast Saccharomyces cerevisiae to pathogenic fungi such as the rice blast fungus Magnaporthe oryzae. Significantly, null mutants for the expression of M. oryzae autophagy gene homologs lose their pathogenicity for infection of host plants. Clarification of the functions and network of interactions between the proteins expressed by M. oryzae autophagy genes will lead to a better understanding of the role of autophagy in fungal pathogenesis and help in the development of new strategies for disease control. PMID:22935638

  20. Emerging foodborne pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence of new foodborne pathogens is due to a number of factors. An important factor is the globalization of the food supply with the possibility of the introduction of foodborne pathogens from other countries. Animal husbandry, food production, food processing, and food distribution system...

  1. Highly Pathogenic Avian Influenza

    E-print Network

    Boyer, Edmond

    Highly Pathogenic Avian Influenza Virus (H5N1) Outbreak in Captive Wild Birds and Cats, Cambodia Tamao Wildlife Rescue Centre, Cambodia, was affected by the highly pathogenic influenza virus (H5N1). Birds from 26 species died. Influenza virus subtype H5N1 was detected in 6 of 7 species tested. Cats

  2. Emerging Escherichia Pathogen

    PubMed Central

    Permpalung, Nitipong; Sentochnik, Deborah E.

    2013-01-01

    Escherichia hermannii was first identified as a new species in 1982. It has rarely been reported as a human pathogen. We report the first case of E. hermannii as the sole pathogen in a catheter-related bloodstream infection. PMID:23740732

  3. Plant pathogen resistance

    DOEpatents

    Greenberg, Jean T; Jung, Ho Won; Tschaplinski, Timothy

    2012-11-27

    Azelaic acid or its derivatives or analogs induce a robust and a speedier defense response against pathogens in plants. Azelaic acid treatment alone does not induce many of the known defense-related genes but activates a plant's defense signaling upon pathogen exposure.

  4. BACTERIAL WATERBORNE PATHOGENS

    EPA Science Inventory

    Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

  5. Identification of veterinary pathogens by use of commercial identification systems and new trends in antimicrobial susceptibility testing of veterinary pathogens.

    PubMed Central

    Watts, J L; Yancey, R J

    1994-01-01

    Veterinary diagnostic microbiology is a unique specialty within microbiology. Although isolation and identification techniques are similar to those used for human pathogens, many veterinary pathogens require unique cultivation or identification procedures. Commercial identification systems provide rapid, accurate identification of human pathogens. However, the accuracy of these systems with veterinary pathogens varies widely depending on the bacterial species and the host animal from which it was isolated. Increased numbers of veterinary strains or species in the data bases of the various systems would improve their accuracy. Current procedures and interpretive criteria used for antimicrobial susceptibility testing of veterinary pathogens are based on guidelines used for human pathogens. The validity of these guidelines for use with veterinary pathogens has not been established. As with fastidious human pathogens, standardized methodologies and quality control isolates are needed for tests of organisms such as Actinobacillus pleuropneumoniae and Haemophilus somnus. Furthermore, interpretive criteria for veterinary antimicrobial agents based on the MIC for veterinary pathogens, the pharmacokinetics of the antimicrobial agent in the host animal, and in vivo efficacy of the antimicrobial agent are needed. This article reviews both the commercial identification systems evaluated with veterinary pathogens and current methods for performing and interpreting antimicrobial susceptibility tests with veterinary pathogens. Recommendations for future improvements in both areas are discussed. PMID:7923054

  6. Processes for managing pathogens.

    PubMed

    Godfree, Alan; Farrell, Joseph

    2005-01-01

    Wastewater contains human, animal, and plant pathogens capable of causing viral, bacterial, or parasitic infections. There are several routes whereby sewage pathogens may affect human health, including direct contact, contamination of food crops, zoonoses, and vectors. The range and numbers of pathogens in municipal wastewater vary with the level of endemic disease in the community, discharges from commercial activities, and seasonal factors. Regulations to control pathogen risk in the United States and Europe arising from land application of biosolids are based on the concept of multiple barriers to the prevention of transmission. The barriers are (i) treatment to reduce pathogen content and vector attraction, (ii) restrictions on crops grown on land to which biosolids have been applied, and (iii) minimum intervals following application and grazing or harvesting. Wastewater treatment reduces number of pathogens in the wastewater by concentrating them with the solids in the sludge. Although some treatment processes are designed specifically to inactivate pathogens, many are not, and the actual mechanisms of microbial inactivation are not fully understood for all processes. Vector attraction is reduced by stabilization (reduction of readily biodegradable material) and/or incorporation immediately following application. Concerns about health risks have renewed interest in the effects of treatment (on pathogens) and advanced treatment methods, and work performed in the United States suggests that Class A pathogen reduction can be achieved less expensively than previously thought. Effective pathogen risk management requires control to the complete chain of sludge treatment, biosolids handling and application, and post-application activities. This may be achieved by adherence to quality management systems based on hazard analysis critical control point (HACCP) principles. PMID:15647539

  7. Pathogenic Mechanisms in Centronuclear Myopathies

    PubMed Central

    Jungbluth, Heinz; Gautel, Mathias

    2014-01-01

    Centronuclear myopathies (CNMs) are a genetically heterogeneous group of inherited neuromuscular disorders characterized by clinical features of a congenital myopathy and abundant central nuclei as the most prominent histopathological feature. The most common forms of congenital myopathies with central nuclei have been attributed to X-linked recessive mutations in the MTM1 gene encoding myotubularin (“X-linked myotubular myopathy”), autosomal-dominant mutations in the DNM2 gene encoding dynamin-2 and the BIN1 gene encoding amphiphysin-2 (also named bridging integrator-1, BIN1, or SH3P9), and autosomal-recessive mutations in BIN1, the RYR1 gene encoding the skeletal muscle ryanodine receptor, and the TTN gene encoding titin. Models to study and rescue the affected cellular pathways are now available in yeast, C. elegans, drosophila, zebrafish, mouse, and dog. Defects in membrane trafficking have emerged as a key pathogenic mechanisms, with aberrant T-tubule formation, abnormalities of triadic assembly, and disturbance of the excitation–contraction machinery the main downstream effects studied to date. Abnormal autophagy has recently been recognized as another important collateral of defective membrane trafficking in different genetic forms of CNM, suggesting an intriguing link to primary disorders of defective autophagy with overlapping histopathological features. The following review will provide an overview of clinical, histopathological, and genetic aspects of the CNMs in the context of the key pathogenic mechanism, outline unresolved questions, and indicate promising future lines of enquiry. PMID:25566070

  8. Modulation of NF-?B signalling by microbial pathogens

    Microsoft Academic Search

    Masmudur M. Rahman; Grant McFadden

    2011-01-01

    The nuclear factor-?B (NF-?B) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-?B proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-?B signalling

  9. Evolution of plant pathogenicity in Streptomyces.

    PubMed

    Loria, Rosemary; Kers, Johan; Joshi, Madhumita

    2006-01-01

    Among the multitude of soil-inhabiting, saprophytic Streptomyces species are a growing number of plant pathogens that cause economically important diseases, including potato scab. Streptomyces scabies is the dominant pathogenic species worldwide, but is only one of many that cause very similar disease symptoms on plants. Molecular genetic analysis is beginning to identify the mechanisms used by plant pathogenic species to manipulate their hosts. The nitrated dipeptide phytotoxin, thaxtomin, inhibits cellulose biosynthesis in expanding plant tissues, stimulates Ca2+ spiking, and causes cell death. A secreted necrogenic protein, Nec1, contributes to virulence on diverse plant species. The thaxtomin biosynthetic genes and nec1 lie on a large mobilizable PAI, along with other putative virulence genes including a cytokinin biosynthetic pathway and a saponinase homolog. The PAI is mobilized during conjugation and site-specifically inserts in the linear chromosome of recipient species, accounting for the emergence of new pathogens in agricultural systems. The recently available genome sequence of S. scabies will accelerate research on host-pathogen interactions. PMID:16719719

  10. Opportunistic respiratory pathogens in the oral cavity of the elderly.

    PubMed

    Tada, Akio; Hanada, Nobuhiro

    2010-10-01

    The oral cavity of the hospitalized or bedridden elderly is often a reservoir for opportunistic pathogens associated with respiratory diseases. Commensal flora and the host interact in a balanced fashion and oral infections are considered to appear following an imbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. The definition of the process involved in colonization by opportunistic respiratory pathogens needs to elucidate the factors responsible for the transition of the microbiota from commensal to pathogenic flora. The regulatory factors influencing the oral ecosystem can be divided into three major categories: the host defense system, commensal bacteria, and external pathogens. In this article, we review the profile of these categories including the intricate cellular interaction between immune factors and commensal bacteria and the disturbance in homeostasis in the oral cavity of hospitalized or bedridden elderly, which facilitates oral colonization by opportunistic respiratory pathogens. PMID:20579096

  11. Pathway Analysis

    Cancer.gov

    Surprising failures of new cancer treatments have made it clear that we do not know enough about how molecules in RAS signaling pathways interact with each other. For example, in the context of mutant KRAS, inhibitors of BRAF increase signaling through ERK. RAS Initiative scientists at the FNLCR are expanding our knowledge of signaling through RAS pathways using in silico and wet lab methods.

  12. Global Expression Studies of Yersinia Pestis Pathogenicity

    SciTech Connect

    Garcia, E; Motin, V; Brubaker, R; Fitch, P

    2002-10-15

    The aim of these studies continues to be the investigation into the molecular mechanisms that underlie the virulence process in Yersinia pestis. In particular, the focus of this work centers on the identification of novel genes and pathways responsible for the pathogenic properties of this organism. In spite of more than four decades of intense investigation in this field, the dilemma as to what makes Y. pestis such a virulent and lethal pathogen remains unanswered. The method being employed makes use microarray technology (DNA chip) that enables the examination of the global activities of the whole complement of genes in this pathogen. Two primary resources available to the investigators (one directly obtained from a separate CBNP-funded project) make these studies possible: (1) Whole genome comparisons of the genes in Y. pestis and its near neighbors with attenuated or non pathogenic characteristics, and (2) the ability to duplicate in vitro, conditions that mimic the infection process of this pathogen. This year we have extended our studies from the original work of characterizing the global transcriptional regulation in Y. pestis triggered during temperature transition from 26 C to 37 C (roughly conditions found in the flea vector and the mammalian host, respectively) to studies of regulation encountered during shift between growth from conditions of neutral pH to acidic pH (the latter conditions, those mimic the environment found inside macrophages, a likely environment found by these cells during infection.). For this work, DNA arrays containing some 5,000 genes (the entire genome of Y. pestis plus those genes found uniquely in the enteropathogen, and near neighbor, Y. pseudotuberculosis) are used to monitor the simultaneous expression levels of each gene of known and unknown function in Y. pestis. Those genes that are up-regulate under the experimental conditions represent genes potentially involved in the pathogenic process. The ultimate role in pathogenicity of those candidate genes uncovered from these studies will be further ascertained by direct knock outs (gene inactivation) and by in vivo studies using an animal model. Discovery of new virulence factors in Y. pestis will directly impact the development of new signatures for detection and geo-location since it will help us to understand and identify those genes that are essential in making the organism pathogenic. These are genes that cannot be altered or removed from the pathogen and as such constitute the best type of signature that we can utilize in their detection and identification. Applications such as this will also enable the utilization of similar technologies to study other pathogens such as Francisella and Brucella, for which we know substantially less in terms of their modality of virulence.

  13. RAB11-mediated trafficking in host-pathogen interactions.

    PubMed

    Guichard, Annabel; Nizet, Victor; Bier, Ethan

    2014-09-01

    Many bacterial and viral pathogens block or subvert host cellular processes to promote successful infection. One host protein that is targeted by invading pathogens is the small GTPase RAB11, which functions in vesicular trafficking. RAB11 functions in conjunction with a protein complex known as the exocyst to mediate terminal steps in cargo transport via the recycling endosome to cell-cell junctions, phagosomes and cellular protrusions. These processes contribute to host innate immunity by promoting epithelial and endothelial barrier integrity, sensing and immobilizing pathogens and repairing pathogen-induced cellular damage. In this Review, we discuss the various mechanisms that pathogens have evolved to disrupt or subvert RAB11-dependent pathways as part of their infection strategy. PMID:25118884

  14. Microbial risk assessment in heterogeneous aquifers: 1. Pathogen transport

    NASA Astrophysics Data System (ADS)

    Molin, S.; Cvetkovic, V.

    2010-05-01

    Pathogen transport in heterogeneous aquifers is investigated for microbial risk assessment. A point source with time-dependent input of pathogens is assumed, exemplified as a simple on-site sanitation installation, intermingled with water supply wells. Any pathogen transmission pathway (realization) to the receptor from a postulated infection hazard is viewed as a random event, with the hydraulic conductivity varying spatially. For aquifers where VAR[lnK] < 1 and the integral scale is finite, we provide relatively simple semianalytical expressions for pathogen transport that incorporate the colloid filtration theory. We test a wide range of Damkohler numbers in order to assess the significance of rate limitations on the aquifer barrier function. Even slow immobile inactivation may notably affect the retention of pathogens. Analytical estimators for microbial peak discharge are evaluated and are shown to be applicable using parameters representative of rotavirus and Hepatitis A with input of 10-20 days duration.

  15. Signaling pathways in rheumatoid arthritis

    Microsoft Academic Search

    Jean-Marc Waldburger; Gary S. Firestein

    Signaling pathways orchestrate the inflammatory response by regulating various cellular functions such as programmed cell\\u000a death, cell differentiation and proliferation or secretion of signaling molecules. They are classically activated by ligand\\u000a engagement of surface receptors but increasing evidence suggests that intracellular proteins can also detect danger signals.\\u000a Protection from pathogens, chemical or physical injury, or neoplasia relies on a tightly

  16. Microarrays for Pathogen Detection and Analysis

    PubMed Central

    2011-01-01

    DNA microarrays have emerged as a viable platform for detection of pathogenic organisms in clinical and environmental samples. These microbial detection arrays occupy a middle ground between low cost, narrowly focused assays such as multiplex PCR and more expensive, broad-spectrum technologies like high-throughput sequencing. While pathogen detection arrays have been used primarily in a research context, several groups are aggressively working to develop arrays for clinical diagnostics, food safety testing, environmental monitoring and biodefense. Statistical algorithms that can analyze data from microbial detection arrays and provide easily interpretable results are absolutely required in order for these efforts to succeed. In this article, we will review the most promising array designs and analysis algorithms that have been developed to date, comparing their strengths and weaknesses for pathogen detection and discovery. PMID:21930658

  17. Proteomics of bacterial pathogens.

    PubMed

    Cash, Phillip

    2003-01-01

    The rapid growth of proteomics that has been built upon the available bacterial genome sequences has opened provided new approaches to the analysis of bacterial functional genomics. In the study of pathogenic bacteria the combined technologies of genomics, proteomics and bioinformatics has provided valuable tools for the study of complex phenomena determined by the action of multiple gene sets. The review considers some of the recent developments in the establishment of proteomic databases as well as attempts to define pathogenic determinants at the level of the proteome for some of the major human pathogens. Proteomics can also provide practical applications through the identification of immunogenic proteins that may be potential vaccine targets as well as in extending our understanding of antibiotic action. There is little doubt that proteomics has provided us with new and valuable information on bacterial pathogens and will continue to be an important source of information in the coming years. PMID:12934927

  18. Human Pathogen Importation Importing "Human" Pathogens from Outside Canada

    E-print Network

    Human Pathogen Importation Importing "Human" Pathogens from Outside Canada 1) Permits.gc.ca/ols-bsl/pathogen/index.html and scroll to the bottom of the page where you can download the "Application for Permit to Import Human Human Pathogens" and "CL2 Checklist" to PHAC at (613) 941-0596. There are no fees for this service. 5

  19. Bacterial inhibition of eukaryotic pro-inflammatory pathways

    Microsoft Academic Search

    Andrew S. Neish

    2004-01-01

    Eukaryotic cells perceive and respond to microbes, both pathogenic and commensal, by activation of signaling cascades such\\u000a as the NF-K B pathway. Induction of such pathways leads to the upregulation of a program of gene expression that mediates pro-inflammatory\\u000a and anti-apoptotic effector proteins. This host response is usually effective in clearing or controlling an infection. For\\u000a pathogens (and potentially, symbionts)

  20. ICT Pathways

    NSDL National Science Digital Library

    This page, from the Mid-Pacific Information and Communications Technology Center, provides a useful diagram for ICT educators that highlights employment pathways for students pursuing this career track. Users may click on the diagram to view a larger version.

  1. A more flexible lipoprotein sorting pathway.

    PubMed

    Chahales, Peter; Thanassi, David G

    2015-05-15

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. PMID:25755190

  2. Studying host-pathogen interactions and innate immunity in Caenorhabditis elegans

    E-print Network

    Kim, Dennis H.

    The genetic analysis of mechanisms of pathogen resistance in the nematode Caenorhabditis elegans has revealed a role for evolutionarily conserved signaling pathways that are required for innate immunity in a wide range of ...

  3. Emerging Pathogens – How Safe is Blood?

    PubMed Central

    Schmidt, Michael; Geilenkeuser, Wolf-Jochen; Sireis, Walid; Seifried, Erhard; Hourfar, Kai

    2014-01-01

    Summary During the last few decades, blood safety efforts were mainly focused on preventing viral infections. However, humanity's increased mobility and improved migration pathways necessitate a global perspective regarding other transfusion-transmitted pathogens. This review focuses on the general infection risk of blood components for malaria, dengue virus, Trypanosoma cruzi (Chagas disease) and Babesia spp. Approximately 250 million people become infected by Plasmodium spp. per year. Dengue virus affects more than 50 million people annually in more than 100 countries; clinically, it can cause serious diseases, such as dengue haemorrhagic fever and dengue shock syndrome. Chagas disease, which is caused by Trypanosoma cruzi, mainly occurs in South America and infects approximately 10 million people annually. Babesia spp. is a parasitic infection that infects red blood cells; although many infections are asymptomatic, severe clinical disease has been reported, especially in the elderly. Screening assays are available for all considered pathogens but make screening strategies more complex and more expensive. A general pathogen inactivation for all blood components (whole blood) promises to be a long-term, sustainable solution for both known and unknown pathogens. Transfusion medicine therefore eagerly awaits such a system. PMID:24659943

  4. Cell Host & Microbe Short Article

    E-print Network

    Nizet, Victor

    Cell Host & Microbe Short Article The IL-8 Protease SpyCEP/ScpC of Group A Streptococcus Promotes and immu- nostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called Scp show that the zoonotic pathogen Streptococcus iniae possesses a func- tional homolog of SpyCEP (Cep

  5. Original article Ecopathology in aquaculture

    E-print Network

    Paris-Sud XI, Université de

    Original article Ecopathology in aquaculture: risk factors in infectious disease outbreak * C, production system, season and water temperature, but their role depends on the disease. aquaculture / ecopathology / risk factor / fish / pathogen / environment Résumé ― Ã?copathologie en aquaculture

  6. Evolution of microbial pathogens.

    PubMed Central

    Morschhäuser, J; Köhler, G; Ziebuhr, W; Blum-Oehler, G; Dobrindt, U; Hacker, J

    2000-01-01

    Various genetic mechanisms including point mutations, genetic rearrangements and lateral gene transfer processes contribute to the evolution of microbes. Long-term processes leading to the development of new species or subspecies are termed macroevolution, and short-term developments, which occur during days or weeks, are considered as microevolution. Both processes, macro- and microevolution need horizontal gene transfer, which is particularly important for the development of pathogenic microorganisms. Plasmids, bacteriophages and so-called pathogenicity islands (PAIs) play a crucial role in the evolution of pathogens. During microevolution, genome variability of pathogenic microbes leads to new phenotypes, which play an important role in the acute development of an infectious disease. Infections due to Staphylococcus epidermidis, Candida albicans and Escherichia coli will be described with special emphasis on processes of microevolution. In contrast, the development of PAIs is a process involved in macroevolution. PAIs are especially important in processes leading to new pathotypes or even species. In this review, particular attention will be given to the fact that the evolution of pathogenic microbes can be considered as a specific example for microbial evolution in general. PMID:10874741

  7. Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis

    Microsoft Academic Search

    J. M. Carlton; R. P. Hirt; J. C. Silva; A. L. Delcher; Michael Schatz; Qi Zhao; J. R. Wortman; S. L. Bidwell; U. C. M. Alsmark; Sébastien Besteiro; Thomas Sicheritz-Ponten; C. J. Noel; J. B. Dacks; P. G. Foster; Cedric Simillion; Y. Van de Peer; Diego Miranda-Saavedra; G. J. Barton; G. D. Westrop; S. Muller; Daniele Dessi; P. L. Fiori; Qinghu Ren; Ian Paulsen; Hanbang Zhang; F. D. Bastida-Corcuera; Augusto Simoes-Barbosa; M. T. Brown; R. D. Hayes; Mandira Mukherjee; C. Y. Okumura; Rachel Schneider; A. J. Smith; Stepanka Vanacova; Maria Villalvazo; B. J. Haas; Mihaela Pertea; Tamara V. Feldblyum; T. R. Utterback; Chung-Li Shu; Kazutoyo Osoegawa; P. J. de Jong; Ivan Hrdy; Lenka Horvathova; Zuzana Zubacova; Pavel Dolezal; Shehre-Banoo Malik; J. M. Logsdon; Katrin Henze; Arti Gupta; Ching C. Wang; R. L. Dunne; J. A. Upcroft; Peter Upcroft; Owen White; S. L. Salzberg; Petrus Tang; Cheng-Hsun Chiu; Ying-Shiung Lee; T. M. Embley; G. H. Coombs; J. C. Mottram; Jan Tachezy; C. M. Fraser-Liggett; P. J. Johnson

    2007-01-01

    We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the ~160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated

  8. Neopolyploidy and pathogen resistance

    PubMed Central

    Oswald, Benjamin P; Nuismer, Scott L

    2007-01-01

    Despite the well-documented historical importance of polyploidy, the mechanisms responsible for the establishment and evolutionary success of novel polyploid lineages remain unresolved. One possibility, which has not been previously evaluated theoretically, is that novel polyploid lineages are initially more resistant to pathogens than the diploid progenitor species. Here, we explore this possibility by developing and analysing mathematical models of interactions between newly formed polyploid lineages and their pathogens. We find that for the genetic mechanisms of pathogen resistance with the best empirical support, newly formed polyploid populations of hosts are expected to be more resistant than their diploid progenitors. This effect can be quite strong and, in the case of perennial species with recurrent polyploid formation, may last indefinitely, potentially providing a general explanation for the successful establishment of novel polyploid lineages. PMID:17686733

  9. Pathways of antigen processing.

    PubMed

    Blum, Janice S; Wearsch, Pamela A; Cresswell, Peter

    2013-01-01

    T cell recognition of antigen-presenting cells depends on their expression of a spectrum of peptides bound to major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I- and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review, we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced. PMID:23298205

  10. MICROBIOLOGY: A Pathogen Attacks While Keeping Up Defense

    NSDL National Science Digital Library

    Staffan Normark (Karolinska Institute; Microbiology and Tumor Biology Center)

    2005-02-25

    Access to the article is free, however registration and sign-in are required. Certain species of Shigella and Yersinia bacteria are serious human pathogens. In a Perspective, Normark and colleagues discuss two exciting studies (West et al., Mota et al.) that shed light on the mechanisms enabling Shigella and Yersinia to invade host target cells. The new work may pave the way to designing new therapeutics to block invasion of host cells by these human pathogens.

  11. Immune pathways and defence mechanisms in honey bees Apis mellifera

    Microsoft Academic Search

    J. D. Evans; K. Aronstein; Y. P. Chen; C. Hetru; J.-L. Imler; H. Jiang; M. Kanost; G. J. Thompson; Z. Zou; D. Hultmark

    2006-01-01

    Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera . We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When

  12. DISINFECTION OF EMERGING PATHOGENS

    EPA Science Inventory

    There is a growing awareness of the need to control waterborne microbial pathogens. This presentation will concentate on the role of chemical inactivation, using chlorine, chloramines and ozone as a means of controlling bacterial and protozoan species. Information will be present...

  13. Pathogenicity and virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many pathogenic microorganisms are host-specific in that they parasitize only one or a few animal species. For example, the cause of equine strangles, Streptococcus equi subspecies equi, is essentially limited to infection of horses. Others—certain Salmonella serotypes, for example—have a broad host...

  14. The pathogenic equine streptococci

    Microsoft Academic Search

    John F. Timoney

    2004-01-01

    Streptococci pathogenic for the horse include S. equi (S. equi subsp. equi), S. zooepidemicus (S. equi subsp. zooepidemicus), S. dysgalactiae subsp. equisimilis and S. pneumoniae capsule Type III. S. equi is a clonal descendent or biovar of an ancestral S. zooepidemicus strain with which it shares greater than 98% DNA homology and therefore expresses many of the same proteins and

  15. PATHOGEN EQUIVALENCY COMMITTEE (PEC)

    EPA Science Inventory

    The U.S. Environmental Protection Agency created the PEC in 1985 to make recommendations to EPA and State managers on the equivalency of unproven sewage sludge disinfection technologies/processes to either a Process to Significantly Reduce Pathogens (PSRP) or a Process to Further...

  16. Leafhopper viral pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four newly discovered viral pathogens in leafhopper vectors of Pierce’s disease of grapes, have been shown to replicate in sharpshooter leafhoppers; the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, and Oncometopia nigricans (Hemiptera: Cicadellidae). The viruses were classified as memb...

  17. Lipid-derived signals that discriminate wound- and pathogen-responsive isoprenoid pathways in plants: methyl jasmonate and the fungal elicitor arachidonic acid induce different 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes and antimicrobial isoprenoids in Solanum tuberosum L.

    PubMed Central

    Choi, D; Bostock, R M; Avdiushko, S; Hildebrand, D F

    1994-01-01

    Induction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR; EC 1.1.1.34) is essential for the synthesis of steroid derivatives and sesquiterpenoid phytoalexins in solanaceous plants following mechanical injury or pathogen infection. Gene-specific probes corresponding to different HMGR genes (hmg1 and hmg2) were used to study HMGR expression in potato tissue following treatment with methyl jasmonate, a lipoxygenase product of linolenic acid, or arachidonic acid, an elicitor present in the lipids of the potato late blight fungus Phytophthora infestans. Treatment of potato discs (2.2 cm in diameter) with low concentrations (0.45-45 nmol per disc surface) of methyl jasmonate nearly doubled the wound-induced accumulation of hmg1 transcripts and steroid-glycoalkaloid (SGA) accumulation, reduced the abundance of hmg2 transcripts, and did not induce phytoalexins. High concentrations of methyl jasmonate (2-4.5 mol per disc surface) suppressed hmg1 mRNA and SGA accumulation but did not affect hmg2 mRNA abundance or induce phytoalexins. In contrast, arachidonate treatment strongly suppressed hmg1 and strongly induced hmg2 mRNA in a concentration-dependent manner. There was a corresponding suppression of SGA accumulation and an induction of sesquiterpene phytoalexin accumulation by this elicitor. Lipoxygenase inhibitors reduced the wound-induced accumulation of hmg1 transcripts and suppressed SGA levels, effects that were overcome by exogenous methyl jasmonate (45 nmol per disc surface). The results (i) suggest that methyl jasmonate can function as a signal for hmg1 expression and SGA induction following wounding and (ii) indicate that the arachidonate- and jasmonate-response pathways are distinct in relation to HMGR gene expression and isoprenoid product accumulation. The results also are consistent with placement of the HMGR activities encoded by hmg1 and hmg2 within discrete steroid and sesquiterpenoid biosynthetic channels. Images PMID:11607466

  18. Bioterrorism Articles

    NSDL National Science Digital Library

    The Journal of the American Medical Association (JAMA) is offering free access to a large number of its previously published articles related to bioterrorism. Among the articles are five pieces by the Working Group on Civilian Biodefense, which are focused on Anthrax, Smallpox, Plague, Botulinum Toxin, and Tularemia. The remainder of the articles are sorted by subject, including these diseases plus Ebola and Brucella, as well as Clinical Articles, Epidemiologic Investigations, articles on Preparedness, and a section devoted to Policy, Historical, and Editorial Perspectives. Articles are available in HTML or .pdf formats.

  19. Pathway 1.0.3

    NSDL National Science Digital Library

    Lorson, Dennis

    2007-01-01

    Sometimes wandering through the wilds of Wikipedia can result in confusion. For Dennis Lorson, his wandering led him to create this handy application. With Pathway 1.0.3 visitors can retrace their own steps through Wikipedia by creating a graphical network representation of article pages. It's worth a try, and it will work with all computers running Mac OS X 10.4.

  20. Exotic insect pests and pathogens pose the most serious current threat to the forests of eastern North

    E-print Network

    Berkowitz, Alan R.

    Articles Exotic insect pests and pathogens pose the most serious current threat to the forests of eastern North America.The litany of pest and pathogen introductions is long; it includes well of many of these pests and pathogens has been studied to the extent that researchers know (or are learning

  1. The Pathway Tools Software in 2009

    Microsoft Academic Search

    Peter D. Karp; Suzanne M. Paley; Markus Krummenacker; Mario Latendresse; Joseph M. Dale; Tom Lee; Pallavi Kaipa; Fred Gilham; Aaron Spaulding; Liviu Popescu; Tomer Altman; Ian Paulsen; Ingrid M. Keseler; Ron Caspi

    2009-01-01

    Abstract Pathway Tools is a production-quality software environment for creating a type of model- organism database (MOD) called a Pathway\\/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network, and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction

  2. Insect Vectors of Human Pathogens

    NSDL National Science Digital Library

    0000-00-00

    Four orders of insects (Hemiptera, Phthiraptera, Diptera, and Siphonaptera) are covered detailing vector species along with their pathogens of human importance. Links to pathogens as well as vectors are highlighted (some of these are CDC, and WHO).

  3. Pathways to Pathological Gambling: Identifying Typologies

    Microsoft Academic Search

    Alex Blaszczynski

    2000-01-01

    The majority of explanatory models of pathological gambling fail to differentiate specific typologies of gamblers despite recognition of the multi-factorial causal pathways to its development. All models inherently assume that gamblers are a homogenous population; therefore theoretically derived treatments can be effectively applied to all pathological gamblers. This article describes a comprehensive and alternative conceptual-pathway model that identifies three main

  4. Multiplex detection of agricultural pathogens

    DOEpatents

    Siezak, Thomas R.; Gardner, Shea; Torres, Clinton; Vitalis, Elizabeth; Lenhoff, Raymond J.

    2013-01-15

    Described are kits and methods useful for detection of agricultural pathogens in a sample. Genomic sequence information from agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay and/or an array assay to successfully identify the presence or absence of pathogens in a sample.

  5. Multiplex detection of agricultural pathogens

    DOEpatents

    McBride, Mary Teresa (Brentwood, CA); Slezak, Thomas Richard (Livermore, CA); Messenger, Sharon Lee (Kensington, CA)

    2010-09-14

    Described are kits and methods useful for detection of seven agricultural pathogens (BPSV; BHV; BVD; FMDV; BTV; SVD; and VESV) in a sample. Genomic sequence information from 7 agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  6. Microbial Pathogens in the Fungal Kingdom

    PubMed Central

    Heitman, Joseph

    2011-01-01

    The fungal kingdom is vast, spanning ~1.5 to as many as 5 million species diverse as unicellular yeasts, filamentous fungi, mushrooms, lichens, and both plant and animal pathogens. The fungi are closely aligned with animals in one of the six to eight supergroups of eukaryotes, the opisthokonts. The animal and fungal kingdoms last shared a common ancestor ~1 billion years ago, more recently than other groups of eukaryotes. As a consequence of their close evolutionary history and shared cellular machinery with metazoans, fungi are exceptional models for mammalian biology, but prove more difficult to treat in infected animals. The last common ancestor to the fungal/metazoan lineages is thought to have been unicellular, aquatic, and motile with a posterior flagellum, and certain extant species closely resemble this hypothesized ancestor. Species within the fungal kingdom were traditionally assigned to four phyla, including the basal fungi (Chytridiomycota, Zygomycota) and the more recently derived monophyletic lineage, the dikarya (Ascomycota, Basidiomycota). The fungal tree of life project has revealed that the basal lineages are polyphyletic, and thus there are as many as eight to ten fungal phyla. Fungi that infect vertebrates are found in all of the major lineages, and virulence arose multiple times independently. A sobering recent development involves the species Batrachochytrium dendrobatidis from the basal fungal phylum, the Chytridiomycota, which has emerged to cause global amphibian declines and extinctions. Genomics is revolutionizing our view of the fungal kingdom, and genome sequences for zygomycete pathogens (Rhizopus, Mucor), skin-associated fungi (dermatophytes, Malassezia), and the Candida pathogenic species clade promise to provide insights into the origins of virulence. Here we survey the diversity of fungal pathogens and illustrate key principles revealed by genomics involving sexual reproduction and sex determination, loss of conserved pathways in derived fungal lineages that are retained in basal fungi, and shared and divergent virulence strategies of successful human pathogens, including dimorphic and trimorphic transitions in form. The overarching conclusion is that fungal pathogens of animals have arisen repeatedly and independently throughout the fungal tree of life, and while they share general properties, there are also unique features to the virulence strategies of each successful microbial pathogen. PMID:21528015

  7. Ecology of Waterborne Pathogens Instructor

    E-print Network

    Ma, Lena

    Ecology of Waterborne Pathogens Instructor: Max Teplitski, Associate Professor Phone: 273 Prerequisites: MCB3020 (Basic Biology of Microorganisms), or MCB3023 or MCB4203 (Bacterial and Viral Pathogens and methodologies for identifying and characterizing pathogens and their behaviors outside of their human hosts

  8. Pathogenicity Islands in Bacterial Pathogenesis

    PubMed Central

    Schmidt, Herbert; Hensel, Michael

    2004-01-01

    In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections. PMID:14726454

  9. Chitosan against cutaneous pathogens

    PubMed Central

    2013-01-01

    Propionibacterium acnes and Staphylococcus aureus are cutaneous pathogens that have become increasingly resistant to antibiotics. We sought to determine if chitosan, a polymer of deacetylated chitin, could be used as a potential treatment against these bacteria. We found that higher molecular weight chitosan had superior antimicrobial properties compared to lower molecular weights, and that this activity occurred in a pH dependent manner. Electron and fluorescence microscopy revealed that chitosan forms aggregates and binds to the surface of bacteria, causing shrinkage of the bacterial membrane from the cell wall. Of special relevance, clinical isolates of P. acnes were vulnerable to chitosan, which could be combined with benzoyl peroxide for additive antibacterial effect. Chitosan also demonstrated significantly less cytotoxicity to monocytes than benzoyl peroxide. Overall, chitosan demonstrates many promising qualities for treatment of cutaneous pathogens. PMID:23829873

  10. Adhesion by Pathogenic Corynebacteria

    Microsoft Academic Search

    Elizabeth A. Rogers; Asis Das; Hung Ton-That

    \\u000a Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during\\u000a infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial\\u000a cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and

  11. Stress Response and Pathogenicity of the Necrotrophic Fungal Pathogen Alternaria alternata

    PubMed Central

    Chung, Kuang-Ren

    2012-01-01

    The production of host-selective toxins by the necrotrophic fungus Alternaria alternata is essential for the pathogenesis. A. alternata infection in citrus leaves induces rapid lipid peroxidation, accumulation of hydrogen peroxide (H2O2), and cell death. The mechanisms by which A. alternata avoids killing by reactive oxygen species (ROS) after invasion have begun to be elucidated. The ability to coordinate of signaling pathways is essential for the detoxification of cellular stresses induced by ROS and for pathogenicity in A. alternata. A low level of H2O2, produced by the NADPH oxidase (NOX) complex, modulates ROS resistance and triggers conidiation partially via regulating the redox-responsive regulators (YAP1 and SKN7) and the mitogen-activated protein (MAP) kinase (HOG1) mediated pathways, which subsequently regulate the genes required for the biosynthesis of siderophore, an iron-chelating compound. Siderophore-mediated iron acquisition plays a key role in ROS detoxification because of the requirement of iron for the activities of antioxidants (e.g., catalase and SOD). Fungal strains impaired for the ROS-detoxifying system severely reduce the virulence on susceptible citrus cultivars. This paper summarizes the current state of knowledge of signaling pathways associated with cellular responses to multidrugs, oxidative and osmotic stress, and fungicides, as well as the pathogenicity/virulence in the tangerine pathotype of A. alternata. PMID:24278721

  12. PIPS: Pathogenicity Island Prediction Software

    PubMed Central

    Soares, Siomar C.; Abreu, Vinícius A. C.; Ramos, Rommel T. J.; Cerdeira, Louise; Silva, Artur; Baumbach, Jan; Trost, Eva; Tauch, Andreas; Hirata, Raphael; Mattos-Guaraldi, Ana L.; Miyoshi, Anderson; Azevedo, Vasco

    2012-01-01

    The adaptability of pathogenic bacteria to hosts is influenced by the genomic plasticity of the bacteria, which can be increased by such mechanisms as horizontal gene transfer. Pathogenicity islands play a major role in this type of gene transfer because they are large, horizontally acquired regions that harbor clusters of virulence genes that mediate the adhesion, colonization, invasion, immune system evasion, and toxigenic properties of the acceptor organism. Currently, pathogenicity islands are mainly identified in silico based on various characteristic features: (1) deviations in codon usage, G+C content or dinucleotide frequency and (2) insertion sequences and/or tRNA genetic flanking regions together with transposase coding genes. Several computational techniques for identifying pathogenicity islands exist. However, most of these techniques are only directed at the detection of horizontally transferred genes and/or the absence of certain genomic regions of the pathogenic bacterium in closely related non-pathogenic species. Here, we present a novel software suite designed for the prediction of pathogenicity islands (pathogenicity island prediction software, or PIPS). In contrast to other existing tools, our approach is capable of utilizing multiple features for pathogenicity island detection in an integrative manner. We show that PIPS provides better accuracy than other available software packages. As an example, we used PIPS to study the veterinary pathogen Corynebacterium pseudotuberculosis, in which we identified seven putative pathogenicity islands. PMID:22355329

  13. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms

    PubMed Central

    Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance. PMID:24137567

  14. Tick vaccines and the control of tick-borne pathogens

    PubMed Central

    Merino, Octavio; Alberdi, Pilar; Pérez de la Lastra, José M.; de la Fuente, José

    2013-01-01

    Ticks are obligate hematophagous ectoparasites that transmit a wide variety of pathogens to humans and animals. The incidence of tick-borne diseases has increased worldwide in both humans and domestic animals over the past years resulting in greater interest in the study of tick-host-pathogen interactions. Advances in vector and pathogen genomics and proteomics have moved forward our knowledge of the vector-pathogen interactions that take place during the colonization and transmission of arthropod-borne microbes. Tick-borne pathogens adapt from the vector to the mammalian host by differential gene expression thus modulating host processes. In recent years, studies have shown that targeting tick proteins by vaccination can not only reduce tick feeding and reproduction, but also the infection and transmission of pathogens from the tick to the vertebrate host. In this article, we review the tick-protective antigens that have been identified for the formulation of tick vaccines and the effect of these vaccines on the control of tick-borne pathogens. PMID:23847771

  15. MICROBIOLOGY: Enhanced: A Furtive Pathogen Revealed

    NSDL National Science Digital Library

    Xavier Nassif (Faculté de Médecine Necker-Enfants Malades; INSERM Unit 411)

    2000-03-10

    Access to the article is free, however registration and sign-in are required: The pathogenic bacterium Neisseria meningitidis is the cause of meningococcal meningitis. Although a vaccine is available for Neisseria of serogroups A and C, there is no vaccine available for serogroup B. In a Perspective, Nassif reports on the sequencing of the complete genome of N. meningitidis type B strain MC58 (Tettelin et al.) and the mining of this genome to identify highly conserved surface proteins that may be valuable as vaccine antigens (Pizza et al.).

  16. MICROBIOLOGY: Enhanced: Pathogenic Bacteria Prefer Heme

    NSDL National Science Digital Library

    Tracey A. Rouault (National Institute of Child Health and Human Development; Human Iron Metabolism, Cell Biology and Metabolism Branch)

    2004-09-10

    Access to the article is free, however registration and sign-in are required. Bloodletting by physicians before the era of antibiotics may seem like a barbaric practice, but it may have been of some benefit to patients suffering from bacterial infections. In her Perspective, Rouault explains that most bacteria depend on a source of iron to grow and survive inside their animal hosts. A new study (Skaar et al.) shows that the pathogenic bacterium Staphylococcus aureus uses several ingenious strategies to obtain iron from heme stored as hemoglobin in the red blood cells of its mammalian hosts.

  17. Fusobacterium nucleatum: a commensal-turned pathogen.

    PubMed

    Han, Yiping W

    2015-02-01

    Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen associated with a wide spectrum of human diseases. This article reviews its implication in adverse pregnancy outcomes (chorioamnionitis, preterm birth, stillbirth, neonatal sepsis, preeclampsia), GI disorders (colorectal cancer, inflammatory bowel disease, appendicitis), cardiovascular disease, rheumatoid arthritis, respiratory tract infections, Lemierre's syndrome and Alzheimer's disease. The virulence mechanisms involved in the diseases are discussed, with emphasis on its colonization, systemic dissemination, and induction of host inflammatory and tumorigenic responses. The FadA adhesin/invasin conserved in F. nucleatum is a key virulence factor and a potential diagnostic marker for F. nucleatum-associated diseases. PMID:25576662

  18. Portable pathogen detection system

    DOEpatents

    Milanovich, Fred P.; Brown, Steve B.; Colston, Billy W.; Everett, Matthew; Vendateswaran, Kodumudi; Simon, Jonathan N.

    2005-06-14

    A portable pathogen detection system that accomplishes on-site multiplex detection of targets in biological samples. The system includes: microbead specific reagents, incubation/mixing chambers, a disposable microbead capture substrate, and an optical measurement and decoding arrangement. The basis of this system is a highly flexible Liquid Array that utilizes optically encoded microbeads as the templates for biological assays. Target biological samples are optically labeled and captured on the microbeads, which are in turn captured on an ordered array or disordered array disposable capture substrate and then optically read.

  19. BK polyomavirus: emerging pathogen

    PubMed Central

    Bennett, Shauna M.; Broekema, Nicole M.; Imperiale, Michael J.

    2013-01-01

    BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging pathogen in immunocompromised individuals. BKPyV is widespread in the general population, but primarily causes disease when immune suppression leads to reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic cystitis in renal and bone marrow transplant patients, respectively, are the most common diseases associated with BKPyV reactivation and lytic infection. In this review, we discuss the clinical relevance, effects on the host, virus life cycle, and current treatment protocols. PMID:22402031

  20. Original article Pathogenic characteristics of persistent feline enteric

    E-print Network

    Boyer, Edmond

    , Tamara GEERTS 1 , Leontine S. SCHUIJFF 1 , Guy C.M. GRINWIS 2 , Herman F. EGBERINK 1 , Peter J.M. ROTTIER 1* 1 Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated

  1. Developmental Pathways in Juvenile Externalizing and Internalizing Problems

    ERIC Educational Resources Information Center

    Loeber, Rolf; Burke, Jeffrey D.

    2011-01-01

    This article summarizes the empirical studies showing pathways in the development of externalizing and delinquent behaviors. Pathways are defined as the orderly temporal development between more than two problem behaviors. The paper addresses the following questions: (1) What are the developmental pathways between different diagnoses of Disruptive…

  2. Help-Seeking Pathways for Children and Adolescents

    Microsoft Academic Search

    DEBRA SREBNIK; ANA MARI CAUCE; NAZLI BAYDAR

    1996-01-01

    The processes by which children with emotional and behavioral disorders seek and obtain help have received little study; yet, they are critical for determining mental health policy and practice. In this article, help-seeking pathways for children are defined and a pathway model is presented. Influences on help-seeking pathways are then reviewed, including illness profile variables, predisposing factors, and barriers to

  3. Developmental Cell The Fz-Dsh Planar Cell Polarity Pathway

    E-print Network

    Prehoda, Ken

    Developmental Cell Article The Fz-Dsh Planar Cell Polarity Pathway Induces Oriented Cell Division vertebrates and inver- tebrates, the Frizzled (Fz) planar cell polarity (PCP) pathway acts to orient the cell division relative to extrinsic cues within a tissue. By doing so, the Fz PCP pathway has fundamental roles

  4. Focus on food safety: Human pathogens on plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article introduces the first Focus Issue of Phytopathology, a dedicated issue of the journal that highlights a topic of significant interest to our readership. This first Focus Issue addresses the topic of food safety and the biology of human pathogens on plants, a relatively new problem in pla...

  5. Biological Control of Plant Pathogens: Research, Commercialization, and Application in the USA

    NSDL National Science Digital Library

    Brian B. McSpadden Gardener (The Ohio State University-OARDC; )

    2002-05-10

    This article describes the current status of research, commercial development, and application of biocontrol strategies targeted at plant pathogens. Also included is a description of future prospects for using biological control to limit the damage of plant pathogens in both conventional and organic agriculture.

  6. The Type I Interferon Pathway

    NSDL National Science Digital Library

    David S. Aaronson (Mount Sinai School of Medicine; Immunobiology Center REV)

    2003-08-26

    The type I interferon (IFN-?/?) signal transduction pathway is not only the first-characterized Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, but one of the best studied in molecular detail. IFN-?-stimulated gene factor 3 (ISGF3) is atypical for STAT-containing complexes, because it requires interaction with an additional factor, IFN regulatory factor 9 (IRF9), to provide specific DNA binding. Type I IFN is the main innate antiviral cytokine, and the outcome of ISGF3 activation is establishment of the cellular antiviral state, in which cells are able to inhibit the replication of a broad range of virus types providing a general resistance to infection. It is increasingly evident that other branches of the innate and adaptive immune systems activate IFN-?/? signaling, indicating its importance in various stress responses. The Connections Map provides an overview of this canonical pathway, with an interpathway relation to the Toll-like Receptor Pathway, which stimulates the production of type I interferons in response to microbial pathogens. Science Viewpoint D. S. Aaronson, C. M. Horvath, A road map for those who don't know JAK-STAT. Science 296, 1653-1655 (2002). [Abstract] [Full Text

  7. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria.

    PubMed

    Behnsen, Judith; Jellbauer, Stefan; Wong, Christina P; Edwards, Robert A; George, Michael D; Ouyang, Wenjun; Raffatellu, Manuela

    2014-02-20

    Interleukin-22 (IL-22) is highly induced in response to infections with a variety of pathogens, and its main functions are considered to be tissue repair and host defense at mucosal surfaces. Here we showed that IL-22 has a unique role during infection in that its expression suppressed the intestinal microbiota and enhanced the colonization of a pathogen. IL-22 induced the expression of antimicrobial proteins, including lipocalin-2 and calprotectin, which sequester essential metal ions from microbes. Because Salmonella enterica ser. Typhimurium can overcome metal ion starvation mediated by lipocalin-2 and calprotectin via alternative pathways, IL-22 boosted its colonization of the inflamed intestine by suppressing commensal Enterobacteriaceae, which are susceptible to the antimicrobial proteins. Thus, IL-22 tipped the balance between pathogenic and commensal bacteria in favor of a pathogen. Taken together, IL-22 induction can be exploited by pathogens to suppress the growth of their closest competitors, thereby enhancing pathogen colonization of mucosal surfaces. PMID:24508234

  8. Cryptosporidium Pathogenicity and Virulence

    PubMed Central

    Bouzid, Maha; Chalmers, Rachel M.; Tyler, Kevin M.

    2013-01-01

    Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence. PMID:23297262

  9. HealthPathways: creating a pathway for health systems reform.

    PubMed

    Robinson, Suzanne; Varhol, Richard; Bell, Colin; Quirk, Frances; Durrington, Learne

    2014-12-01

    Inefficiencies in the co-ordination and integration of primary and secondary care services in Australia, have led to increases in waiting times, unnecessary presentations to emergency departments and issues around poor discharge of patients. HealthPathways is a program developed in Canterbury, New Zealand, that builds relationships between General Practitioners and Specialists and uses information technology so that efficiency is maximised and the right patient is given the right care at the right time. Healthpathways is being implemented by a number of Medicare Locals across Australia however, little is known about the impact HealthPathways may have in Australia. This article provides a short description of HealthPathways and considers what it may offer in the Australian context and some of the barriers and facilitators to implementation. What is known about the topic? Early evidence on HealthPathways suggests that the program does seem to be strengthening relationships between GPs and secondary care specialists. In New Zealand advances in efficiency and system integration have been noted. However, there is limited evidence on the effectiveness of HealthPathways in Australia. What does this paper add? It is one of the first published papers to provide a perspective around HealthPathways and draws existing evidence and research to explore some of the barriers and facilitators to the development and implementation of HealthPathways in Australia. What are the implications for practitioners'? Early evidence suggests HealthPathways could help GPs and other practitioners' in the delivery of health services, it could also help to strengthen practitioner relationships. PMID:25433515

  10. Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection.

    PubMed

    Fischer, Hans; Lutay, Nataliya; Ragnarsdóttir, Bryndís; Yadav, Manisha; Jönsson, Klas; Urbano, Alexander; Al Hadad, Ahmed; Rämisch, Sebastian; Storm, Petter; Dobrindt, Ulrich; Salvador, Ellaine; Karpman, Diana; Jodal, Ulf; Svanborg, Catharina

    2010-01-01

    The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3(-/-) mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFN?-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3(-/-) mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response. PMID:20886096

  11. Pathogen Specific, IRF3-Dependent Signaling and Innate Resistance to Human Kidney Infection

    PubMed Central

    Fischer, Hans; Lutay, Nataliya; Ragnarsdóttir, Bryndís; Yadav, Manisha; Jönsson, Klas; Urbano, Alexander; Al Hadad, Ahmed; Rämisch, Sebastian; Storm, Petter; Dobrindt, Ulrich; Salvador, Ellaine; Karpman, Diana; Jodal, Ulf; Svanborg, Catharina

    2010-01-01

    The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3?/? mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFN?-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3?/? mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response. PMID:20886096

  12. Phytotoxins produced by plant pathogenic Streptomyces species.

    PubMed

    Bignell, Dawn R D; Fyans, Joanna K; Cheng, Zhenlong

    2013-10-17

    Streptomyces is a large genus consisting of soil-dwelling, filamentous bacteria that are best known for their capability of producing a vast array of medically and agriculturally useful secondary metabolites. In addition, a small number of Streptomyces spp. are capable of colonizing and infecting the underground portions of living plants and causing economically important crop diseases such as potato common scab (CS). Research into the mechanisms of Streptomyces plant pathogenicity has led to the identification and characterization of several phytotoxic secondary metabolites that are known or suspected of contributing to diseases in various plants. The best characterized are the thaxtomin phytotoxins, which play a critical role in the development of CS, acid scab and soil rot of sweet potato. In addition, the best-characterized CS-causing pathogen, S. scabies, produces a molecule that is predicted to resemble the Pseudomonas syringae coronatine phytotoxin and which contributes to seedling disease symptom development. Other Streptomyces phytotoxic secondary metabolites that have been identified include concanamycins, FD-891 and borrelidin. Furthermore, there is evidence that additional, unknown metabolites may participate in Streptomyces plant pathogenicity. Such revelations have implications for the rational development of better management procedures for controlling CS and other Streptomyces plant diseases. This article is protected by copyright. All rights reserved. PMID:24131731

  13. Please cite this article in press as: McPherson, B.A., et al., Responses of oaks and tanoaks to the sudden oak death pathogen after 8 y of monitoring in two coastal California forests. Forest Ecol. Manage. (2010), doi:10.1016/j.foreco.2010.02.020

    E-print Network

    Standiford, Richard B.

    2010-01-01

    Phytophthora ramorum Coast live oak California black oak Tanoak a b s t r a c t Sudden oak death, caused to the sudden oak death pathogen after 8 y of monitoring in two coastal California forests. Forest Ecol. Manage death pathogen after 8 y of monitoring in two coastal California forests Brice A. McPhersona, , Sylvia R

  14. The roles of TLRs, RLRs and NLRs in pathogen recognition

    PubMed Central

    Kawai, Taro

    2009-01-01

    The mammalian innate immune system detects the presence of microbial infection through germ line-encoded pattern recognition receptors (PRRs). Toll-like receptors, retinoic acid-inducible gene-I-like receptors and nucleotide-binding oligomerization domain-like receptors serve as PRRs that recognize different but overlapping microbial components. They are expressed in different cellular compartments such as the cell surface, endosome, lysosome or cytoplasm and activate specific signaling pathways that lead to expression of genes that tailor immune responses to particular microbes. This review summarizes recent insights into pathogen sensing by these PRRs and their signaling pathways. PMID:19246554

  15. Multiplex detection of respiratory pathogens

    DOEpatents

    McBride, Mary (Brentwood, CA); Slezak, Thomas (Livermore, CA); Birch, James M. (Albany, CA)

    2012-07-31

    Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  16. Genome comparison of bacterial pathogens.

    PubMed

    Wassenaar, T M; Bohlin, J; Binnewies, T T; Ussery, D W

    2009-01-01

    Bacterial pathogens are being sequenced at an increasing rate. To many microbiologists, it appears that there simply is not enough time to digest all the information suddenly available. In this chapter we present several tools for comparison of sequenced pathogenic genomes, and discuss differences between pathogens and non-pathogens. The presented tools allow comparison of large numbers of genomes in a hypothesis-driven manner. Visualization of the results is very important for clear presentation of the results and various ways of graphical representation are introduced. PMID:19696490

  17. Alterations of host cell ubiquitination machinery by pathogenic bacteria

    PubMed Central

    Alomairi, Jaafar; Bonacci, Thomas; Ghigo, Eric; Soubeyran, Philippe

    2015-01-01

    Response of immune and non-immune cells to pathogens infections is a very dynamic process. It involves the activation/modulation of many pathways leading to actin remodeling, membrane engulfing, phagocytosis, vesicle trafficking, phagolysosome formation, aiming at the destruction of the intruder. These sophisticated and rapid mechanisms rely on post-translational modifications (PTMs) of key host cells' factors, and bacteria have developed various strategies to manipulate them to favor their survival. Among these important PTMs, ubiquitination has emerged as a major mediator/modulator/regulator of host cells response to infections that pathogens have also learned to use for their own benefit. In this mini-review, we summarize our current knowledge about the normal functions of ubiquitination during host cell infection, and we detail its hijacking by model pathogens to escape clearance and to proliferate.

  18. Discrimination between Host and Pathogens by the Complement System

    PubMed Central

    Pangburn, Michael K.; Ferreira, Viviana P.; Cortes, Claudio

    2008-01-01

    Pathogen-specific complement activation requires direct recognition of pathogens and/or the absence of complement control mechanisms on their surfaces. Antibodies direct complement activation to potential pathogens recognized by the cellular innate and adaptive immune systems. Similarly, the plasma proteins MBL and ficolins direct activation to microorganisms expressing common carbohydrate structures. The absence of complement control proteins permits amplification of complement by the alternative pathway on any unprotected surface. The importance of complement recognition molecules (MBL, ficolins, factor H, C3, C1q, properdin, and others) to human disease are becoming clear as analysis of genetic data and knock out animals reveals links between complement proteins and specific diseases. PMID:19388159

  19. Spontaneous activation of RNA-sensing pathways in autoimmune disease

    PubMed Central

    Crampton, Steve P; Bolland, Silvia

    2013-01-01

    Multiple intracellular RNA sensing innate immune pathways have been linked to autoimmune disease. RNA-related ligands taken up by the endocytic pathway activate TLRs, and affect primarily immune cells. This type of activation is enhanced by nucleic acid-specific antibodies and induces an inflammatory program. In contrast, spontaneous activation of cytoplasmic RNA sensing pathways target mostly non-hematopoietic tissues and their effect on autoimmune disease is secondary to the release of interferon in the circulation. The fact that pathologies result from spontaneous activation of innate pathways implies that endogenous RNA ligands that might be sensed as pathogenic are commonly found in both immune and non-immune cells. PMID:24455767

  20. PathogenMip Assay: A Multiplex Pathogen Detection Assay

    Microsoft Academic Search

    Michael S. Akhras; Sreedevi Thiyagarajan; Andrea C. Villablanca; Ronald W. Davis; Pål Nyrén; Nader Pourmand; Sheila Bowyer

    2007-01-01

    The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer

  1. Original article Risk factors and characteristics of H5N1

    E-print Network

    Paris-Sud XI, Université de

    Original article Risk factors and characteristics of H5N1 Highly Pathogenic Avian Influenza (HPAI) Abstract ­ Highly pathogenic avian influenza (HPAI) virus H5N1 is now endemic in South-East Asia but HPAI period. avian influenza / H5N1 / poultry / risk factor / HPAI outbreak 1. INTRODUCTION Highly pathogenic

  2. ORIGINAL ARTICLE The impact of insecticide resistance on Culex pipiens

    E-print Network

    Rivero, Ana

    ORIGINAL ARTICLE The impact of insecticide resistance on Culex pipiens immunity Julien Vezilier,1 resistance in Culex pipiens, an epidemiologically important vector of a wide array of pathogens. Using both

  3. RESEARCH ARTICLE Open Access Klebsiella pneumoniae related community-

    E-print Network

    Paris-Sud XI, Université de

    RESEARCH ARTICLE Open Access Klebsiella pneumoniae related community- acquired acute lower, Klebsiella pneumoniae (KP) is the second pathogen responsible for community-acquired pneumonia. Yet, very-sector hospitals. Keywords: Klebsiella pneumoniae, Community-acquired, Pneumonia, Extended-spectrum betalactamases

  4. Glacial refugia in pathogens: European genetic structure of anther smut pathogens on Silene latifolia and Silene dioica.

    PubMed

    Vercken, Elodie; Fontaine, Michael C; Gladieux, Pierre; Hood, Michael E; Jonot, Odile; Giraud, Tatiana

    2010-01-01

    Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns. PMID:21187901

  5. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection. PMID:25456681

  6. Alterations in protein expression and complement resistance of pathogenic Naegleria amoebae.

    PubMed Central

    Toney, D M; Marciano-Cabral, F

    1992-01-01

    Highly pathogenic strains of Naegleria fowleri activate the alternative complement pathway but are resistant to lysis. In contrast, weakly pathogenic and nonpathogenic Naegleria spp. activate the complement pathway and are readily lysed. The present study was undertaken to determine whether surface components on amoebae accounted for resistance to complement lysis. Enzymatic removal of surface components from highly pathogenic N. fowleri with phosphatidylinositol-specific phospholipase C or with endoglycosidase H increased the susceptibility of these amoebae to complement-mediated lysis. Similar treatment of nonpathogenic amoebae had no effect on susceptibility to complement. Tunicamycin treatment of highly and weakly pathogenic N. fowleri increased susceptibility to lysis by complement in a dose-related manner. Tunicamycin treatment did not alter the susceptibility of nonpathogenic amoebae to complement. Proteins of 234 and 47 kDa were detected in supernatant fluid from phosphatidylinositol-specific phospholipase C-treated highly pathogenic amoebae but not in supernatant fluid from phosphatidylinositol-specific phospholipase C-treated weakly pathogenic amoebae. Electrophoretic analysis of iodinated surface proteins of highly pathogenic N. fowleri revealed species of 89, 60, 44, and 28 kDa. Western immunoblots of lysates from surface-iodinated amoebae were stained with biotinylated concanavalin A or biotinylated Ulex europaeus agglutinin I. Surface proteins, identified in highly pathogenic amoebae by iodination, were shown to be glycoproteins by lectin analysis specific for the detection of mannose and fucose residues. Images PMID:1319405

  7. Bacteria: More Than Pathogens

    NSDL National Science Digital Library

    Trudy Wassenaar (; )

    2002-07-01

    The issue-focused, peer-reviewed article reveals that there are more bacteria on Earth than there are humans. Bacteria: inhabit every environment on the planet, playing a key ecological role, can be good for our health -- for example, by helping us digest food, and can cause disease even though the human body is not the natural host for many bacteria.

  8. Article type

    E-print Network

    2012-01-01

    PDF corresponds to the article as it appeared upon acceptance. Copyedited and fully formatted PDF and full text (HTML) versions will be made available soon. Draft genome of the mountain pine beetle, Dendroctonus ponderosae Hopkins, a major forest pest

  9. Article URL

    E-print Network

    Sagar M Goyal; Naresh Jindal; Yogesh Chander; Muthanan A Ramakrishnan; Patrick T Redig; Srinand Sreevatsan; Sagar M Goyal; Naresh Jindal; Yogesh Ch; Muthanan A Ramakrishnan; Patrick T Redig

    2010-01-01

    PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. Isolation of mixed subtypes of influenza A virus from a bald eagle (Haliaeetus leucocephalus)

  10. Pathogen Intensity Cross-Culturally

    Microsoft Academic Search

    Bobbi S. Low

    1994-01-01

    Serious pathogens represent a special category of environmental uncertainty, and one likely to have more far-reaching effects than climatic or other physical unpredictabilities with which humans must cope (e. g. Low 1988a, 1989a). Above and beyond the obvious difficulties serious pathogens represent, they have been implicated in sexual selection (Hamilton and Zuk 1982, Read 1987, 1988, Read and Harvey 1989,

  11. USEPA PATHOGEN EQUIVALENCY COMMITTEE RETREAT

    EPA Science Inventory

    The Pathogen Equivalency Committee held its retreat from September 20-21, 2005 at Hueston Woods State Park in College Corner, Ohio. This presentation will update the PEC’s membership on emerging pathogens, analytical methods, disinfection techniques, risk analysis, preparat...

  12. FOODBORNE PATHOGENS IN DAIRY ENVIRONMENTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Outbreaks of foodborne illnesses caused by pathogenic bacteria are increasingly being linked to fresh produce. Animal manure is a potential pathogen reservoir, and the close proximity of dairy operations and croplands in California cannot be ignored. We have worked on developing improved detection m...

  13. Maintenance of Vacuole Integrity by Bacterial Pathogens

    PubMed Central

    Creasey, Elizabeth A.; Isberg, Ralph R.

    2014-01-01

    Many intracellular bacterial pathogens reside within a membrane-bound compartment. The biogenesis of these vacuolar compartments is complex, involving subversion of host cell secretory pathways by bacterial proteins. In recent years it has become clear that disruption of vacuole biogenesis may result in membrane rupture and escape of bacteria into the host cell cytosol. Correct modulation of the host cell cytoskeleton, signalling molecules such as small GTPases and the lipids of the vacuole membrane have all been shown to be critical in the maintenance of vacuole integrity. Increasing evidence suggests that vacuole rupture may result from aberrant mechanical forces exerted on the vacuole, possibly due to a defect in vacuole expansion. PMID:24581692

  14. Principles of the Atmospheric Pathway for Invasive Species Applied to Soybean Rust

    NSDL National Science Digital Library

    SCOTT A. ISARD, STUART H. GAGE, PAUL COMTOIS, and JOSEPH M. RUSSO (; )

    2005-10-01

    This peer reviewed article from BioScience is about disease in soybeans. Aerial transport alone is seldom responsible for the introduction of nonindigenous species into distant regions; however, the capacity to use the atmospheric pathway for rapid spread in large part determines the invasive potential of organisms once they are introduced. Because physical and biological features of Earth's surface influence the routes and timing of organisms that use the atmospheric pathway, long-distance movement of aerobiota is largely regular and thus predictable. Soybean rust (Phakopsora pachyrhizi), potentially the most destructive foliar disease of soybean, recently invaded North America. The concepts presented in this article form the basis of the soybean rust aerobiology prediction system (SRAPS) that was developed to assess potential pathogen movement from South America to the United States. Output from SRAPS guided the scouting operations after the initial discovery of soybean rust in Louisiana. Subsequent observations of P. pachyrhizi in the southeastern United States provide validation of the modeling effort.

  15. Impact of the UPR on the virulence of the plant fungal pathogen A. brassicicola

    PubMed Central

    Guillemette, Thomas; Calmes, Benoit; Simoneau, Philippe

    2014-01-01

    The fungal genus Alternaria contains many destructive plant pathogens, including Alternaria brassicicola, which causes black spot disease on a wide range of Brassicaceae plants and which is routinely used as a model necrotrophic pathogen in studies with Arabidopsis thaliana. During host infection, many fungal proteins that are critical for disease progression are processed in the endoplasmic reticulum (ER)/Golgi system and secreted in planta. The unfolded protein response (UPR) is an essential part of ER protein quality control that ensures efficient maturation of secreted and membrane-bound proteins in eukaryotes. This review highlights the importance of the UPR signaling pathway with respect to the ability of A. brassicicola to efficiently accomplish key steps of its pathogenic life cycle. Understanding the pathogenicity mechanisms that fungi uses during infection is crucial for the development of new antifungal therapies. Therefore the UPR pathway has emerged as a promising drug target for plant disease control. PMID:24189567

  16. Optimization of proteomic sample preparation procedures for comprehensive protein characterization of pathogenic systems

    SciTech Connect

    Brewer, Heather M.; Norbeck, Angela D.; Adkins, Joshua N.; Manes, Nathan P.; Ansong, Charles; Shi, Liang; Rikihisa, Yasuko; Kikuchi, Takane; Wong, Scott; Estep, Ryan D.; Heffron, Fred; Pasa-Tolic, Ljiljana; Smith, Richard D.

    2008-12-19

    The elucidation of critical functional pathways employed by pathogens and hosts during an infectious cycle is both challenging and central to our understanding of infectious diseases. In recent years, mass spectrometry-based proteomics has been used as a powerful tool to identify key pathogenesis-related proteins and pathways. Despite the analytical power of mass spectrometry-based technologies, samples must be appropriately prepared to characterize the functions of interest (e.g. host-response to a pathogen or a pathogen-response to a host). The preparation of these protein samples requires multiple decisions about what aspect of infection is being studied, and it may require the isolation of either host and/or pathogen cellular material.

  17. The BER necessities: the repair of DNA damage in human-adapted bacterial pathogens.

    PubMed

    van der Veen, Stijn; Tang, Christoph M

    2015-02-01

    During colonization and disease, bacterial pathogens must survive the onslaught of the host immune system. A key component of the innate immune response is the generation of reactive oxygen and nitrogen species by phagocytic cells, which target and disrupt pathogen molecules, particularly DNA, and the base excision repair (BER) pathway is the most important mechanism for the repair of such oxidative DNA damage. In this Review, we discuss how the human-specific pathogens Mycobacterium tuberculosis, Helicobacter pylori and Neisseria meningitidis have evolved specialized mechanisms of DNA repair, particularly their BER pathways, compared with model organisms such as Escherichia coli. This specialization in DNA repair is likely to reflect the distinct niches occupied by these important human pathogens in the host. PMID:25578955

  18. Stress adaptation in foodborne pathogens.

    PubMed

    Begley, Máire; Hill, Colin

    2015-01-01

    Foodborne bacterial pathogens encounter many environmental insults or stresses during food production, processing, storage, distribution, and preparation. However, these pathogens can sense changes in their surroundings and can respond by altering gene expression. A protective response may follow that increases tolerance to one or more stresses. This phenomenon is referred to as stress adaptation and has been shown to aid in the survival of pathogens in food products and in the food processing environment. Furthermore, stress adaptation may alter the virulence properties of pathogens and can contribute to survival in vivo during infection. Elucidating the molecular mechanisms underlying stress adaptation in bacterial food pathogens is essential for the development and implementation of more effective control measures and will permit the design of optimal processing regimes that combine maximum safety with consumer demands for more fresh-like, minimally processed foods. PMID:25665171

  19. How Do Filamentous Pathogens Deliver Effector Proteins into Plant Cells?

    PubMed Central

    Petre, Benjamin; Kamoun, Sophien

    2014-01-01

    Fungal and oomycete plant parasites are among the most devastating pathogens of food crops. These microbes secrete effector proteins inside plant cells to manipulate host processes and facilitate colonization. How these effectors reach the host cytoplasm remains an unclear and debated area of plant research. In this article, we examine recent conflicting findings that have generated discussion in the field. We also highlight promising approaches based on studies of both parasite and host during infection. Ultimately, this knowledge may inform future broad spectrum strategies for protecting crops from such pathogens. PMID:24586116

  20. Interaction between pathogenic proteins in neurodegenerative disorders

    PubMed Central

    Jellinger, Kurt A; Popescu, BO

    2012-01-01

    Abstract The misfolding and progressive aggregation of specific proteins in selective regions of the nervous system is a seminal occurrence in many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic and experimental differences, increasing evidence indicates considerable overlap between synucleinopathies, tauopathies and other protein-misfolding diseases. Inclusions, often characteristic hallmarks of these disorders, suggest interactions of pathological proteins enganging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Alzheimer, Parkinson, Huntington and prion diseases, have confirmed correlations/overlaps between these and other neurodegenerative disorders. Emerging evidence, in addition to synergistic effects of tau protein, amyloid-?, ?-synuclein and other pathologic proteins, suggests that prion-like induction and spreading, involving secreted proteins, are major pathogenic mechanisms in various neurodegenerative diseases, depending on genetic backgrounds and environmental factors. The elucidation of the basic molecular mechanisms underlying the interaction and spreading of pathogenic proteins, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, is a major challenge for modern neuroscience, to provide a deeper insight into their pathogenesis as a basis of effective diagnosis and treatment. PMID:22176890

  1. Bacteria: More Than Pathogens

    NSDL National Science Digital Library

    Wassenaar, Trudy M.

    This ActionBioscience lesson plan has students explore the many roles of bacteria, harmful and beneficial. A detailed article written for ActionBioscience by a microbiologist provides background information, which is followed by discussion questions and educational activities designed for middle school to undergraduate biology courses. The Web site also provides carefully selected links for further exploring the topic, including useful sites for student research projects.

  2. Pathogen virulence of Phytophthora infestans: from gene to functional genomics.

    PubMed

    Sanju, Suman; Thakur, Aditi; Siddappa, Sundresha; Sreevathsa, Rohini; Srivastava, Nidhi; Shukla, Pradeep; Singh, B P

    2013-04-01

    The oomycete, Phytophthora infestans, is one of the most important plant pathogens worldwide. Much of the pathogenic success of P. infestans, the potato late blight agent, relies on its ability to generate large amounts of sporangia from mycelia, which release zoospores that encyst and form infection structures. Until recently, little was known about the molecular basis of oomycete pathogenicity by the avirulence molecules that are perceived by host defenses. To understand the molecular mechanisms interplay in the pathogen and host interactions, knowledge of the genome structure was most important, which is available now after genome sequencing. The mechanism of biotrophic interaction between potato and P. infestans could be determined by understanding the effector biology of the pathogen, which is until now poorly understood. The recent availability of oomycete genome will help in understanding of the signal transduction pathways followed by apoplastic and cytoplasmic effectors for translocation into host cell. Finally based on genomics, novel strategies could be developed for effective management of the crop losses due to the late blight disease. PMID:24431484

  3. Pathogens in Dairy Farming: Source Characterization and Groundwater Impacts

    NASA Astrophysics Data System (ADS)

    Atwill, E. R.; Watanabe, N.; Li, X.; Hou, L.; Harter, T.; Bergamaschi, B.

    2007-12-01

    Intense animal husbandry is of growing concern as a potential contamination source of enteric pathogens as well as antibiotics. To assess the public health risk from pathogens and their hydrologic pathways, we hypothesize that the animal farm is not a homogeneous diffuse source, but that pathogen loading to the soil and, therefore, to groundwater varies significantly between the various management units of a farm. A dairy farm, for example, may include an area with calf hutches, corrals for heifers of various ages, freestalls and exercise yards for milking cows, separate freestalls for dry cows, a hospital barn, a yard for collection of solid manure, a liquid manure storage lagoon, and fields receiving various amounts of liquid and solid manure. Pathogen shedding and, hence, therapeutic and preventive pharmaceutical treatments vary between these management units. We are implementing a field reconnaissance program to determine the occurrence of three different pathogens ( E. coli, Salmonella, Campylobacter) and one indicator organism ( Enterococcus) at the ground-surface and in shallow groundwater of seven different management units on each of two farms, and in each of four seasons (spring/dry season, summer/irrigation season, fall/dry season, winter/rainy season). Initial results indicate that significant differences exist in the occurrence of these pathogens between management units and between organisms. These differences are weakly reflected in their occurrence in groundwater, despite the similarity of the shallow geologic environment across these sites. Our results indicate the importance of differentiating sources within a dairy farm and the importance of understanding subsurface transport processes for these pathogens.

  4. Signaling pathways regulating innate immune responses in shrimp.

    PubMed

    Li, Fuhua; Xiang, Jianhai

    2013-04-01

    The first line of defense against microbial infections in animals is innate immune response which triggers diverse humoral and cellular activities via signal transduction pathways. Toll, IMD and JAK/STAT pathways are regarded as the main pathways regulating the immune response of invertebrates. This paper reviews the main progress of the investigation on the immune response to pathogen's infection in shrimp and supposes that these three signal pathways exist in shrimp. Most of the components (proteins or genes) involved in Toll pathway of Drosophila have been cloned also in shrimp which suggested the existence of Toll pathway in shrimp. The data update shows that the Toll pathway of shrimp is responsive not only to Gram-positive bacteria, Gram-negative bacteria, but also to WSSV. Challenge of WSSV can lead to the variation of transcription level of all identified components in shrimp Toll pathway, which supported that Toll pathway in shrimp played important roles during WSSV infection. Two major homologs to the components of IMD pathway of Drosophila, IMD and Relish, have been identified in shrimp, which indicated that IMD pathway should be existed in shrimp and might play important roles in regulating the immune response of shrimp to bacteria and virus infection. Relish in IMD pathway and dorsal in Toll pathway of shrimp were both involved in the immune response of shrimp to bacteria and virus infection, which implied that these two pathways are not completely separated during the immune response of shrimp. The transcription of STAT in shrimp was modulated after WSSV infection, which suggested that a putative JAK/STAT pathway might exist in shrimp and be very important to virus infection. Study on the signaling pathway regulating the immune response in shrimp could help us to understand the innate immune system, and would provide instructions to shrimp disease control. Obviously, to get more clear ideas about the innate immunological pathways in shrimp, more solid functional studies should be done in the future. PMID:22967763

  5. Antimicrobial protein protects grapevines from pathogen

    E-print Network

    - 1 - Antimicrobial protein protects grapevines from pathogen February 21, 2012 Antimicrobial protein protects grapevines from pathogen Engineered grapevines produce a hybrid antimicrobial protein any pathogen, the major problem is drug resistance," said Goutam Gupta, the corresponding author

  6. Exposure Control Plan Bloodborne Pathogen Program

    E-print Network

    Natelson, Douglas

    Exposure Control Plan Bloodborne Pathogen Program 1. Introduction 2. Occupational Exposure Bloodborne Pathogen Program 1. INTRODUCTION OSHA defines occupational exposure as reasonably anticipated skin set forth in the Bloodborne Pathogens (BBP) Standard are necessary to provide protection to employees

  7. Molecular Responses to Aphid Feeding in Arabidopsis in Relation to Plant Defense Pathways

    Microsoft Academic Search

    Patrick J. Moran; Gary A. Thompson

    2001-01-01

    Little is known about molecular responses in plants to phloem feeding by insects. The induction of genes associated with wound and pathogen response pathways was investigated following green peach aphid (Myzus persicae) feeding on Arabidopsis. Aphid feeding on rosette leaves induced transcription of two genes associated with salicylic acid (SA)- dependent responses to pathogens (PR-1 and BGL2) 10- and 23-fold,

  8. Adhesion by pathogenic corynebacteria.

    PubMed

    Rogers, Elizabeth A; Das, Asis; Ton-That, Hung

    2011-01-01

    Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and SpaH-type pili. Similar to other types, the prototype SpaA pilus consists of SpaA forming the pilus shaft and two minor pilins SpaB and SpaC located at the base and at the tip, respectively. The minor pilins SpaB/SpaC are critical for bacterial binding to human pharyngeal cells, and thus represent the major adhesins of corynebacteria. Like pili of many other gram-positive microbes, the assembly of corynebacterial pili occurs by a two-step mechanism, whereby pilins are covalently polymerized by a transpeptidase enzyme named pilin-specific sortase and the generated pilus polymer is subsequently anchored to the cell wall peptidoglycan via the base pilin by the housekeeping sortase or a non-polymerizing sortase. This chapter reviews the current knowledge of corynebacterial adhesion, with a specific focus on pilus structures, their assembly, and the mechanism of adhesion mediated by pili. PMID:21557059

  9. Transient virulence of emerging pathogens

    PubMed Central

    Bolker, Benjamin M.; Nanda, Arjun; Shah, Dharmini

    2010-01-01

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution. PMID:19864267

  10. Finding the Sweet Spot: How Human Fungal Pathogens Acquire and Turn the Sugar Inositol against Their Hosts

    PubMed Central

    2015-01-01

    ABSTRACT Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio 5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species—obligate fungal pathogens that remain unculturable in vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth in vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens. PMID:25736882

  11. Finding the Sweet Spot: How Human Fungal Pathogens Acquire and Turn the Sugar Inositol against Their Hosts.

    PubMed

    Xue, Chaoyang

    2015-01-01

    Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio 5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species-obligate fungal pathogens that remain unculturable in vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth in vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens. PMID:25736882

  12. MINI REVIEW ARTICLE published: 04 April 2014

    E-print Network

    Hirt, Heribert

    colonization. It was recently shown that plants detect Salmonella pathogen-associated molecular patterns (PAMPs that a strategy of Salmonella is to escape plant detection by mutating PAMP motifs. Another strategy may relyMINI REVIEW ARTICLE published: 04 April 2014 doi: 10.3389/fmicb.2014.00141 Salmonella enterica

  13. RESEARCH ARTICLE Insecticidal Suppression of Asian Citrus

    E-print Network

    Florida, University of

    RESEARCH ARTICLE Insecticidal Suppression of Asian Citrus Psyllid Diaphorina citri (Hemiptera@ufl.edu Abstract Diaphorina citri vectors pathogens that cause `huanglongbing' or citrus greening disease which poses a serious threat to citrus production worldwide. Vector suppression is critical to reduce disease

  14. RESEARCH ARTICLE Nucleotide Sequence of Yellow Fever

    E-print Network

    Eddy, Sean

    RESEARCH ARTICLE Nucleotide Sequence of Yellow Fever Virus: Implications for Flavivirus Gene related human or veterinary pathogens causing many serious illness- es, including dengue fever, Japanese, and yellow fever (1). Most fever was spread by ship to ports as far north as Boston and as far east as En

  15. Host Pathogen Relations: Exploring Animal Models for Fungal Pathogens

    PubMed Central

    Harwood, Catherine G.; Rao, Reeta P.

    2014-01-01

    Pathogenic fungi cause superficial infections but pose a significant public health risk when infections spread to deeper tissues, such as the lung. Within the last three decades, fungi have been identified as the leading cause of nosocomial infections making them the focus of research. This review outlines the model systems such as the mouse, zebrafish larvae, flies, and nematodes, as well as ex vivo and in vitro systems available to study common fungal pathogens. PMID:25438011

  16. Pathogenic Mechanisms of Pulmonary Arterial Hypertension

    PubMed Central

    Chan, Stephen Y.; Loscalzo, Joseph

    2008-01-01

    Pulmonary arterial hypertension (PAH)1 is a complex disease that causes significant morbidity and mortality and is clinically characterized by an increase in pulmonary vascular resistance. The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction. Development of PAH involves the complex interaction of multiple vascular effectors at all anatomic levels of the arterial wall. Subsequent vasoconstriction, thrombosis, and inflammation ensue, leading to vessel wall remodeling and cellular hyperproliferation as the hallmarks of severe disease. These processes are influenced by genetic predisposition as well as diverse endogenous and exogenous stimuli. Recent studies have provided a glimpse at certain molecular pathways that contribute to pathogenesis; these have led to the identification of attractive targets for therapeutic intervention. We will review our current understanding of the mechanistic underpinnings of the genetic and exogenous/acquired triggers of PAH. The resulting imbalance of vascular effectors provoking pathogenic vascular changes will also be discussed, with an emphasis on common and overarching regulatory pathways that may relate to the primary triggers of disease. The current conceptual framework should allow for future studies to refine our understanding of the molecular pathogenesis of PAH and improve the therapeutic regimen for this disease. PMID:17950310

  17. Article URL

    E-print Network

    Siddesh Shambhu; Kevin Phillips; Siddesh Shambhu; Kevin Phillips; Kate Guthrie

    2009-01-01

    This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. A levonorgestrel-releasing intrauterine system embedded in the omentum in a woman with abdominal pain: a case report

  18. SIGNAL TRANSDUCTION: Nuclear Fusion of Signaling Pathways

    NSDL National Science Digital Library

    Ralf Janknecht (Mayo Clinic; Department of Biochemistry and Molecular Biology)

    1999-04-16

    Access to the article is free, however registration and sign-in are required. There is often crosstalk between signal transduction pathways activated by different cytokines. In this issue, Nakashima and colleagues report on one way in which signaling pathways communicate. They show that the signaling pathways for two cytokines (LIF and BMP2), which are necessary for astrocyte differentiation, can interact synergistically through the binding of their transcription factor targets (STAT3 and Smad1, respectively) to a common transcriptional coactivator molecule called p300.

  19. The Evolution of the Wnt Pathway

    PubMed Central

    Holstein, Thomas W.

    2012-01-01

    Wnt genes are important regulators of embryogenesis and cell differentiation in vertebrates and insects. New data revealed by comparative genomics have now shown that members of the Wnt signaling pathway can be found in all clades of metazoans, but not in fungi, plants, or unicellular eukaryotes. This article focuses on new data from recent genomic analyses of several basal metazoan organisms, providing evidence that the Wnt pathway was a primordial signaling pathway during evolution. The formation of a Wnt signaling center at the site of gastrulation was instrumental for the formation of a primary, anterior–posterior body axis, which can be traced throughout animal evolution. PMID:22751150

  20. Interactive Fly: Developmental Pathways

    NSDL National Science Digital Library

    PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

    2006-12-11

    this site describes evolutionarily conserved developmental pathways. The pathways are named according to the processes they govern, and not by the names of the genes involved: for example, "lateral inhibition" rather than "the Notch pathway." Inevitably, there will be cases where the function is less well understood: hence, "the Wingless pathway."

  1. Volatile Metabolites of Pathogens: A Systematic Review

    PubMed Central

    Bos, Lieuwe D. J.; Sterk, Peter J.; Schultz, Marcus J.

    2013-01-01

    Ideally, invading bacteria are detected as early as possible in critically ill patients: the strain of morbific pathogens is identified rapidly, and antimicrobial sensitivity is known well before the start of new antimicrobial therapy. Bacteria have a distinct metabolism, part of which results in the production of bacteria-specific volatile organic compounds (VOCs), which might be used for diagnostic purposes. Volatile metabolites can be investigated directly in exhaled air, allowing for noninvasive monitoring. The aim of this review is to provide an overview of VOCs produced by the six most abundant and pathogenic bacteria in sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Such VOCs could be used as biological markers in the diagnostic approach of critically ill patients. A systematic review of existing literature revealed 31 articles. All six bacteria of interest produce isopentanol, formaldehyde, methyl mercaptan, and trimethylamine. Since humans do not produce these VOCs, they could serve as biological markers for presence of these pathogens. The following volatile biomarkers were found for identification of specific strains: isovaleric acid and 2-methyl-butanal for Staphylococcus aureus; 1-undecene, 2,4-dimethyl-1-heptane, 2-butanone, 4-methyl-quinazoline, hydrogen cyanide, and methyl thiocyanide for Pseudomonas aeruginosa; and methanol, pentanol, ethyl acetate, and indole for Escherichia coli. Notably, several factors that may effect VOC production were not controlled for, including used culture media, bacterial growth phase, and genomic variation within bacterial strains. In conclusion, VOCs produced by bacteria may serve as biological markers for their presence. Goal-targeted studies should be performed to identify potential sets of volatile biological markers and evaluate the diagnostic accuracy of these markers in critically ill patients. PMID:23675295

  2. Laminate article

    DOEpatents

    Williams, Robert K. (Knoxville, TN); Paranthaman, Mariappan (Knoxville, TN); Chirayil, Thomas G. (Knoxville, TN); Lee, Dominic F. (Knoxville, TN); Goyal, Amit (Knoxville, TN); Feenstra, Roeland (Knoxville, TN)

    2002-01-01

    A laminate article comprises a substrate and a biaxially textured (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer over the substrate, wherein 0article can include a layer of YBCO over the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer. A layer of CeO.sub.2 between the YBCO layer and the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer can also be include. Further included can be a layer of YSZ between the CeO.sub.2 layer and the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer. The substrate can be a biaxially textured metal, such as nickel. A method of forming the laminate article is also disclosed.

  3. The Aedes aegypti Toll Pathway Controls Dengue Virus Infection

    Microsoft Academic Search

    Zhiyong Xi; Jose L. Ramirez; George Dimopoulos

    2008-01-01

    Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of

  4. Food Microbial Pathogen Detection and Analysis Using DNA Microarray Technologies

    PubMed Central

    Herold, Keith E.

    2008-01-01

    Abstract Culture-based methods used for microbial detection and identification are simple to use, relatively inexpensive, and sensitive. However, culture-based methods are too time-consuming for high-throughput testing and too tedious for analysis of samples with multiple organisms and provide little clinical information regarding the pathogen (e.g., antibiotic resistance genes, virulence factors, or strain subtype). DNA-based methods, such as polymerase chain reaction (PCR), overcome some these limitations since they are generally faster and can provide more information than culture-based methods. One limitation of traditional PCR-based methods is that they are normally limited to the analysis of a single pathogen, a small group of related pathogens, or a small number of relevant genes. Microarray technology enables a significant expansion of the capability of DNA-based methods in terms of the number of DNA sequences that can be analyzed simultaneously, enabling molecular identification and characterization of multiple pathogens and many genes in a single array assay. Microarray analysis of microbial pathogens has potential uses in research, food safety, medical, agricultural, regulatory, public health, and industrial settings. In this article, we describe the main technical elements of microarray technology and the application and potential use of DNA microarrays for food microbial analysis. PMID:18673074

  5. Plants, plant pathogens, and microgravity--a deadly trio

    NASA Technical Reports Server (NTRS)

    Leach, J. E.; Ryba-White, M.; Sun, Q.; Wu, C. J.; Hilaire, E.; Gartner, C.; Nedukha, O.; Kordyum, E.; Keck, M.; Leung, H.; Guikema, J. A.

    2001-01-01

    Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment.

  6. PathogenMip assay: a multiplex pathogen detection assay.

    PubMed

    Akhras, Michael S; Thiyagarajan, Sreedevi; Villablanca, Andrea C; Davis, Ronald W; Nyrén, Pål; Pourmand, Nader

    2007-01-01

    The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe. PMID:17311101

  7. Microbial Exposure Assessment of Waterborne Pathogens

    Microsoft Academic Search

    Rory Coffey; Enda Cummins; Martin Cormican; Vincent O Flaherty; Stephen Kelly

    2007-01-01

    The large number of waterborne illnesses in Ireland and worldwide has highlighted the need to enhance strategies that minimize human exposure to pathogens in drinking water supplies. Waterborne pathogens of public concern together with relevant national and international legislation are reviewed in this study. Cryptosporidium species and pathogenic Escherichia coli are among pathogens of primary concern. The organisms originate from

  8. Anopheles NF-?B -regulated splicing factors direct pathogen-specific repertoires of the hypervariable pattern recognition receptor AgDscam

    PubMed Central

    Dong, Yuemei; Cirimotich, Chris M; Pike, Andrew; Chandra, Ramesh; Dimopoulos, George

    2012-01-01

    Insects rely on innate immune responses controlled by the immune deficiency (IMD), Toll and other immune signaling pathways, to combat infection by a broad spectrum of pathogens. These pathways signal to downstream NF-?B family transcription factors which control specific anti-pathogen action via direct transcriptional control of immune effectors, hematopoiesis and melanization. Here we show that in the Anopheles malaria vector, IMD and Toll pathways mediate species-specific defenses against Plasmodium and bacteria through the transcriptional regulation of splicing factors Caper and IRSF1 that, in turn, determine the production of pathogen-specific splice variant repertoires of the hypervariable pattern recognition receptor AgDscam. This mechanism represents an additional level of immune response regulation that may provide a previously unrecognized level of plasticity to the insect immune pathway-regulated anti-pathogen defenses. PMID:23084919

  9. Pathogen evolution and the immunological niche

    PubMed Central

    Cobey, Sarah

    2014-01-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible–infected–recovered (SIR) model. However, there is growing evidence that the complexity of many host–pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

  10. Pathogen evolution and the immunological niche.

    PubMed

    Cobey, Sarah

    2014-07-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

  11. Waterborne protozoan pathogens.

    PubMed Central

    Marshall, M M; Naumovitz, D; Ortega, Y; Sterling, C R

    1997-01-01

    Protozoan parasites were the most frequently identified etiologic agents in waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli, and the microsporidia are reviewed. For each parasite, the review includes history, life cycle, incidence, symptoms, and therapy. Clinical detection methods are compared, and emerging technologies are discussed. Information on the association of these parasites with waterborne outbreaks is reviewed. Current information on protozoan parasites identified as etiological agents in waterborne outbreaks is discussed. Water industry issues related to recent disease outbreaks are examined in the context of water quality testing regulations for G. lamblia and those proposed for C. parvum. The review identifies the limitations of the American Society of Testing and Materials water-testing method for these parasites. An overview of federal regulations affecting the water industry and laboratories that test for water quality is also provided. The article highlights the importance of the clinical laboratory as a frontline defense for the detection of infectious organisms. The review points to the need for clinical laboratories, physicians, and public health personnel to cooperatively plan and assess the challenge of meeting this potential public health threat. PMID:8993859

  12. Toll-like receptors. II. Distribution and pathways involved in TLR signalling.

    PubMed

    Sandor, F; Buc, M

    2005-01-01

    The innate immune system senses invading microorganisms by a phylogenetically conserved family of proteins--TLRs. They are expressed in several types of cells that represent a route of entry of pathogens into the host organism and that can contribute to protection against infection. Except for cells of the immune system, TLRs are present in epithelial cells of the skin, respiratory, intestinal, and genitourinary tracts that form the first protective barrier to invading pathogens. Polarized regulation of TLR expression in epithelial cells explains why pathogenic but not commensal bacteria elicit inflammatory responses. TLR-induced intracellular signalling pathways show remarkable complexity: apart from a common signalling pathway, additional signalling pathways specific for each of the TLRs are responsible for a fine tuning of the immune response, thus securing effective pathogen-directed biological responses. PMID:16419614

  13. Developmental pathways to antisocial behavior: the delayed-onset pathway in girls.

    PubMed

    Silverthorn, P; Frick, P J

    1999-01-01

    Recent research has suggested that there are two distinct trajectories for the development of antisocial behavior in boys: a childhood-onset pathway and an adolescent-onset pathway. After reviewing the limited available research on antisocial girls, we propose that this influential method of conceptualizing the development of severe antisocial behavior may not apply to girls without some important modifications. Antisocial girls appear to show many of the correlates that have been associated with the childhood-onset pathway in boys, and they tend to show impaired adult adjustment, which is also similar to boys in the childhood-onset pathway. However, antisocial girls typically show an adolescent-onset to their antisocial behavior. We have proposed that these girls show a third developmental pathway which we have labeled the "delayed-onset" pathway. This model rests on the assumption that many of the putative pathogenic mechanisms that contribute to the development of antisocial behavior in girls, such as cognitive and neuropsychological deficits, a dysfunctional family environment, and/or the presence of a callous and unemotional interpersonal style, may be present in childhood, but they do not lead to severe and overt antisocial behavior until adolescence. Therefore, we propose that the delayed-onset pathway for girls is analogous to the childhood-onset pathway in boys and that there is no analogous pathway in girls to the adolescent-onset pathway in boys. Although this model clearly needs to be tested in future research, it highlights the need to test the applicability of current theoretical models for explaining the development of antisocial behavior in girls. PMID:10208358

  14. Sex-Dependent Resistance to the Pathogenic Fungus Cryptococcus neoformans

    PubMed Central

    van den Berg, Maaike C. W.; Woerlee, Jessica Z.; Ma, Hansong; May, Robin C.

    2006-01-01

    Sex differences occur in most species and affect a variety of biological traits including morphology, behavior, and life history. The nematode Caenorhabditis elegans exists as a population of self-fertile hermaphrodites with occasional males, which differ anatomically and behaviorally from hermaphrodites. Here we show that male C. elegans also differ from hermaphrodites in their susceptibility to a fungal pathogen, Cryptococcus neoformans. Wild-type males show greater resistance than hermaphrodite animals to killing by this pathogen and this resistance can be induced in hermaphrodite animals by inappropriate activation of the male sex-determination pathway. Resistance is molecularly determined, rather than resulting from behavioral changes or reproductive differences, and requires the activity of the stress-response transcription factor DAF-16. Finally, we demonstrate that resistance to C. neoformans correlates broadly with longevity within the Caenorhabditis genus. Our results hint at an overlap between the pathways controlling immunity and longevity and raise the possibility that differential regulation of these pathways may contribute to sex-dependent and species-dependent variation. PMID:16582430

  15. Edinburgh Research Explorer Highly pathogenic or low pathogenic avian influenza virus

    E-print Network

    Millar, Andrew J.

    Edinburgh Research Explorer Highly pathogenic or low pathogenic avian influenza virus subtype H7N1 pathogenic avian influenza virus subtype H7N1 infection in chicken lungs: small differences in general acute. 2014 #12;RESEARCH Open Access Highly pathogenic or low pathogenic avian influenza virus subtype H7N1

  16. Pathways to Childlessness: A Life Course Perspective

    ERIC Educational Resources Information Center

    Hagestad, Gunhild O.; Call, Vaughn R. A.

    2007-01-01

    In this article life history data from the U.S. National Survey of Families and Households (NSFH), and the Dutch survey on Older Adults' Living Arrangements and Social Networks (NESTOR-LSN) are used to shed light on the various pathways leading to and associated with childlessness, and the proportions of men and women who have followed a…

  17. Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

    PubMed Central

    Bartell, Jennifer A.; Yen, Phillip; Varga, John J.; Goldberg, Joanna B.

    2014-01-01

    Burkholderia cenocepacia and Burkholderia multivorans are opportunistic drug-resistant pathogens that account for the majority of Burkholderia cepacia complex infections in cystic fibrosis patients and also infect other immunocompromised individuals. While they share similar genetic compositions, B. cenocepacia and B. multivorans exhibit important differences in pathogenesis. We have developed reconciled genome-scale metabolic network reconstructions of B. cenocepacia J2315 and B. multivorans ATCC 17616 in parallel (designated iPY1537 and iJB1411, respectively) to compare metabolic abilities and contextualize genetic differences between species. The reconstructions capture the metabolic functions of the two species and give insight into similarities and differences in their virulence and growth capabilities. The two reconstructions have 1,437 reactions in common, and iPY1537 and iJB1411 have 67 and 36 metabolic reactions unique to each, respectively. After curating the extensive reservoir of metabolic genes in Burkholderia, we identified 6 genes essential to growth that are unique to iPY1513 and 13 genes uniquely essential to iJB1411. The reconstructions were refined and validated by comparing in silico growth predictions to in vitro growth capabilities of B. cenocepacia J2315, B. cenocepacia K56-2, and B. multivorans ATCC 17616 on 104 carbon sources. Overall, we identified functional pathways that indicate B. cenocepacia can produce a wider array of virulence factors compared to B. multivorans, which supports the clinical observation that B. cenocepacia is more virulent than B. multivorans. The reconciled reconstructions provide a framework for generating and testing hypotheses on the metabolic and virulence capabilities of these two related emerging pathogens. PMID:24163337

  18. Modifying lignin to improve bioenergy feedstocks: strengthening the barrier against pathogens?†

    PubMed Central

    Sattler, Scott E.; Funnell-Harris, Deanna L.

    2013-01-01

    Lignin is a ubiquitous polymer present in cell walls of all vascular plants, where it rigidifies and strengthens the cell wall structure through covalent cross-linkages to cell wall polysaccharides. The presence of lignin makes the cell wall recalcitrant to conversion into fermentable sugars for bioenergy uses. Therefore, reducing lignin content and modifying its linkages have become major targets for bioenergy feedstock development through either biotechnology or traditional plant breeding. In addition, lignin synthesis has long been implicated as an important plant defense mechanism against pathogens, because lignin synthesis is often induced at the site of pathogen attack. This article explores the impact of lignin modifications on the susceptibility of a range of plant species to their associated pathogens, and the implications for development of feedstocks for the second-generation biofuels industry. Surprisingly, there are some instances where plants modified in lignin synthesis may display increased resistance to associated pathogens, which is explored in this article. PMID:23577013

  19. Gating by Cyclic AMP: Expanded Role for an Old Signaling Pathway

    NSDL National Science Digital Library

    Ravi Iyengar (City University of New York; Department of Pharmacology, Mount Sinai School of Medicine)

    1996-01-26

    Access to the article is free, however registration and sign-in are required. The intracellular signal transduction pathway that utilizes cyclic AMP as a key messenger was the first such pathway to be described and has served as a model for many other transducing systems. Now Iyengar illustrates how this classic pathway has yet another function--in a number of different biological systems, the cyclic AMP pathway appears to gate (either negatively or positively) other signal transduction pathways.

  20. Human pathogenic bacteria, fungi, and viruses in Drosophila

    PubMed Central

    Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

    2014-01-01

    Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila–microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection. PMID:24398387

  1. Evolution of pathogenicity and sexual reproduction in eight Candida genomes

    PubMed Central

    Butler, Geraldine; Rasmussen, Matthew D.; Lin, Michael F.; Santos, Manuel A.S.; Sakthikumar, Sharadha; Munro, Carol A.; Rheinbay, Esther; Grabherr, Manfred; Forche, Anja; Reedy, Jennifer L.; Agrafioti, Ino; Arnaud, Martha B.; Bates, Steven; Brown, Alistair J.P.; Brunke, Sascha; Costanzo, Maria C.; Fitzpatrick, David A.; de Groot, Piet W. J.; Harris, David; Hoyer, Lois L.; Hube, Bernhard; Klis, Frans M.; Kodira, Chinnappa; Lennard, Nicola; Logue, Mary E.; Martin, Ronny; Neiman, Aaron M.; Nikolaou, Elissavet; Quail, Michael A.; Quinn, Janet; Santos, Maria C.; Schmitzberger, Florian F.; Sherlock, Gavin; Shah, Prachi; Silverstein, Kevin; Skrzypek, Marek S.; Soll, David; Staggs, Rodney; Stansfield, Ian; Stumpf, Michael P H; Sudbery, Peter E.; Thyagarajan, Srikantha; Zeng, Qiandong; Berman, Judith; Berriman, Matthew; Heitman, Joseph; Gow, Neil A. R.; Lorenz, Michael C.; Birren, Bruce W.; Kellis, Manolis; Cuomo, Christina A.

    2009-01-01

    Candida species are the most common cause of opportunistic fungal infection worldwide. We report the genome sequences of six Candida species and compare these and related pathogens and nonpathogens. There are significant expansions of cell wall, secreted, and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the Mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/alpha2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine to serine genetic code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the C. albicans gene catalog, identifying many new genes. PMID:19465905

  2. Hepcidin Induction by Pathogens and Pathogen-Derived Molecules Is Strongly Dependent on Interleukin-6

    PubMed Central

    Rodriguez, Richard; Jung, Chun-Ling; Gabayan, Victoria; Deng, Jane C.; Ganz, Tomas; Nemeth, Elizabeta

    2014-01-01

    Hepcidin, the iron-regulatory hormone, is increased during infection or inflammation, causing hypoferremia. This response is thought to be a host defense mechanism that restricts iron availability to invading pathogens. It is not known if hepcidin is differentially induced by bacterial versus viral infections, whether the stimulation of pattern recognition receptors directly regulates hepcidin transcription, or which of the proposed signaling pathways are essential for hepcidin increase during infection. We analyzed hepcidin induction and its dependence on interleukin-6 (IL-6) in response to common bacterial or viral infections in mice or in response to a panel of pathogen-derived molecules (PAMPs) in mice and human primary hepatocytes. In wild-type (WT) mice, hepcidin mRNA was induced several hundred-fold both by a bacterial (Streptococcus pneumoniae) and a viral infection (influenza virus PR8) within 2 to 5 days. Treatment of mice and human primary hepatocytes with most Toll-like receptor ligands increased hepcidin mRNA within 6 h. Hepcidin induction by microbial stimuli was IL-6 dependent. IL-6 knockout mice failed to increase hepcidin in response to S. pneumoniae or influenza infection and had greatly diminished hepcidin response to PAMPs. In vitro, hepcidin induction by PAMPs in primary human hepatocytes was abolished by the addition of neutralizing IL-6 antibodies. Our results support the key role of IL-6 in hepcidin regulation in response to a variety of infectious and inflammatory stimuli. PMID:24478088

  3. A Relational Database for the Discovery of Genes Encoding Amino Acid Biosynthetic Enzymes in Pathogenic Fungi

    PubMed Central

    Giles, Peter F.; Soanes, Darren M.

    2003-01-01

    Fungal phytopathogens continue to cause major economic impact, either directly, through crop losses, or due to the costs of fungicide application. Attempts to understand these organisms are hampered by a lack of fungal genome sequence data. A need exists, however, to develop specific bioinformatics tools to collate and analyse the sequence data that currently is available. A web-accessible gene discovery database (http://cogeme.ex.ac.uk/biosynthesis.html) was developed as a demonstration tool for the analysis of metabolic and signal transduction pathways in pathogenic fungi using incomplete gene inventories. Using Bayesian probability to analyse the currently available gene information from pathogenic fungi, we provide evidence that the obligate pathogen Blumeria graminis possesses all amino acid biosynthetic pathways found in free-living fungi, such as Saccharomyces cerevisiae. Phylogenetic analysis was also used to deduce a gene history of succinate-semialdehyde dehydrogenase, an enzyme in the glutamate and lysine biosynthesis pathways. The database provides a tool and methodology to researchers to direct experimentation towards predicting pathway conservation in pathogenic microorganisms. PMID:18629094

  4. Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction

    Microsoft Academic Search

    Anu Raghunathan; Jennifer Reed; Sookil Shin; Bernhard Palsson; Simon Daefler

    2009-01-01

    BACKGROUND: Infections with Salmonella cause significant morbidity and mortality worldwide. Replication of Salmonella typhimurium inside its host cell is a model system for studying the pathogenesis of intracellular bacterial infections. Genome-scale modeling of bacterial metabolic networks provides a powerful tool to identify and analyze pathways required for successful intracellular replication during host-pathogen interaction. RESULTS: We have developed and validated a

  5. Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans

    PubMed Central

    Kim, Hanhae; Jung, Kwang-Woo; Maeng, Shinae; Chen, Ying-Lien; Shin, Junha; Shim, Jung Eun; Hwang, Sohyun; Janbon, Guilhem; Kim, Taeyup; Heitman, Joseph; Bahn, Yong-Sun; Lee, Insuk

    2015-01-01

    Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative. The analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phenotypes but with limited efficiency. Here, we present a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the coding genome and provides an efficient intermediary between functional genomics data and reverse-genetics resources for the genetic dissection of C. neoformans phenotypes. CryptoNet is the first genome-scale co-functional network for any fungal pathogen. CryptoNet effectively identified novel genes for pathogenicity and drug resistance using guilt-by-association and context-associated hub algorithms. CryptoNet is also the first genome-scale co-functional network for fungi in the basidiomycota phylum, as Saccharomyces cerevisiae belongs to the ascomycota phylum. CryptoNet may therefore provide insights into pathway evolution between two distinct phyla of the fungal kingdom. The CryptoNet web server (www.inetbio.org/cryptonet) is a public resource that provides an interactive environment of network-assisted predictive genetics for C. neoformans. PMID:25739925

  6. Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans.

    PubMed

    Kim, Hanhae; Jung, Kwang-Woo; Maeng, Shinae; Chen, Ying-Lien; Shin, Junha; Shim, Jung Eun; Hwang, Sohyun; Janbon, Guilhem; Kim, Taeyup; Heitman, Joseph; Bahn, Yong-Sun; Lee, Insuk

    2015-01-01

    Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative. The analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phenotypes but with limited efficiency. Here, we present a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the coding genome and provides an efficient intermediary between functional genomics data and reverse-genetics resources for the genetic dissection of C. neoformans phenotypes. CryptoNet is the first genome-scale co-functional network for any fungal pathogen. CryptoNet effectively identified novel genes for pathogenicity and drug resistance using guilt-by-association and context-associated hub algorithms. CryptoNet is also the first genome-scale co-functional network for fungi in the basidiomycota phylum, as Saccharomyces cerevisiae belongs to the ascomycota phylum. CryptoNet may therefore provide insights into pathway evolution between two distinct phyla of the fungal kingdom. The CryptoNet web server (www.inetbio.org/cryptonet) is a public resource that provides an interactive environment of network-assisted predictive genetics for C. neoformans. PMID:25739925

  7. Proteomics of Plant Pathogenic Fungi

    PubMed Central

    González-Fernández, Raquel; Prats, Elena; Jorrín-Novo, Jesús V.

    2010-01-01

    Plant pathogenic fungi cause important yield losses in crops. In order to develop efficient and environmental friendly crop protection strategies, molecular studies of the fungal biological cycle, virulence factors, and interaction with its host are necessary. For that reason, several approaches have been performed using both classical genetic, cell biology, and biochemistry and the modern, holistic, and high-throughput, omic techniques. This work briefly overviews the tools available for studying Plant Pathogenic Fungi and is amply focused on MS-based Proteomics analysis, based on original papers published up to December 2009. At a methodological level, different steps in a proteomic workflow experiment are discussed. Separate sections are devoted to fungal descriptive (intracellular, subcellular, extracellular) and differential expression proteomics and interactomics. From the work published we can conclude that Proteomics, in combination with other techniques, constitutes a powerful tool for providing important information about pathogenicity and virulence factors, thus opening up new possibilities for crop disease diagnosis and crop protection. PMID:20589070

  8. Pathogens and the Placental Fortress

    PubMed Central

    Robbins, Jennifer R.

    2011-01-01

    Summary Placental infections are major causes of maternal and fetal disease. This review introduces a new paradigm for placental infections based on current knowledge of placental defenses and how this barrier can be breached. Transmission of pathogens from mother to fetus can occur at two sites of direct contact between maternal cells and specialized fetal cells (trophoblasts) in the human placenta: (i) maternal immune and endothelial cells juxtaposed to extravillous trophoblasts in the uterine implantation site and (ii) maternal blood surrounding the syncytiotrophoblast. Recent findings suggest that the primary vulnerability is in the implantation site. We explore evidence that the placental syncytiotrophoblast evolved as a defense against pathogens, and that inflammation-mediated spontaneous abortion may benefit mother and pathogen. PMID:22169833

  9. Pathways of Youth Development in a Rural Trailer Park

    ERIC Educational Resources Information Center

    MacTavish, Katherine A.; Salamon, Sonya

    2006-01-01

    Limited empirical documentation exists for the developmental pathways available to "rural" youth growing up in low-resource community settings. Drawing on ethnographic data, this article examines the developmental pathways experienced by youth in a rural trailer park. Findings reveal how various factors, some inherent to working poor class status…

  10. Isocitrate Lyase Is Essential for Pathogenicity of the Fungus Leptosphaeria maculans to Canola (Brassica napus)

    PubMed Central

    Idnurm, Alexander; Howlett, Barbara J.

    2002-01-01

    A pathogenicity gene has been identified in Leptosphaeria maculans, the ascomycetous fungus that causes blackleg disease of canola (Brassica napus). This gene encodes isocitrate lyase, a component of the glyoxylate cycle, and is essential for the successful colonization of B. napus. It was identified by a reverse genetics approach whereby a plasmid conferring hygromycin resistance was inserted randomly into the L. maculans genome. Twelve of 516 transformants tested had reduced pathogenicity on cotyledons of B. juncea and B. napus, and 1 of these 12 had a deletion of the isocitrate lyase gene, as well as an insertion of the hygromycin resistance gene. This mutant was unable to grow on fatty acids, including monolaurate, and the isocitrate lyase transcript was not detected. When the wild-type gene was reintroduced into the mutant, growth on monolaurate was restored and pathogenicity was partially restored. L. maculans isocitrate lyase is produced during infection of B. napus cotyledons, while the plant homologue is not. When 2.5% glucose was added to the inoculum of the isocitrate lyase mutant, lesions of sizes similar to those caused by wild-type isolate M1 developed on B. napus cotyledons. These findings suggest that the glyoxylate pathway is essential for disease development by this plant-pathogenic fungus, as has been shown recently for a fungal and bacterial pathogen of animals and a bacterial pathogen of plants. Involvement of the glyoxylate pathway in pathogenesis in animals and plants presents potential drug targets for control of diseases. PMID:12455691

  11. C. elegans detects pathogen-induced translational inhibition to activate immune signaling

    PubMed Central

    Dunbar, Tiffany L.; Yan, Zhi; Balla, Keir M.; Smelkinson, Margery G.; Troemel, Emily R.

    2012-01-01

    Summary Pathogens commonly disrupt host cell processes or cause damage, but the surveillance mechanisms used by animals to monitor these attacks are poorly understood. Upon infection with pathogenic Pseudomonas aeruginosa, the nematode C. elegans upregulates infection response gene irg-1 using the zip-2 bZIP transcription factor. Here we show that P. aeruginosa infection inhibits mRNA translation in the intestine via the endocytosed translation inhibitor Exotoxin A, which leads to an increase in ZIP-2 protein levels. In the absence of infection we find that the zip-2/irg-1 pathway is upregulated following disruption of several core host processes, including inhibition of mRNA translation. ZIP-2 induction is conferred by a conserved upstream open reading frame in zip-2 that could de-repress ZIP-2 translation upon infection. Thus, translational inhibition, a common pathogenic strategy, can trigger activation of an immune surveillance pathway to provide host defense. PMID:22520465

  12. C. elegans detects pathogen-induced translational inhibition to activate immune signaling.

    PubMed

    Dunbar, Tiffany L; Yan, Zhi; Balla, Keir M; Smelkinson, Margery G; Troemel, Emily R

    2012-04-19

    Pathogens commonly disrupt host cell processes or cause damage, but the surveillance mechanisms used by animals to monitor these attacks are poorly understood. Upon infection with pathogenic Pseudomonas aeruginosa, the nematode C. elegans upregulates infection response gene irg-1 using the zip-2 bZIP transcription factor. Here we show that P. aeruginosa infection inhibits mRNA translation in the intestine via the endocytosed translation inhibitor Exotoxin A, which leads to an increase in ZIP-2 protein levels. In the absence of infection we find that the zip-2/irg-1 pathway is upregulated following disruption of several core host processes, including inhibition of mRNA translation. ZIP-2 induction is conferred by a conserved upstream open reading frame in zip-2 that could derepress ZIP-2 translation upon infection. Thus, translational inhibition, a common pathogenic strategy, can trigger activation of an immune surveillance pathway to provide host defense. PMID:22520465

  13. NCI DTP Pathways Services

    Cancer.gov

    Pathways to Development Services Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New Section under development. Please direct inquiries to NCIDTPINFO@mail.nih.gov

  14. Clinical applications of pathogen phylogenies.

    PubMed

    Hartfield, Matthew; Murall, Carmen Lía; Alizon, Samuel

    2014-07-01

    Innovative sequencing techniques now allow the routine access of whole genomes of pathogens, generating vast amounts of data. Phylogenetic trees are a common method for synthesizing this information. Unfortunately, these trees are often seen only as a visual support to guide researchers, thus neglecting the value of employing phylogenetic techniques to perform hypothesis testing on clinical questions. These include investigating how a pathogen spreads within a patient, or whether the infection severity (often measured by virus load) is controlled by viral genetics. Advances in methodology mean the time is ripe for combining phylogenies with clinical data to better understand and fight infectious diseases. PMID:24794010

  15. Cellular defense processes regulated by pathogen-elicited receptor signaling

    NASA Astrophysics Data System (ADS)

    Wu, Rongcong; Goldsipe, Arthur; Schauer, David B.; Lauffenburger, Douglas A.

    2011-06-01

    Vertebrates are constantly threatened by the invasion of microorganisms and have evolved systems of immunity to eliminate infectious pathogens in the body. Initial sensing of microbial agents is mediated by the recognition of pathogens by means of molecular structures expressed uniquely by microbes of a given type. So-called 'Toll-like receptors' are expressed on host epithelial barrier cells play an essential role in the host defense against microbial pathogens by inducing cell responses (e.g., proliferation, death, cytokine secretion) via activation of intracellular signaling networks. As these networks, comprising multiple interconnecting dynamic pathways, represent highly complex multi-variate "information processing" systems, the signaling activities particularly critical for governing the host cell responses are poorly understood and not easily ascertained by a priori theoretical notions. We have developed over the past half-decade a "data-driven" computational modeling approach, on a 'cue-signal-response' combined experiment/computation paradigm, to elucidate key multi-variate signaling relationships governing the cell responses. In an example presented here, we study how a canonical set of six kinase pathways combine to effect microbial agent-induced apoptotic death of a macrophage cell line. One modeling technique, partial least-squares regression, yielded the following key insights: {a} signal combinations most strongly correlated to apoptotic death are orthogonal to those most strongly correlated with release of inflammatory cytokines; {b} the ratio of two key pathway activities is the most powerful predictor of microbe-induced macrophage apoptotic death; {c} the most influential time-window of this signaling activity ratio is surprisingly fast: less than one hour after microbe stimulation.

  16. In vivo assays to evaluate the pathogenic effects of minerals in rodents

    SciTech Connect

    Davis, J.M.G. [Institute of Occupational Medicine Ltd., Edinburgh, Scotland (United Kingdom)

    1993-12-31

    Concern for the pathogenic effects of minerals centers on two pathological conditions: fibrosis and neoplasia. For many years it has been known that some dusts (e.g. quartz and coal mine dusts) can produce nodular pulmonary fibrosis when inhaled by humans and that some fibrous dusts could also cause cancer in addition to asbestosis. In order to assess the pathogenicity of various dusts and to learn more about the mechanisms of this pathogenicity, a number of in vivo assays have been developed. This article focuses on the principles underlying in vivo methods and reviews some of the data and significant discoveries. 135 refs.

  17. Lab-on-a-Chip Pathogen Sensors for Food Safety

    PubMed Central

    Yoon, Jeong-Yeol; Kim, Bumsang

    2012-01-01

    There have been a number of cases of foodborne illness among humans that are caused by pathogens such as Escherichia coli O157:H7, Salmonella typhimurium, etc. The current practices to detect such pathogenic agents are cell culturing, immunoassays, or polymerase chain reactions (PCRs). These methods are essentially laboratory-based methods that are not at all real-time and thus unavailable for early-monitoring of such pathogens. They are also very difficult to implement in the field. Lab-on-a-chip biosensors, however, have a strong potential to be used in the field since they can be miniaturized and automated; they are also potentially fast and very sensitive. These lab-on-a-chip biosensors can detect pathogens in farms, packaging/processing facilities, delivery/distribution systems, and at the consumer level. There are still several issues to be resolved before applying these lab-on-a-chip sensors to field applications, including the pre-treatment of a sample, proper storage of reagents, full integration into a battery-powered system, and demonstration of very high sensitivity, which are addressed in this review article. Several different types of lab-on-a-chip biosensors, including immunoassay- and PCR-based, have been developed and tested for detecting foodborne pathogens. Their assay performance, including detection limit and assay time, are also summarized. Finally, the use of optical fibers or optical waveguide is discussed as a means to improve the portability and sensitivity of lab-on-a-chip pathogen sensors. PMID:23112625

  18. Nuclear jasmonate and salicylate signaling and crosstalk in defense against pathogens

    PubMed Central

    Gimenez-Ibanez, Selena; Solano, Roberto

    2013-01-01

    An extraordinary progress has been made over the last two decades on understanding the components and mechanisms governing plant innate immunity. After detection of a pathogen, effective plant resistance depends on the activation of a complex signaling network integrated by small signaling molecules and hormonal pathways, and the balance of these hormone systems determines resistance to particular pathogens. The discovery of new components of hormonal signaling pathways, including plant nuclear hormone receptors, is providing a picture of complex crosstalk and induced hormonal changes that modulate disease and resistance through several protein families that perceive hormones within the nucleus and lead to massive gene induction responses often achieved by de-repression. This review highlights recent advances in our understanding of positive and negative regulators of these hormones signaling pathways that are crucial regulatory targets of hormonal crosstalk in disease and defense. We focus on the most recent discoveries on the jasmonate and salicylate pathway components that explain their crosstalk with other hormonal pathways in the nucleus. We discuss how these components fine-tune defense responses to build a robust plant immune system against a great number of different microbes and, finally, we summarize recent discoveries on specific nuclear hormonal manipulation by microbes which exemplify the ingenious ways by which pathogens can take control over the plant’s hormone signaling network to promote disease. PMID:23577014

  19. Wound care clinical pathway: a conceptual model.

    PubMed

    Barr, J E; Cuzzell, J

    1996-08-01

    A clinical pathway is a written sequence of clinical processes or events that guides a patient with a defined problem toward an expected outcome. Clinical pathways are tools to assist with the cost-effective management of clinical outcomes related to specific problems or disease processes. The primary obstacles to developing clinical pathways for wound care are the chronic natures of some wounds and the many variables that can delay healing. The pathway introduced in this article was modeled upon the three phases of tissue repair: inflammatory, proliferative, and maturation. This physiology-based model allows clinicians to identify and monitor outcomes based on observable and measurable clinical parameters. The pathway design, which also includes educational and behavioral outcomes, allows the clinician to individualize the expected timeframe for outcome achievement based on individual patient criteria and expert judgement. Integral to the pathway are the "4P's" which help standardize the clinical processes by wound type: Protocols, Policies, Procedures, and Patient education tools. Four categories into which variances are categorized based on the cause of the deviation from the norm are patient, process/system, practitioner, and planning/discharge. Additional research is warranted to support the value of this clinical pathway in the clinical arena. PMID:8826117

  20. MANAGING URBAN WATERSHED PATHOGEN CONTAMINATION

    EPA Science Inventory

    This presentation is a summary of the EPA National Risk Management Research Laboratory (NRMRL) publication entitled Managing Urban Watershed Pathogen Contamination, EPA/600/R-03/111 (September 2003). It is available on the internet at http://www.epa.gov/ednnrmrl/repository/water...

  1. Bloodborne Pathogens Exposure Control Plan.

    ERIC Educational Resources Information Center

    National Child Care Association, Atlanta, GA.

    This sample exposure control plan is a guide to assist child care providers in complying with the blood-borne pathogens standard issued by the Occupational Safety and Health Administration (OSHA). The standard requires employers to establish a written exposure control plan by May 5, 1992 (for exposure to microorganisms in human blood that cause…

  2. Microbial Forensics and Plant Pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New awareness of the vulnerability of a nation's agricultural infrastructure to the intentional introduction of pathogens or pests has led to the enhancement of programs for prevention and preparedness. A necessary component of a balanced bio-security plan is the capability to determine whether an ...

  3. The Evolution of Foodborne Pathogens

    Microsoft Academic Search

    Galeb S. Abu-Ali; Shannon D. Manning

    \\u000a Despite continuous advances in food safety and disease surveillance, control, and prevention, foodborne bacterial infections\\u000a remain a major public health concern. Because foodborne pathogens are commonly exposed to multiple environmental stressors,\\u000a such as low pH and antibiotics, most have evolved specific mechanisms to facilitate survival in adverse environments.

  4. COMPARATIVE GENOMICS OF PATHOGENIC LEPTOSPIRA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pathogenic Leptospira possess two circular chromosomal replicons, CI and CII. The genetic content of CI, the larger replicon, resembles a typical bacterial chromosome and possesses all rRNA, tRNA, and most housekeeping genes. The functional role of the smaller chromosome, CII, is less clear, beca...

  5. LABORATORY MAINTENANCE OF PATHOGENIC LEPTOSPIRA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Analysis of Leptospira requires use of specialized media for growth, maintenance, and storage of viable bacteria that can be used in experimental protocols in a predictable manner. However, pathogenic Leptospira are fastidious bacteria with unusual nutritional requirements. These problems make pri...

  6. Pathogenicity of aseptic Bursaphelenchus xylophilus.

    PubMed

    Zhu, Li-hua; Ye, Jianren; Negi, Sapna; Xu, Xu-ling; Wang, Zhang-li; Ji, Jin-yi

    2012-01-01

    Pine wilt is a disease of pine (Pinus spp.) caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus. However, the pathogenic mechanism of pine wilt disease (PWD) remains unclear. Although the PWN was thought to be the only pathogenic agent associated with this disease, a potential role for bacterial symbionts in the disease process was recently proposed. Studies have indicated that aseptic PWNs do not cause PWD in aseptic pine trees, while PWNs associated with bacteria cause wilting symptoms. To investigate the pathogenicity of the PWN and its associated bacteria, 3-month-old microcuttings derived from certain clones of Pinus densiflora Siebold & Zucc. produced in vitro were inoculated under aseptic conditions with aseptic PWNs, non-aseptic PWNs and bacteria isolated from the nematodes. Six-month-old aseptic P. densiflora microcuttings and 7-month-old P. massoniana seedlings were also inoculated under aseptic conditions with aseptic PWNs and non-aseptic PWNs. The results showed that the aseptic microcuttings and seedlings inoculated with aseptic PWNs or non-aseptic PWNs wilted, while those inoculated with bacterial isolates did not wilt. Nematodes were recovered from wilted microcuttings and seedlings inoculated with aseptic PWNs and non-aseptic PWNs, and the asepsis of nematodes recovered from aseptic PWN-inoculated microcuttings and seedlings was reconfirmed by culturing them in NB liquid medium at 30°C for more than 7 days. Taken together, the results indicate that the asepsis of PWN did not cause the loss of pathogenicity. PMID:22662271

  7. Asian citrus psyllid viral pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly discovered viral pathogen of Asian citrus psyllid, AsCP, Diaphorina citri, Kuwayama (Psyllidae: Hemiptera) was classified as a Reoviridae. This virus may serve as a biological control agent for AsCP. The AsCP is an efficient vector of the plant-infecting bacterium (Candidatus Liberibacter as...

  8. PATHOGENIC 'NAEGLERIA': DISTRIBUTION IN NATURE

    EPA Science Inventory

    Infection in man with pathogenic Naegleria, a free-living soil amoeba, results in a usually fatal disease entity known as primary amoebic meningoencephalitis. Epidemiological data usually included exposure to freshwater lakes or streams within the week prior to onset. However, no...

  9. GENOME ANALYSIS OF PATHOGENIC LEPTOSPIRA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome sequences of four strains of pathogenic Leptospira have been completed. These data have dramatically improved our knowledge of the coding potential of these bacteria. The organization of genetic material in Leptospira appears to be quite fluid, with many rearrangements being detected throug...

  10. EXTRAINTESTINAL PATHOGENIC ESCHERICHIA COLI (EXPEC)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Extraintestinal pathogenic Escherichia coli (ExPEC) possess virulence traits that allow them to invade, colonize, and induce disease in bodily sites outside of the gastrointestinal tract. Human diseases caused by ExPEC include urinary tract infections, neonatal meningitis, sepsis, pneumonia, surgic...

  11. Pathogenicity of Mycobacterium tuberculosis Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage

    PubMed Central

    Saquib, Najmuddin; Sinha, Neeraj; Siddiqui, Zaved; Manivel, Venkatasamy; Chatterjee, Samrat; Rao, Kanury V. S.

    2014-01-01

    The success of Mycobacterium tuberculosis as a pathogen derives from its facile adaptation to the intracellular milieu of human macrophages. To explore this process, we asked whether adaptation also required interference with the metabolic machinery of the host cell. Temporal profiling of the metabolic flux, in cells infected with differently virulent mycobacterial strains, confirmed that this was indeed the case. Subsequent analysis identified the core subset of host reactions that were targeted. It also elucidated that the goal of regulation was to integrate pathways facilitating macrophage survival, with those promoting mycobacterial sustenance. Intriguingly, this synthesis then provided an axis where both host- and pathogen-derived factors converged to define determinants of pathogenicity. Consequently, whereas the requirement for macrophage survival sensitized TB susceptibility to the glycemic status of the individual, mediation by pathogen ensured that the virulence properties of the infecting strain also contributed towards the resulting pathology. PMID:25058590

  12. Lactobacillus protects the integrity of intestinal epithelial barrier damaged by pathogenic bacteria

    PubMed Central

    Yu, Qinghua; Yuan, Lixia; Deng, Jun; Yang, Qian

    2015-01-01

    Pathogens invade intestinal mucosal barrier through phagocytosis of antigen presenting cells (dendritic cell, microfold cells), or through the invasion into the intestinal epithelial directly. Some pathogens could damage the cell junction between epithelial cells and use the paracellular pathway as an entrance to invade. Moreover, some Lactobacillus could inhibit the adhesion of the pathogens and protect the integrity of the cell junction and mucosal barrier. This research focused on the potential therapeutic effect of Lactobacillus fructosus (L. fructosus) C2 to attenuate ETEC K88 or S. typhimurium SL1344 induced changes to mucosal barrier. The results demonstrated that treatment of polarized Caco-2 cells with L. fructosus C2 reduced the permeation of dextran, and expression of IL-8, p-ERK, and p-JNK when cells were infected with pathogenic bacteria. The findings indicated that L. fructosus C2 exerted a protective effect against the damage to the integrity of Caco-2 cells by ETEC or S. typhimurium infection.

  13. Organomercury Pathway Map

    NSDL National Science Digital Library

    Nasevicius, Aidas.

    The University of Minnesota Biocatalysis/Biodegradation Database (UM/BBD) contains "microbial biocatalytic reactions and biodegradation pathways primarily for xenobiotic, chemical compounds." A new microbial enzyme-catalyzed reactions has been posted for Organomercury. The Organomercury pathway map highlights mercury, a highly toxic heavy metal used "as a pesticide, herbicide, fungicide, disinfectant and a preservative in cosmetics." The organomercury pathway map includes organisms which can initiate the pathway. The pathway map provides detailed information on each hyperlinked step, including graphics, product/substrate reactions, and external links to further information.

  14. Large-Scale Elucidation of Drug Response Pathways in Humans

    PubMed Central

    Silberberg, Yael; Gottlieb, Assaf; Kupiec, Martin; Ruppin, Eytan

    2012-01-01

    Abstract Elucidating signaling pathways is a fundamental step in understanding cellular processes and developing new therapeutic strategies. Here we introduce a method for the large-scale elucidation of signaling pathways involved in cellular response to drugs. Combining drug targets, drug response expression profiles, and the human physical interaction network, we infer 99 human drug response pathways and study their properties. Based on the newly inferred pathways, we develop a pathway-based drug-drug similarity measure and compare it to two common, gold standard drug-drug similarity measures. Remarkably, our measure provides better correspondence to these gold standards than similarity measures that are based on associations between drugs and known pathways, or on drug-specific gene expression profiles. It further improves the prediction of drug side effects and indications, elucidating specific response pathways that may be associated with these drug properties. Supplementary Material for this article is available at www.liebertonline.com/cmb. PMID:22300318

  15. Aromatic pathways in carbathiaporphyrins.

    PubMed

    Valiev, Rashid R; Fliegl, Heike; Sundholm, Dage

    2015-02-19

    Magnetically induced current densities and current pathways have been calculated for carbaporphyrins and carbathiaporphyrins using the gauge including magnetically induced current (GIMIC) method. The aromatic character and current pathways are obtained from the calculated current density susceptibilities. The current-density calculations show that five of the studied carbaporphyrinoids are aromatic, two are antiaromatic, and one is nonaromatic. The analysis of the current pathways of the investigated molecules reveals some general trends for the current flow in carbaporphyrinoids. Insertion of a CH2 group into the all-carbon ring generally cuts or restricts the current flow, leading to a stronger current of the alternative pathway of the ring. No obvious trends regarding the current strengths and pathways of the thiophene and cyclopentadienyl rings were obtained. The present study shows that it is indeed difficult to predict the electron delocalization pathways of general carbaporphyrinoids. Thus, a careful analysis of the current density is necessary for determining their electron delocalization pathways. PMID:25658493

  16. Identifying pathogenic processes by integrating microarray data with prior knowledge

    PubMed Central

    2014-01-01

    Background It is of great importance to identify molecular processes and pathways that are involved in disease etiology. Although there has been an extensive use of various high-throughput methods for this task, pathogenic pathways are still not completely understood. Often the set of genes or proteins identified as altered in genome-wide screens show a poor overlap with canonical disease pathways. These findings are difficult to interpret, yet crucial in order to improve the understanding of the molecular processes underlying the disease progression. We present a novel method for identifying groups of connected molecules from a set of differentially expressed genes. These groups represent functional modules sharing common cellular function and involve signaling and regulatory events. Specifically, our method makes use of Bayesian statistics to identify groups of co-regulated genes based on the microarray data, where external information about molecular interactions and connections are used as priors in the group assignments. Markov chain Monte Carlo sampling is used to search for the most reliable grouping. Results Simulation results showed that the method improved the ability of identifying correct groups compared to traditional clustering, especially for small sample sizes. Applied to a microarray heart failure dataset the method found one large cluster with several genes important for the structure of the extracellular matrix and a smaller group with many genes involved in carbohydrate metabolism. The method was also applied to a microarray dataset on melanoma cancer patients with or without metastasis, where the main cluster was dominated by genes related to keratinocyte differentiation. Conclusion Our method found clusters overlapping with known pathogenic processes, but also pointed to new connections extending beyond the classical pathways. PMID:24758699

  17. Top 10 plant pathogenic bacteria in molecular plant pathology.

    PubMed

    Mansfield, John; Genin, Stephane; Magori, Shimpei; Citovsky, Vitaly; Sriariyanum, Malinee; Ronald, Pamela; Dow, Max; Verdier, Valérie; Beer, Steven V; Machado, Marcos A; Toth, Ian; Salmond, George; Foster, Gary D

    2012-08-01

    Many plant bacteriologists, if not all, feel that their particular microbe should appear in any list of the most important bacterial plant pathogens. However, to our knowledge, no such list exists. The aim of this review was to survey all bacterial pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate the bacterial pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 458 votes from the international community, and allowed the construction of a Top 10 bacterial plant pathogen list. The list includes, in rank order: (1) Pseudomonas syringae pathovars; (2) Ralstonia solanacearum; (3) Agrobacterium tumefaciens; (4) Xanthomonas oryzae pv. oryzae; (5) Xanthomonas campestris pathovars; (6) Xanthomonas axonopodis pathovars; (7) Erwinia amylovora; (8) Xylella fastidiosa; (9) Dickeya (dadantii and solani); (10) Pectobacterium carotovorum (and Pectobacterium atrosepticum). Bacteria garnering honourable mentions for just missing out on the Top 10 include Clavibacter michiganensis (michiganensis and sepedonicus), Pseudomonas savastanoi and Candidatus Liberibacter asiaticus. This review article presents a short section on each bacterium in the Top 10 list and its importance, with the intention of initiating discussion and debate amongst the plant bacteriology community, as well as laying down a benchmark. It will be interesting to see, in future years, how perceptions change and which bacterial pathogens enter and leave the Top 10. PMID:22672649

  18. EHFPI: a database and analysis resource of essential host factors for pathogenic infection

    PubMed Central

    Liu, Yang; Xie, Dafei; Han, Lu; Bai, Hui; Li, Fei; Wang, Shengqi; Bo, Xiaochen

    2015-01-01

    High-throughput screening and computational technology has greatly changed the face of microbiology in better understanding pathogen–host interactions. Genome-wide RNA interference (RNAi) screens have given rise to a new class of host genes designated as Essential Host Factors (EHFs), whose knockdown effects significantly influence pathogenic infections. Therefore, we present the first release of a manually-curated bioinformatics database and analysis resource EHFPI (Essential Host Factors for Pathogenic Infection, http://biotech.bmi.ac.cn/ehfpi). EHFPI captures detailed article, screen, pathogen and phenotype annotation information for a total of 4634 EHF genes of 25 clinically important pathogenic species. Notably, EHFPI also provides six powerful and data-integrative analysis tools, i.e. EHF Overlap Analysis, EHF-pathogen Network Analysis, Gene Enrichment Analysis, Pathogen Interacting Proteins (PIPs) Analysis, Drug Target Analysis and GWAS Candidate Gene Analysis, which advance the comprehensive understanding of the biological roles of EHF genes, as in diverse perspectives of protein–protein interaction network, drug targets and diseases/traits. The EHFPI web interface provides appropriate tools that allow efficient query of EHF data and visualization of custom-made analysis results. EHFPI data and tools shall keep available without charge and serve the microbiology, biomedicine and pharmaceutics research communities, to finally facilitate the development of diagnostics, prophylactics and therapeutics for human pathogens. PMID:25414353

  19. Molecular neurodegeneration: basic biology and disease pathways.

    PubMed

    Vassar, Robert; Zheng, Hui

    2014-01-01

    The field of neurodegeneration research has been advancing rapidly over the past few years, and has provided intriguing new insights into the normal physiological functions and pathogenic roles of a wide range of molecules associated with several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, and Down syndrome. Recent developments have also facilitated initial efforts to translate preclinical discoveries toward novel therapeutic approaches and clinical trials in humans. These recent developments are reviewed in the current Review Series on "Molecular Neurodegeneration: Basic Biology and Disease Pathways" in a number of state-of-the-art manuscripts that cover themes presented at the Third International Conference on Molecular Neurodegeneration: "Basic biology and disease pathways" held in Cannes, France, September, 2013. PMID:25248568

  20. 40 CFR 503.32 - Pathogens.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STANDARDS FOR THE USE OR DISPOSAL OF SEWAGE SLUDGE Pathogens and Vector Attraction Reduction § 503.32 Pathogens. (a) Sewage sludge—Class A. (1) The...

  1. INOCULATION AND GROWTH WITH FOLIAR PATHOGENIC FUNGI

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter describes methods for evaluating responses of Medicago truncatula to foliar plant-pathogenic fungi. Growth of plants, preparation of inoculum, incubation conditions, and disease assessment are described for five necrotrophic pathogens (Ascochyta lentis, Ascochyta rabiei, Colletotrichum ...

  2. 29 CFR 1915.1030 - Bloodborne pathogens.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 7 2010-07-01 2010-07-01 false Bloodborne pathogens. 1915.1030 Section 1915.1030 Labor Regulations...Toxic and Hazardous Substances § 1915.1030 Bloodborne pathogens. Note: The requirements applicable to shipyard...

  3. 29 CFR 1915.1030 - Bloodborne pathogens.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 7 2012-07-01 2012-07-01 false Bloodborne pathogens. 1915.1030 Section 1915.1030 Labor Regulations...Toxic and Hazardous Substances § 1915.1030 Bloodborne pathogens. Note: The requirements applicable to shipyard...

  4. 29 CFR 1915.1030 - Bloodborne pathogens.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 7 2011-07-01 2011-07-01 false Bloodborne pathogens. 1915.1030 Section 1915.1030 Labor Regulations...Toxic and Hazardous Substances § 1915.1030 Bloodborne pathogens. Note: The requirements applicable to shipyard...

  5. 29 CFR 1915.1030 - Bloodborne pathogens.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 7 2014-07-01 2014-07-01 false Bloodborne pathogens. 1915.1030 Section 1915.1030 Labor Regulations...Toxic and Hazardous Substances § 1915.1030 Bloodborne pathogens. Note: The requirements applicable to shipyard...

  6. 29 CFR 1915.1030 - Bloodborne pathogens.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 7 2013-07-01 2013-07-01 false Bloodborne pathogens. 1915.1030 Section 1915.1030 Labor Regulations...Toxic and Hazardous Substances § 1915.1030 Bloodborne pathogens. Note: The requirements applicable to shipyard...

  7. ERD Research on Nutrient and Pathogen Dynamics

    EPA Science Inventory

    Slide presentation giving an overview on the ERD research on nutrient and pathogen dynamics. Focus is on characterizing the dynamics of pathogen and nutrient stressors in the environment to support water quality objectives....

  8. Overviews of Pathogen Emergence: Which Pathogens Emerge, When and Why?

    Microsoft Academic Search

    S. Cleaveland; D. T. Haydon; L. Taylor

    An emerging pathogen has been defined as the causative agent of an infectious disease whose incidence is increasing following\\u000a its appearance in a new host population or whose incidence is increasing in an existing population as a result of long-term\\u000a changes in its underlying epidemiology (Woolhouse and Dye 2001). Although we appear to be in a period where novel diseases

  9. Comparative Phylogenomics of Pathogenic and Non-Pathogenic Mycobacterium

    PubMed Central

    Prasanna, Arun N.; Mehra, Sarika

    2013-01-01

    Mycobacterium species are the source of a variety of infectious diseases in a range of hosts. Genome based methods are used to understand the adaptation of each pathogenic species to its unique niche. In this work, we report the comparison of pathogenic and non-pathogenic Mycobacterium genomes. Phylogenetic trees were constructed using sequence of core orthologs, gene content and gene order. It is found that the genome based methods can better resolve the inter-species evolutionary distances compared to the conventional 16S based tree. Phylogeny based on gene order highlights distinct evolutionary characteristics as compared to the methods based on sequence, as illustrated by the shift in the relative position of M. abscessus. This difference in gene order among the Mycobacterium species is further investigated using a detailed synteny analysis. It is found that while rearrangements between some Mycobacterium genomes are local within synteny blocks, few possess global rearrangements across the genomes. The study illustrates how a combination of different genome based methods is essential to build a robust phylogenetic relationship between closely related organisms. PMID:24015186

  10. Plant innate immunity against human bacterial pathogens

    PubMed Central

    Melotto, Maeli; Panchal, Shweta; Roy, Debanjana

    2014-01-01

    Certain human bacterial pathogens such as the enterohemorrhagic Escherichia coli and Salmonella enterica are not proven to be plant pathogens yet. Nonetheless, under certain conditions they can survive on, penetrate into, and colonize internal plant tissues causing serious food borne disease outbreaks. In this review, we highlight current understanding on the molecular mechanisms of plant responses against human bacterial pathogens and discuss salient common and contrasting themes of plant interactions with phytopathogens or human pathogens. PMID:25157245

  11. Exploitation of host epithelial signaling networks by respiratory bacterial pathogens.

    PubMed

    Li, Jian-Dong

    2003-01-01

    Although tremendous effort has been put towards identifying the surface molecules of nontypeable Haemophilus influenzae (NTHi) for vaccine development over the past decades, it is only recently that we have begun to appreciate the intricate host epithelial signaling networks activated by NTHi, an important human pathogen causing respiratory infections. From what has been reported, it is evident that NTHi activates multiple signaling pathways in host epithelial cells that, in turn, inadvertently contribute to the pathogenesis. Among those signaling pathways, activation of NF-kappaB leads to up-regulation of IL-1beta, IL-8 and TNF-alpha, mucin MUC2 and Toll-like receptor 2 (TLR2), whereas activation of p38 MAP kinase mediates not only up-regulation of inflammatory mediators and mucin MUC5AC but also down-regulation of TLR2. Interestingly, NTHi-induced activation of the PI3K-Akt pathway, however, leads to inhibition of p38 mitogen-activated protein (MAP) kinase. Moreover, the TGF-beta-Smad signaling pathway cooperates with NF-kappaB to mediate up-regulation of mucin MUC2. Finally, glucocorticoids synergistically enhance NTHi-induced TLR2 expression via specific up-regulation of the MAP kinase phosphatase-1 that, in turn, leads to inactivation of p38 MAP kinase, the negative regulator for TLR2 expression. These studies may bring new insights into the molecular pathogenesis of NTHi-induced infections and open up novel therapeutic targets for these diseases. PMID:12686724

  12. Jasmonate-Inducible Genes Are Activated in Rice by Pathogen Attack without a Concomitant Increase in Endogenous Jasmonic Acid Levels.

    PubMed Central

    Schweizer, P.; Buchala, A.; Silverman, P.; Seskar, M.; Raskin, I.; Metraux, J. P.

    1997-01-01

    The possible role of the octadecanoid signaling pathway with jasmonic acid (JA) as the central component in defense-gene regulation of pathogen-attacked rice was studied. Rice (Oryza sativa L.) seedlings were treated with JA or inoculated with the rice blast fungus Magnaporthe grisea (Hebert) Barr., and gene-expression patterns were compared between the two treatments. JA application induced the accumulation of a number of pathogenesis-related (PR) gene products at the mRNA and protein levels, but pathogen attack did not enhance the levels of (-)-JA during the time required for PR gene expression. Pathogen-induced accumulation of PR1-like proteins was reduced in plants treated with tetcyclacis, a novel inhibitor of jasmonate biosynthesis. There was an additive and negative interaction between JA and an elicitor from M. grisea with respect to induction of PR1-like proteins and of an abundant JA-and wound-induced protein of 26 kD, respectively. Finally, activation of the octadecanoid signaling pathway and induction of a number of PR genes by exogenous application of JA did not confer local acquired resistance to rice. The data suggest that accumulation of nonconjugated (-)-JA is not necessary for induction of PR genes and that JA does not orchestrate localized defense responses in pathogen-attacked rice. Instead, JA appears to be embedded in a signaling network with another pathogen-induced pathway(s) and may be required at a certain minimal level for induction of some PR genes. PMID:12223690

  13. Page 1 of 16 Bloodborne Pathogens Program

    E-print Network

    Page 1 of 16 Bloodborne Pathogens Program Revised July, 5 2012 #12;Page 2 of 16 Table of Contents 1 will be potentially exposed to Bloodborne Pathogens. By following these procedures, the safety of the working 4 of 16 2.0 EXPOSURE CONTROL METHODS Bloodborne pathogens (BBP) are present in human blood and can

  14. Foodborne pathogen detection using hyperspectral imaging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foodborne pathogens can cause various diseases and even death when humans consume foods contaminated with microbial pathogens. Traditional culture-based direct plating methods are still the “gold standard” for presumptive-positive pathogen screening. Although considerable research has been devoted t...

  15. BIODIVERSITY Insect pests and pathogens of Australian

    E-print Network

    in their native environments. Keywords Biological invasions, fungal tree pathogens, new encounter diseases, novel threatened by invasive alien pests and pathogens (Wingfield et al., 2010). The reality of this threat first invasive alien pest and pathogen problems have continued to appear in native woody ecosys- tems and forests

  16. Genomic islands in pathogenic and environmental microorganisms

    Microsoft Academic Search

    Ulrich Dobrindt; Bianca Hochhut; Ute Hentschel; Jörg Hacker

    2004-01-01

    Horizontal gene transfer is an important mechanism for the evolution of microbial genomes. Pathogenicity islands — mobile genetic elements that contribute to rapid changes in virulence potential — are known to have contributed to genome evolution by horizontal gene transfer in many bacterial pathogens. Increasing evidence indicates that equivalent elements in non-pathogenic species — genomic islands — are important in

  17. Phylogeography of the fungal pathogen Histoplasma capsulatum

    Microsoft Academic Search

    Takao Kasuga; Thomas J. White; Gina Koenig; Juan Mcewen; Angela Restrepo; Elizabetha Castaneda; Carlos Da Silva Lacaz; Elisabeth M. Heins-Vaccari; Roseli S. De Freitas; Rosely M. Zancope-Oliveira; Zhenyu Qin; Ricardo Negroni; Deidre A. Carter; Yuzuru Mikami; Miki Tamura; Maria Lucia Taylor; Georgina F. Miller; Natteewan Poonwan; John W. Taylor

    2003-01-01

    Until recently, Histoplasma capsulatum was believed to harbour three varieties, var. capsulatum (chiefly a New World human pathogen), var. duboisii (an African human pathogen) and var. farciminosum (an Old World horse pathogen), which varied in clinical manifestations and geographical distribution. We analysed the phylogenetic relationships of 137 individuals representing the three varieties from six continents using DNA sequence variation in

  18. Variation between Pathogenic Serovars within Salmonella Pathogenicity Islands

    PubMed Central

    Amavisit, P.; Lightfoot, D.; Browning, G. F.; Markham, P. F.

    2003-01-01

    Although four of the five Salmonella pathogenicity islands (SPIs) have been characterized in detail for Salmonella enterica serovar Typhimurium, and the fifth has been characterized for Salmonella enterica serovar Dublin, there have been limited studies to examine them in detail in a range of pathogenic serovars of S. enterica. The aim of this study was to examine these regions, shown to be crucial in virulence, in pathogenic serovars to identify any major deletions or insertions that may explain variation in virulence and provide further understanding of the elements involved in the evolution of these regions. Multiple strains of each of the 13 serovars were compared by Southern blot hybridization using a series of probes that together encompassed the full length of all five SPIs. With the exception of serovar Typhimurium, all strains of the same serovar were identical in all five SPIs. Those serovars that differed from serovar Typhimurium in SPI-1 to SPI-4 and from serovar Dublin in SPI-5 were examined in more detail in the variant regions by PCR, and restriction endonuclease digestion and/or DNA sequencing. While most variation in hybridization patterns was attributable to loss or gain of single restriction endonuclease cleavage sites, three regions, in SPI-1, SPI-3, and SPI-5, had differences due to major insertions or deletions. In SPI-1 the avrA gene was replaced by a 200-base fragment in three serovars, as reported previously. In SPI-5, two serovars had acquired an insertion with similarity to the pagJ and pagK genes between pipC and pipD. In SPI-3 the genes sugR and rhuM were deleted in most serovars and in some were replaced by sequences that were very similar to either the Escherichia coli fimbrial operon, flanked by two distinct insertion sequence elements, or to the E. coli retron phage ?R73. The distribution of these differences suggests that there have been a number of relatively recent horizontal transfers of genes into S. enterica and that in some cases the same event has occurred in multiple lineages of S. enterica. Thus, it seems that insertion sequences and retron phages are likely to be involved in continuing evolution of the pathogenicity islands of pathogenic Salmonella serovars. PMID:12775700

  19. UV signaling pathways within the skin

    PubMed Central

    Chen, Hongxiang; Weng, Qing Yu; Fisher, David E.

    2014-01-01

    The effects of UVR on the skin include tanning, carcinogenesis, immunomodulation, and synthesis of vitamin D, among others. Melanocortin 1 receptor polymorphisms correlate with skin pigmentation, UV sensitivity, and skin cancer risk. This article reviews pathways through which UVR induces cutaneous stress and the pigmentation response. Modulators of the UV tanning pathway include sunscreen agents, MC1R activators, adenylate cyclase activators, phosphodiesterase 4D3 inhibitors, T oligos, and MITF regulators such as histone deacetylase (HDAC)-inhibitors. UVR, as one of the most ubiquitous carcinogens, represents both a challenge and enormous opportunity in skin cancer prevention. PMID:24759085

  20. [Molecular components of JAK/STAT signaling pathway and its connection with transcription machinery].

    PubMed

    Shaposhnikov, A V; Komar'kov, I F; Lebedeva, L A; Shidlovski?, Iu V

    2013-01-01

    JAK/STAT is one of the conservative signaling pathways in higher eukaryotes which plays a critical role in different ontogenesis processes. This article gives a review of the pathway structure at the molecular level, mainly in a model organism Drosophila. There are data about relationship of the signaling pathway and transcription machinery of higher eukaryotes. PMID:23888769

  1. The Drosophila Toll pathway controls but does not clear Candida glabrata infections.

    PubMed

    Quintin, Jessica; Asmar, Joelle; Matskevich, Alexey A; Lafarge, Marie-Céline; Ferrandon, Dominique

    2013-03-15

    The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host. PMID:23401590

  2. PATHWAYS - ELECTRON TUNNELING PATHWAYS IN PROTEINS

    NASA Technical Reports Server (NTRS)

    Beratan, D. N.

    1994-01-01

    The key to understanding the mechanisms of many important biological processes such as photosynthesis and respiration is a better understanding of the electron transfer processes which take place between metal atoms (and other groups) fixed within large protein molecules. Research is currently focused on the rate of electron transfer and the factors that influence it, such as protein composition and the distance between metal atoms. Current models explain the swift transfer of electrons over considerable distances by postulating bridge-mediated tunneling, or physical tunneling pathways, made up of interacting bonds in the medium around and between donor and acceptor sites. The program PATHWAYS is designed to predict the route along which electrons travel in the transfer processes. The basic strategy of PATHWAYS is to begin by recording each possible path element on a connectivity list, including in each entry which two atoms are connected and what contribution the connection would make to the overall rate if it were included in a pathway. The list begins with the bonded molecular structure (including the backbone sequence and side chain connectivity), and then adds probable hydrogen bond links and through-space contacts. Once this list is completed, the program runs a tree search from the donor to the acceptor site to find the dominant pathways. The speed and efficiency of the computer search offers an improvement over manual techniques. PATHWAYS is written in FORTRAN 77 for execution on DEC VAX series computers running VMS. The program inputs data from four data sets and one structure file. The software was written to input BIOGRAF (old format) structure files based on x-ray crystal structures and outputs ASCII files listing the best pathways and BIOGRAF vector files containing the paths. Relatively minor changes could be made in the input format statements for compatibility with other graphics software. The executable and source code are included with the distribution. The main memory requirement for execution is 2.6 Mb. This program is available in DEC VAX BACKUP format on a 9-track 1600 BPI magnetic tape (standard distribution) or on a TK50 tape cartridge. PATHWAYS was developed in 1988. PATHWAYS is a copyrighted work with all copyright vested in NASA. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. BIOGRAF is a trademark of Molecular Simulations, Inc., Sunnyvale, CA.

  3. Pathways of fear and anxiety in dentistry: A review.

    PubMed

    Carter, Ava Elizabeth; Carter, Geoff; Boschen, Mark; AlShwaimi, Emad; George, Roy

    2014-11-16

    The aim of this article was to analyze the theories underpinning dental fear, anxiety and phobias. To be included, articles must have been published between the years of 1949 and 2013 concerning fears and phobias within dentistry and/or psychiatry. Of 200 articles originally under review, 140 were included and reviewed by the authors.Five specific pathways relating to dental fear and anxiety were identified; Cognitive Conditioning, Informative, Visual Vicarious, Verbal Threat, and Parental. Eight currently accepted management techniques across all dental disciplines for dental fear and anxiety were identified. Further research is required to identify clinical diagnosis and treatment for fears originating from different pathways. PMID:25405187

  4. Pathways of fear and anxiety in dentistry: A review

    PubMed Central

    Carter, Ava Elizabeth; Carter, Geoff; Boschen, Mark; AlShwaimi, Emad; George, Roy

    2014-01-01

    The aim of this article was to analyze the theories underpinning dental fear, anxiety and phobias. To be included, articles must have been published between the years of 1949 and 2013 concerning fears and phobias within dentistry and/or psychiatry. Of 200 articles originally under review, 140 were included and reviewed by the authors.Five specific pathways relating to dental fear and anxiety were identified; Cognitive Conditioning, Informative, Visual Vicarious, Verbal Threat, and Parental. Eight currently accepted management techniques across all dental disciplines for dental fear and anxiety were identified. Further research is required to identify clinical diagnosis and treatment for fears originating from different pathways. PMID:25405187

  5. Review article Cardioprotective signaling to mitochondria

    E-print Network

    Brand, Paul H.

    Review article Cardioprotective signaling to mitochondria Keith D. Garlid a, , Alexandre D.T. Costa species Permeability transition Signaling pathways Mitochondria are central players in the pathophysiology the plasma membrane and migrate to mitochondria. The signalosome­mitochondria interaction then initiates

  6. Antimicrobial resistance of mastitis pathogens.

    PubMed

    Oliver, Stephen P; Murinda, Shelton E

    2012-07-01

    Antibiotics are used extensively in the dairy industry to combat disease and to improve animal performance. Antibiotics such as penicillin, cephalosporin, streptomycin, and tetracycline are used for the treatment and prevention of diseases affecting dairy cows caused by a variety of gram-positive and gram-negative bacteria. Antibiotics are often administrated routinely to entire herds to prevent mastitis during the dry period. An increase in the incidence of disease in a herd generally results in increased use of antimicrobials, which in turn increases the potential for antibiotic residues in milk and the potential for increased bacterial resistance to antimicrobials. Continued use of antibiotics in the treatment and prevention of diseases of dairy cows will continue to be scrutinized. It is clear that strategies employing the prudent use of antimicrobials are needed. This clearly illustrates the importance of effective herd disease prevention and control programs. Based on studies published to date, scientific evidence does not support widespread, emerging resistance among mastitis pathogens to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in dairy cows can contribute to increased antimicrobial resistance. While antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics for the treatment of mastitis far outweigh the disadvantages. The clinical consequences of antimicrobial resistance of dairy pathogens affecting humans appear small. Antimicrobial resistance among dairy pathogens, particularly those found in milk, is likely not a human health concern as long as the milk is pasteurized. However, there are an increasing number of people who choose to consume raw milk. Transmission of an antimicrobial-resistant mastitis pathogen and/or foodborne pathogen to humans could occur if contaminated unpasteurized milk is consumed, which is another important reason why people should not consume raw milk. Likewise, resistant bacteria contaminating meat from dairy cows should not be a significant human health concern if the meat is cooked properly. Prudent use of antibiotics in the dairy industry is important, worthwhile, and necessary. Use of antibiotics at times when animals are susceptible to new infection such as the dry period is a sound management decision and a prudent use of antibiotics on the farm. Strategies involving prudent use of antibiotics for treatment encompass identification of the pathogen causing the infection, determining the susceptibility/resistance of the pathogen to assess the most appropriate antibiotic to use for treatment, and a sufficient treatment duration to ensure effective concentrations of the antibiotic to eliminate the pathogen. As the debate on the use of antibiotics in animal agriculture continues, we need to consider the consequences of, “What would happen if antibiotics are banned for use in the dairy industry and in other food-producing animals?” The implications of this question are far reaching and include such aspects as animal welfare, health, and well-being and impacts on food quantity, quality, and food costs. This question should be an important aspect in this ongoing and controversial debate! PMID:22664201

  7. APDS: Autonomous Pathogen Detection System

    SciTech Connect

    Langlois, R G; Brown, S; Burris, L; Colston, B; Jones, L; Makarewicz, T; Mariella, R; Masquelier, D; McBride, M; Milanovich, F; Masarabadi, S; Venkateswaran, K; Marshall, G; Olson, D; Wolcott, D

    2002-02-14

    An early warning system to counter bioterrorism, the Autonomous Pathogen Detection System (APDS) continuously monitors the environment for the presence of biological pathogens (e.g., anthrax) and once detected, it sounds an alarm much like a smoke detector warns of a fire. Long before September 11, 2001, this system was being developed to protect domestic venues and events including performing arts centers, mass transit systems, major sporting and entertainment events, and other high profile situations in which the public is at risk of becoming a target of bioterrorist attacks. Customizing off-the-shelf components and developing new components, a multidisciplinary team developed APDS, a stand-alone system for rapid, continuous monitoring of multiple airborne biological threat agents in the environment. The completely automated APDS samples the air, prepares fluid samples in-line, and performs two orthogonal tests: immunoassay and nucleic acid detection. When compared to competing technologies, APDS is unprecedented in terms of flexibility and system performance.

  8. Innate Defense against Fungal Pathogens.

    PubMed

    Drummond, Rebecca A; Gaffen, Sarah L; Hise, Amy G; Brown, Gordon D

    2014-11-10

    Human fungal infections have been on the rise in recent years and proved increasingly difficult to treat as a result of the lack of diagnostics, effective antifungal therapies, and vaccines. Most pathogenic fungi do not cause disease unless there is a disturbance in immune homeostasis, which can be caused by modern medical interventions, disease-induced immunosuppression, and naturally occurring human mutations. The innate immune system is well equipped to recognize and destroy pathogenic fungi through specialized cells expressing a broad range of pattern recognition receptors (PRRs). This review will outline the cells and PRRs required for effective antifungal immunity, with a special focus on the major antifungal cytokine IL-17 and recently characterized antifungal inflammasomes. PMID:25384766

  9. Lagenidium giganteum Pathogenicity in Mammals

    PubMed Central

    Vilela, Raquel; Taylor, John W.; Walker, Edward D.

    2015-01-01

    Infections of mammals by species in the phylum Oomycota taxonomically and molecularly similar to known Lagenidium giganteum strains have increased. During 2013–2014, we conducted a phylogenetic study of 21 mammalian Lagenidium isolates; we found that 11 cannot be differentiated from L. giganteum strains that the US Environmental Protection Agency approved for biological control of mosquitoes; these strains were later unregistered and are no longer available. L. giganteum strains pathogenic to mammals formed a strongly supported clade with the biological control isolates, and both types experimentally infected mosquito larvae. However, the strains from mammals grew well at 25°C and 37°C, whereas the biological control strains developed normally at 25°C but poorly at higher temperatures. The emergence of heat-tolerant strains of L. giganteum pathogenic to lower animals and humans is of environmental and public health concern. PMID:25625190

  10. Emerging Pathogens in WaterEmerging Pathogens in Water WorkshopWorkshop

    E-print Network

    Fay, Noah

    Emerging Pathogens in WaterEmerging Pathogens in Water WorkshopWorkshop "Coping with Unregulated Pathogens" March 9, 2010 Daniel R. Quintanar, Project Manager, Tucson Water Cynthia Garcia, Environmental Quality Assurance Officer, City of Peoria #12;Naegleria FowleriNaegleria Fowleri ­­ Emerging Pathogen

  11. Animal Pathogen/Product Import Importing "Animal" Pathogens from Outside Canada

    E-print Network

    Animal Pathogen/Product Import Importing "Animal" Pathogens from Outside Canada 1) Permits) Complete the three-page "Facility Certification for the Importation of Animal Pathogens" located the appropriate checklist and complete it. Complete only one of either the "Inspection Checklist ­ Animal Pathogen

  12. Macropinocytosis: a pathway to protozoan infection

    PubMed Central

    de Carvalho, Tecia M. U.; Barrias, Emile S.; de Souza, Wanderley

    2015-01-01

    Among the various endocytic mechanisms in mammalian cells, macropinocytosis involves internalization of large amounts of plasma membrane together with extracellular medium, leading to macropinosome formation. These structures are formed when plasma membrane ruffles are assembled after actin filament rearrangement. In dendritic cells, macropinocytosis has been reported to play a role in antigen presentation. Several intracellular pathogens are internalized by host cells via multiple endocytic pathways and macropinocytosis has been described as an important entry site for various organisms. Some bacteria, such as Legionella pneumophila, as well as various viruses, use this pathway to penetrate and subvert host cells. Some protozoa, which are larger than bacteria and virus, can also use this pathway to invade host cells. As macropinocytosis is characterized by the formation of large uncoated vacuoles and is triggered by various signaling pathways, which is similar to what occurs during the formation of the majority of parasitophorous vacuoles, it is believed that this phenomenon may be more widely used by parasites than is currently appreciated. Here we review protozoa host cell invasion via macropinocytosis.

  13. Bacteriophage-Based Pathogen Detection

    Microsoft Academic Search

    Steven Ripp

    2010-01-01

    \\u000a Considered the most abundant organism on Earth, at a population approaching 1031, bacteriophage, or phage for short, mediate interactions with myriad bacterial hosts that has for decades been exploited\\u000a in phage typing schemes for signature identification of clinical, food-borne, and water-borne pathogens. With over 5,000 phage\\u000a being morphologically characterized and grouped as to susceptible host, there exists an enormous cache

  14. Molecular Epidemiology of Foodborne Pathogens

    Microsoft Academic Search

    Yi Chen; Eric Brown; Stephen J. Knabel

    2011-01-01

    \\u000a The purpose of this chapter is to describe the basic principles and advancements in the molecular epidemiology of foodborne\\u000a pathogens. Epidemiology is the study of the distribution and determinants of infectious diseases and\\/or the dynamics of disease\\u000a transmission. The goals of epidemiology include the identification of physical sources, routes of transmission of infectious\\u000a agents, and distribution and relationships of different

  15. Perturbation of host ubiquitin systems by plant pathogen/pest effector proteins

    PubMed Central

    Banfield, Mark J

    2015-01-01

    Microbial pathogens and pests of animals and plants secrete effector proteins into host cells, altering cellular physiology to the benefit of the invading parasite. Research in the past decade has delivered significant new insights into the molecular mechanisms of how these effector proteins function, with a particular focus on modulation of host immunity-related pathways. One host system that has emerged as a common target of effectors is the ubiquitination system in which substrate proteins are post-translationally modified by covalent conjugation with the small protein ubiquitin. This modification, typically via isopeptide bond formation through a lysine side chain of ubiquitin, can result in target degradation, relocalization, altered activity or affect protein–protein interactions. In this review, I focus primarily on how effector proteins from bacterial and filamentous pathogens of plants and pests perturb host ubiquitination pathways that ultimately include the 26S proteasome. The activities of these effectors, in how they affect ubiquitin pathways in plants, reveal how pathogens have evolved to identify and exploit weaknesses in this system that deliver increased pathogen fitness. PMID:25339602

  16. Pathogen ‘Roid Rage: Cholesterol Utilization by Mycobacterium tuberculosis

    PubMed Central

    Wipperman, Matthew F.; Sampson, Nicole S.; Thomas, Suzanne, T.

    2014-01-01

    The ability of science and medicine to control the pathogen Mycobacterium tuberculosis (Mtb) requires an understanding of the complex host environment within which it resides. Pathological and biological evidence overwhelmingly demonstrate how the mammalian steroid cholesterol is present throughout the course of infection. Better understanding Mtb requires a more complete understanding of how it utilizes molecules like cholesterol in this environment to sustain the infection of the host. Cholesterol uptake, catabolism, and broader utilization are important for maintenance of the pathogen in the host and it has been experimentally validated to contribute to virulence and pathogenesis. Cholesterol is catabolized by at least three distinct sub-pathways, two for the ring system and one for the side chain, yielding dozens of steroid intermediates with varying biochemical properties. Our ability to control this worldwide infectious agent requires a greater knowledge of how Mtb uses cholesterol to its advantage throughout the course of infection. Herein, the current state of knowledge of cholesterol metabolism by Mtb is reviewed from a biochemical perspective with a focus on the metabolic genes and pathways responsible for cholesterol steroid catabolism. PMID:24611808

  17. Modulation of Tumor Necrosis Factor by Microbial Pathogens

    PubMed Central

    Rahman, Masmudur M; McFadden, Grant

    2006-01-01

    In response to invasion by microbial pathogens, host defense mechanisms get activated by both the innate and adaptive arms of the immune responses. TNF (tumor necrosis factor) is a potent proinflammatory cytokine expressed by activated macrophages and lymphocytes that induces diverse cellular responses that can vary from apoptosis to the expression of genes involved in both early inflammatory and acquired immune responses. A wide spectrum of microbes has acquired elegant mechanisms to overcome or deflect the host responses mediated by TNF. For example, modulatory proteins encoded by multiple families of viruses can block TNF and TNF-mediated responses at multiple levels, such as the inhibition of the TNF ligand or its receptors, or by modulating key transduction molecules of the TNF signaling pathway. Bacteria, on the other hand, tend to modify TNF-mediated responses specifically by regulating components of the TNF signaling pathway. Investigation of these diverse strategies employed by viral and bacterial pathogens has significantly advanced our understanding of both host TNF responses and microbial pathogenesis. This review summarizes the diverse microbial strategies to regulate TNF and how such insights into TNF modulation could benefit the treatment of inflammatory or autoimmune diseases. PMID:16518473

  18. Fructooligosacharides Reduce Pseudomonas aeruginosa PAO1 Pathogenicity through Distinct Mechanisms

    PubMed Central

    Ortega-González, Mercedes; Sánchez de Medina, Fermín; Molina-Santiago, Carlos; López-Posadas, Rocío; Pacheco, Daniel; Krell, Tino; Martínez-Augustin, Olga; Abdelali, Daddaoua

    2014-01-01

    Pseudomonas aeruginosa is ubiquitously present in the environment and acts as an opportunistic pathogen on humans, animals and plants. We report here the effects of the prebiotic polysaccharide inulin and its hydrolysed form FOS on this bacterium. FOS was found to inhibit bacterial growth of strain PAO1, while inulin did not affect growth rate or yield in a significant manner. Inulin stimulated biofilm formation, whereas a dramatic reduction of the biofilm formation was observed in the presence of FOS. Similar opposing effects were observed for bacterial motility, where FOS inhibited the swarming and twitching behaviour whereas inulin caused its stimulation. In co-cultures with eukaryotic cells (macrophages) FOS and, to a lesser extent, inulin reduced the secretion of the inflammatory cytokines IL-6, IL-10 and TNF-?. Western blot experiments indicated that the effects mediated by FOS in macrophages are associated with a decreased activation of the NF-?B pathway. Since FOS and inulin stimulate pathway activation in the absence of bacteria, the FOS mediated effect is likely to be of indirect nature, such as via a reduction of bacterial virulence. Further, this modulatory effect is observed also with the highly virulent ptxS mutated strain. Co-culture experiments of P. aeruginosa with IEC18 eukaryotic cells showed that FOS reduces the concentration of the major virulence factor, exotoxin A, suggesting that this is a possible mechanism for the reduction of pathogenicity. The potential of these compounds as components of antibacterial and anti-inflammatory cocktails is discussed. PMID:24465697

  19. Minisequencing mitochondrial DNA pathogenic mutations

    PubMed Central

    Álvarez-Iglesias, Vanesa; Barros, Francisco; Carracedo, Ángel; Salas, Antonio

    2008-01-01

    Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA) diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain) patients carrying haplogroup J lineages (Fisher's Exact test, P-value < 0.01). The assay performs well in mixture experiments of wild:mutant DNAs that emulate heteroplasmic conditions in mtDNA diseases. Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories. PMID:18402672

  20. Emerging water-borne pathogens.

    PubMed

    Sharma, S; Sachdeva, P; Virdi, J S

    2003-06-01

    Emerging water-borne pathogens constitute a major health hazard in both developed and developing nations. A new dimension to the global epidemiology of cholera-an ancient scourge-was provided by the emergence of Vibrio cholerae O139. Also, water-borne enterohaemorrhagic Escherichia coli ( E. coli O157:H7), although regarded as a problem of the industrialized west, has recently caused outbreaks in Africa. Outbreaks of chlorine-resistant Cryptosporidium have motivated water authorities to reassess the adequacy of current water-quality regulations. Of late, a host of other organisms, such as hepatitis viruses (including hepatitis E virus), Campylobacter jejuni, microsporidia, cyclospora, Yersinia enterocolitica, calciviruses and environmental bacteria like Mycobacterium spp, aeromonads, Legionella pneumophila and multidrug-resistant Pseudomonas aeruginosa have been associated with water-borne illnesses. This review critically examines the potential of these as emerging water-borne pathogens. It also examines the possible reasons, such as an increase in the number of immunocompromised individuals, urbanization and horizontal gene transfer, that may underlie their emergence. Further, measures required to face the challenge posed by these pathogens are also discussed. PMID:12684849

  1. Mapping population and pathogen movements

    PubMed Central

    Tatem, Andrew J.

    2014-01-01

    For most of human history, populations have been relatively isolated from each other, and only recently has there been extensive contact between peoples, flora and fauna from both old and new worlds. The reach, volume and speed of modern travel are unprecedented, with human mobility increasing in high income countries by over 1000-fold since 1800. This growth is putting people at risk from the emergence of new strains of familiar diseases, and from completely new diseases, while ever more cases of the movement of both disease vectors and the diseases they carry are being seen. Pathogens and their vectors can now move further, faster and in greater numbers than ever before. Equally however, we now have access to the most detailed and comprehensive datasets on human mobility and pathogen distributions ever assembled, in order to combat these threats. This short review paper provides an overview of these datasets, with a particular focus on low income regions, and covers briefly approaches used to combine them to help us understand and control some of the negative effects of population and pathogen movements. PMID:24480992

  2. Mapping population and pathogen movements.

    PubMed

    Tatem, Andrew J

    2014-03-01

    For most of human history, populations have been relatively isolated from each other, and only recently has there been extensive contact between peoples, flora and fauna from both old and new worlds. The reach, volume and speed of modern travel are unprecedented, with human mobility increasing in high income countries by over 1000-fold since 1800. This growth is putting people at risk from the emergence of new strains of familiar diseases, and from completely new diseases, while ever more cases of the movement of both disease vectors and the diseases they carry are being seen. Pathogens and their vectors can now move further, faster and in greater numbers than ever before. Equally however, we now have access to the most detailed and comprehensive datasets on human mobility and pathogen distributions ever assembled, in order to combat these threats. This short review paper provides an overview of these datasets, with a particular focus on low income regions, and covers briefly approaches used to combine them to help us understand and control some of the negative effects of population and pathogen movements. PMID:24480992

  3. Molecular Mechanisms of Bacterial Pathogenicity

    NASA Astrophysics Data System (ADS)

    Fuchs, Thilo Martin

    Cautious optimism has arisen over recent decades with respect to the long struggle against bacteria, viruses, and parasites. This has been offset, however, by a fatal complacency stemming from previous successes such as the development of antimicrobial drugs, the eradication of smallpox, and global immunization programs. Infectious diseases nevertheless remain the world's leading cause of death, killing at least 17 million persons annually [61]. Diarrheal diseases caused by Vibrio cholerae or Shigella dysenteriae kill about 3 million persons every year, most of them young children: Another 4 million die of tuberculosis or tetanus. Outbreaks of diphtheria in Eastern Europe threatens the population with a disease that had previously seemed to be overcome. Efforts to control infectious diseases more comprehensively are undermined not only by socioeconomic conditions but also by the nature of the pathogenic organisms itself; some isolates of Staphylococcus aureus and Enterobacter have become so resistant to drugs by horizontal gene transfer that they are almost untreatable. In addition, the mechanism of genetic variability helps pathogens to evade the human immune system, thus compromising the development of powerful vaccines. Therefore detailed knowledge of the molecular mechanisms of microbial pathogenicity is absolutely necessary to develop new strategies against infectious diseases and thus to lower their impact on human health and social development.

  4. Pathogens in septage in Vietnam.

    PubMed

    Yen-Phi, Vo Thi; Rechenburg, Andrea; Vinneras, Björn; Clemens, Joachim; Kistemann, Thomas

    2010-04-01

    Septage is widely acknowledged as a major source of infectious pathogens while disposal of septage, and the operation and maintenance of septic tanks, is not regulated in many developing countries. Twenty untreated septage and septage sludge samples were taken from Can Tho City, Vietnam to examine their pathogen content, and indicator micro-organisms. Escherichia coli and Enterococcus spp. were detected in all samples, regardless of sludge storage time. Phages were detected in 80% of samples. Salmonella spp. were detected in 70% of the untreated septage and 60% of septage sludge samples. Concentrations of phages and bacteria tested in septage sludge after many years of tank storage were much higher than the expected levels. Helminth ova were present in 95% of untreated septage samples with an average of 450 oval(-1), and were detected in all septage sludge samples with an average of 16,000 oval(-1). Twelve varieties of helminth ova were identified. More helminth ova varieties in higher concentrations were found in septage than those reported from stool samples. The varieties' frequency ranged from 10% to 50% and Ascaris lumbricoides predominated. Results show that pathogens and indicator micro-organisms, especially helminth ova, accumulate in sludge. Thus helminth ova should be considered when septage sludge is treated and used for agriculture. Proper health protection measures must be applied for people handling septage. PMID:20138647

  5. Pathogenic Ubqln2 gains toxic properties to induce neuron death.

    PubMed

    Wu, Qinxue; Liu, Mujun; Huang, Cao; Liu, Xionghao; Huang, Bo; Li, Niansheng; Zhou, Hongxia; Xia, Xu-Gang

    2015-03-01

    Mutations in ubiquilin 2 (Ubqln2) is linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration. A foremost question regarding Ubqln2 pathogenesis is whether pathogenically mutated Ubqln2 causes neuron death via a gain or loss of functions. To better understand Ubqln2 pathobiology, we created Ubqln2 transgenic and knockout rats and compared phenotypic expression in these novel rat models. Overexpression of Ubqln2 with a pathogenic mutation (P497H substitution) caused cognitive deficits and neuronal loss in transgenic rats at the age of 130 days. In the transgenic rats, neuronal loss was preceded by the progressive formation of Ubqln2 aggregates and was accompanied by the progressive accumulation of the autophagy substrates p62 and LC3-II and the impairment of endosome pathways. In contrast, none of these pathologies observed in mutant Ubqln2 transgenic rats was detected in Ubqln2 knockout rats at the age of 300 days. Together, our findings in Ubqln2 transgenic and knockout rats collectively suggest that pathogenic Ubqln2 causes neuron death mainly through a gain of unrevealed functions rather than a loss of physiological functions. PMID:25388785

  6. Review Article Molecular Pathways of Protein Synthesis Inhibition During

    E-print Network

    DeGracia, Donald J.

    -12, and CHOP transcription). Sus- tained eIF2( P) is proapoptotic by inducing the synthesis of ATF4, the CHOP transcription factor, through "bypass scan- ning" of 5 upstream open-reading frames in ATF4 messenger RNA; these upstream open-reading frames normally inhibit ac- cess to the ATF4 coding sequence

  7. Fluorene Degradation Pathway Map

    NSDL National Science Digital Library

    Feng, Jingfeng.

    The University of Minnesota Biocatalysis/Biodegradation Database (UM/BBD) contains "microbial biocatalytic reactions and biodegradation pathways primarily for xenobiotic, chemical compounds." A new microbial enzyme-catalyzed reactions has been posted for Flourene. Flourene is commonly found in vehicle exhaust emissions, motor oils, crude oils, coal and oil combustion products, industrial effluents, and waste incineration, and is a major component of "fossil fuels and their derivatives." The Fluorene pathway map includes organisms which initiate the pathway, as well as organisms that carry out later steps. The pathway map provides detailed information on each hyperlinked step, including graphics, product/substrate reactions, and external links to further information.

  8. Epigenetic control of effectors in plant pathogens

    PubMed Central

    Gijzen, Mark; Ishmael, Chelsea; Shrestha, Sirjana D.

    2014-01-01

    Plant pathogens display impressive versatility in adapting to host immune systems. Pathogen effector proteins facilitate disease but can become avirulence (Avr) factors when the host acquires discrete recognition capabilities that trigger immunity. The mechanisms that lead to changes to pathogen Avr factors that enable escape from host immunity are diverse, and include epigenetic switches that allow for reuse or recycling of effectors. This perspective outlines possibilities of how epigenetic control of Avr effector gene expression may have arisen and persisted in filamentous plant pathogens, and how it presents special problems for diagnosis and detection of specific pathogen strains or pathotypes. PMID:25429296

  9. Contribution of Small RNA Pathway Components in Plant Immunity

    PubMed Central

    Seo, Jang-Kyun; Wu, Jianguo; Lii, Yifan; Li, Yi; Jin, Hailing

    2013-01-01

    Small RNAs regulate a multitude of cellular processes, including development, stress responses, metabolism, and maintenance of genome integrity, in a sequence-specific manner. Accumulating evidence reveals that host endogenous small RNAs and small RNA pathway components play important roles in plant immune responses against various pathogens, including bacteria, fungi, oomycetes, and viruses. Small-RNA-mediated defense responses are regulated through diverse pathways and the components of these pathways, including Dicer-like proteins, RNA-dependent RNA polymerases, Argonaute proteins, and RNA polymerase IV and V, exhibit functional specificities as well as redundancy. In this review, we summarize the recent insights revealed mainly through the examination of two model plants, Arabidopsis and rice, with a primary focus on our emerging understanding of how these small RNA pathway components contribute to plant immunity. PMID:23489060

  10. Contamination of water resources by pathogenic bacteria

    PubMed Central

    2014-01-01

    Water-borne pathogen contamination in water resources and related diseases are a major water quality concern throughout the world. Increasing interest in controlling water-borne pathogens in water resources evidenced by a large number of recent publications clearly attests to the need for studies that synthesize knowledge from multiple fields covering comparative aspects of pathogen contamination, and unify them in a single place in order to present and address the problem as a whole. Providing a broader perceptive of pathogen contamination in freshwater (rivers, lakes, reservoirs, groundwater) and saline water (estuaries and coastal waters) resources, this review paper attempts to develop the first comprehensive single source of existing information on pathogen contamination in multiple types of water resources. In addition, a comprehensive discussion describes the challenges associated with using indicator organisms. Potential impacts of water resources development on pathogen contamination as well as challenges that lie ahead for addressing pathogen contamination are also discussed. PMID:25006540

  11. Contamination of water resources by pathogenic bacteria.

    PubMed

    Pandey, Pramod K; Kass, Philip H; Soupir, Michelle L; Biswas, Sagor; Singh, Vijay P

    2014-01-01

    Water-borne pathogen contamination in water resources and related diseases are a major water quality concern throughout the world. Increasing interest in controlling water-borne pathogens in water resources evidenced by a large number of recent publications clearly attests to the need for studies that synthesize knowledge from multiple fields covering comparative aspects of pathogen contamination, and unify them in a single place in order to present and address the problem as a whole. Providing a broader perceptive of pathogen contamination in freshwater (rivers, lakes, reservoirs, groundwater) and saline water (estuaries and coastal waters) resources, this review paper attempts to develop the first comprehensive single source of existing information on pathogen contamination in multiple types of water resources. In addition, a comprehensive discussion describes the challenges associated with using indicator organisms. Potential impacts of water resources development on pathogen contamination as well as challenges that lie ahead for addressing pathogen contamination are also discussed. PMID:25006540

  12. Pathogenicity of fowl adenovirus in specific pathogen free chicken embryos.

    PubMed

    Alemnesh, W; Hair-Bejo, M; Aini, I; Omar, A R

    2012-01-01

    Inclusion body hepatitis (IBH) associated with fowl adenovirus (FAdV) infection has a worldwide distribution. The aim of the present study was to determine the pathogenicity of Malaysian FAdV serotype 9 (UPM04217) in specific pathogen free (SPF) embryonated chicken embryos. FAdV (titre 10(5.8)/ml) was inoculated into SPF embryonated chicken eggs (0.1 ml per egg) via the chorioallantoic membrane (CAM). There was 100% embryo mortality within 4-11 days post infection (dpi). The gross and microscopical lesions of the embryo were confined to the liver and were noted at 5, 7, 9 and 11 dpi. The liver was pale with multifocal areas of necrosis, fibrosis and haemorrhage. Microscopically, there was moderate to severe congestion and haemorrhage and severe and diffuse hepatocyte degeneration and necrosis, with intranuclear inclusion bodies (INIBs) and associated inflammation. Haemorrhage, congestion, degeneration, necrosis and hyperplasia of the CAM with INIBs were observed at 5, 7, 9 and 11 dpi. Varying degrees of congestion, haemorrhage, degeneration and necrosis were also observed in the yolk sac, kidney, spleen, heart and bursa of Fabricius. Ultrastructurally, numerous viral particles in the nucleus of hepatocytes were recorded at 7, 9 and 11 dpi, whereas at 5 dpi, fine granular and filamentous INIBs were observed. The INIBs in the CAM were present either as fine granular filamentous structures or as large viral inclusions. FAdV (UPM04217) is therefore highly pathogenic to SPF chicken embryos and the embryonic liver should be used for isolation and propagation of the virus. PMID:21705014

  13. Including pathogen risk in life cycle assessment of wastewater management. 2. Quantitative comparison of pathogen risk to other impacts on human health.

    PubMed

    Heimersson, Sara; Harder, Robin; Peters, Gregory M; Svanström, Magdalena

    2014-08-19

    Resource recovery from sewage sludge has the potential to save natural resources, but the potential risks connected to human exposure to heavy metals, organic micropollutants, and pathogenic microorganisms attract stakeholder concern. The purpose of the presented study was to include pathogen risks to human health in life cycle assessment (LCA) of wastewater and sludge management systems, as this is commonly omitted from LCAs due to methodological limitations. Part 1 of this article series estimated the overall pathogen risk for such a system with agricultural use of the sludge, in a way that enables the results to be integrated in LCA. This article (part 2) presents a full LCA for two model systems (with agricultural utilization or incineration of sludge) to reveal the relative importance of pathogen risk in relation to other potential impacts on human health. The study showed that, for both model systems, pathogen risk can constitute an important part (in this study up to 20%) of the total life cycle impacts on human health (expressed in disability adjusted life years) which include other important impacts such as human toxicity potential, global warming potential, and photochemical oxidant formation potential. PMID:25058416

  14. RESEARCH ARTICLE Open Access Social and cultural dimensions of hygiene in

    E-print Network

    Paris-Sud XI, Université de

    RESEARCH ARTICLE Open Access Social and cultural dimensions of hygiene in Cambodian health care,3 , Sirenda Vong1 Abstract Background: The frequency of bloodborne pathogen healthcare practices; they need to be considered when designing interventions to improve infection control practices

  15. Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi

    PubMed Central

    Taborda, Carlos P.; da Silva, Marcelo B.; Nosanchuk, Joshua D.; Travassos, Luiz R.

    2008-01-01

    Melanin pigments are substances produced by a broad variety of pathogenic microorganisms, including bacteria, fungi, and helminths. Microbes predominantly produce melanin pigment via tyrosinases, laccases, catecholases, and the polyketide synthase pathway. In fungi, melanin is deposited in the cell wall and cytoplasm, and melanin particles (“ghosts”) can be isolated from these fungi that have the same size and shape of the original cells. Melanin has been reported in several human pathogenic dimorphic fungi including Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii. Melanization appears to contribute to virulence by reducing the susceptibility of melanized fungi to host defense mechanisms and antifungal drugs. PMID:18777637

  16. Modulation of Intestinal TLR4-Inflammatory Signaling Pathways by Probiotic Microorganisms: Lessons Learned from Lactobacillus jensenii TL2937

    PubMed Central

    Villena, Julio; Kitazawa, Haruki

    2014-01-01

    The intestinal mucosa plays a critical role in the host’s interactions with innocuous commensal microbiota and invading pathogenic microorganisms. Intestinal epithelial cells (IECs) and gut associated immune cells recognize the bacterial components via pattern-recognition receptors (PRRs) and are responsible for maintaining tolerance to the large communities of resident luminal bacteria while being also able to mount inflammatory responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs that are present on IECs and immune cells which are involved in the induction of both tolerance and inflammation. A growing body of experimental and clinical evidence supports the therapeutic and preventive application of probiotics for several gastrointestinal inflammatory disorders in which?TLRs exert a significant role. This review aims to summarize the current knowledge of the beneficial effects of probiotic microorganisms with the capacity to modulate the immune system (immunobiotics) in the regulation of intestinal inflammation in pigs, which are very important as both livestock and human model. Especially we discuss the role of?TLRs, their signaling pathways, and their negative regulators in both the inflammatory intestinal injury and the beneficial effects of immunobiotics in general, and Lactobacillus jensenii?TL2937 in particular. This review article emphasizes the cellular and molecular interactions of immunobiotics with IECs and immune cells through?TLRs and their application for improving animal and human health. PMID:24459463

  17. Mechanisms and pathways of innate immune activation and regulation in health and cancer.

    PubMed

    Cui, Jun; Chen, Yongjun; Wang, Helen Y; Wang, Rong-Fu

    2014-11-01

    Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer. PMID:25625930

  18. Insect antiviral innate immunity: pathways, effectors, and connections

    PubMed Central

    Kingsolver, Megan B.; Huang, Zhijing; Hardy, Richard W.

    2014-01-01

    Insects are infected by a wide array of viruses some of which are insect-restricted and pathogenic, and some of which are transmitted by biting insects to vertebrates. The medical and economic importance of these viruses heightens the need to understand the interaction between the infecting pathogen and the insect immune system in order to develop transmission interventions. The interaction of the virus with the insect host innate immune system plays a critical role in the outcome of infection. The major mechanism of antiviral defense is the siRNA pathway that responds through the detection of virus-derived dsRNA to suppress virus replication. However, other innate antimicrobial pathways such as Imd, Toll, Jak-STAT, and the autophagy pathway have also been shown to play important roles in antiviral immunity. In this review we provide an overview of the current understanding of the main insect antiviral pathways and examine recent findings that further our understanding of the roles of these pathways in facilitating a systemic and specific response to infecting viruses. PMID:24120681

  19. Building clinical pathways.

    PubMed

    Leininger, S M

    1998-01-01

    TQM principles change the work environment so that point-of-service personnel can improve health care delivery to patients. The clinical pathway process starts with the principles of TQM. In the era of managed care, health care resources can be managed effectively using a clinical pathway. The multidisciplinary team has the opportunity to improve the health care services provided to patients. PMID:9847822

  20. Pathway Logic Carolyn Talcott

    E-print Network

    Breitling, Rainer

    Pathway Logic Carolyn Talcott SRI International 333 Ravenswood Avenue, Menlo Park, CA 94025, USA clt@csl.sri.com Abstract. Pathway Logic (PL) is an approach to modeling and analysis of bio- logical or inhibited by signaling processes. Furthermore, metabolites such as glucose play role in controling signal

  1. Pathway Logic Carolyn Talcott

    E-print Network

    Pathway Logic Carolyn Talcott SRI International 333 Ravenswood Avenue, Menlo Park, CA 94025, USA clt@csl.sri.com Abstract. Pathway Logic (PL) is an approach to modeling and analysis of bio- logical or inhibited by signaling processes. Furthermore, metabolites such as glucose play a role in controlling signal

  2. Pathways with Friends

    NSDL National Science Digital Library

    Christian Davies

    2008-01-01

    Directed by instructional cards, learners kinesthetically model cell communication by acting as components in a cell signaling pathway. Learners discover that cell communication is a multi-step process and that cells communicate via signaling pathways made of interacting components that sometimes change shape as a result of their interaction (conformational change).

  3. Career Pathways in Indiana

    ERIC Educational Resources Information Center

    McCaskey, Steve; Johnson, Tricia

    2010-01-01

    The revisions to the Carl D. Perkins Career and Technical Education Act of 2006 require that career and technical education (CTE) programs provide students with a clear pathway from secondary to postsecondary education, and into high-wage, high-skill and high-demand careers. States nationwide are developing programs, called career pathways, to…

  4. The intrinsic resistome of bacterial pathogens

    PubMed Central

    Olivares, Jorge; Bernardini, Alejandra; Garcia-Leon, Guillermo; Corona, Fernando; B. Sanchez, Maria; Martinez, Jose L.

    2013-01-01

    Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice. PMID:23641241

  5. The Genus Aeromonas: Taxonomy, Pathogenicity, and Infection

    PubMed Central

    Janda, J. Michael; Abbott, Sharon L.

    2010-01-01

    Summary: Over the past decade, the genus Aeromonas has undergone a number of significant changes of practical importance to clinical microbiologists and scientists alike. In parallel with the molecular revolution in microbiology, several new species have been identified on a phylogenetic basis, and the genome of the type species, A. hydrophila ATCC 7966, has been sequenced. In addition to established disease associations, Aeromonas has been shown to be a significant cause of infections associated with natural disasters (hurricanes, tsunamis, and earthquakes) and has been linked to emerging or new illnesses, including near-drowning events, prostatitis, and hemolytic-uremic syndrome. Despite these achievements, issues still remain regarding the role that Aeromonas plays in bacterial gastroenteritis, the extent to which species identification should be attempted in the clinical laboratory, and laboratory reporting of test results from contaminated body sites containing aeromonads. This article provides an extensive review of these topics, in addition to others, such as taxonomic issues, microbial pathogenicity, and antimicrobial resistance markers. PMID:20065325

  6. APDS: The Autonomous Pathogen Detection System

    SciTech Connect

    Hindson, B; Makarewicz, A; Setlur, U; Henderer, B; McBride, M; Dzenitis, J

    2004-10-04

    We have developed and tested a fully autonomous pathogen detection system (APDS) capable of continuously monitoring the environment for airborne biological threat agents. The system was developed to provide early warning to civilians in the event of a bioterrorism incident and can be used at high profile events for short-term, intensive monitoring or in major public buildings or transportation nodes for long-term monitoring. The APDS is completely automated, offering continuous aerosol sampling, in-line sample preparation fluidics, multiplexed detection and identification immunoassays, and nucleic-acid based polymerase chain reaction (PCR) amplification and detection. Highly multiplexed antibody-based and duplex nucleic acid-based assays are combined to reduce false positives to a very low level, lower reagent costs, and significantly expand the detection capabilities of this biosensor. This article provides an overview of the current design and operation of the APDS. Certain sub-components of the ADPS are described in detail, including the aerosol collector, the automated sample preparation module that performs multiplexed immunoassays with confirmatory PCR, and the data monitoring and communications system. Data obtained from an APDS that operated continuously for seven days in a major U.S. transportation hub is reported.

  7. Immune pathways and defence mechanisms in honey bees Apis mellifera

    PubMed Central

    Evans, J D; Aronstein, K; Chen, Y P; Hetru, C; Imler, J-L; Jiang, H; Kanost, M; Thompson, G J; Zou, Z; Hultmark, D

    2006-01-01

    Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens. PMID:17069638

  8. ArticleLinker ArticleLinker

    E-print Network

    Takada, Shoji

    (Free Article), Google : KULINE : : PubMed, Scopus, CiNii, Webcat Plus, Impact Factor, RefWorks ArticleDiscus, CAB Abstracts, Global Health, AGRIS, AGRICOLA, MEDLINE(Ovid ), Evidence Based Medicine Reviews, CINAHL

  9. Identification of virulence associated loci in the emerging broad host range plant pathogen Pseudomonas fuscovaginae.

    PubMed

    Patel, Hitendra; Matiuzzo, Maura; Bertani, Iris; Bigirimana, Vincent; Ash, Gavin J; Höfte, Monica; Venturi, Vittorio

    2014-11-14

    Background Pseudomonas fuscovaginae (Pfv) is an emerging plant pathogen of rice and also of other gramineae plants. It causes sheath brown rot disease in rice with symptoms that are characterized by brown lesions on the flag leaf sheath, grain discoloration and sterility. It was first isolated as a high altitude pathogen in Japan and has since been reported in several countries throughout the world. Pfv is a broad host range pathogen and very little is known about its virulence mechanisms.ResultsAn in planta screen of 1000 random independent Tn5 genomic mutants resulted in the isolation of nine mutants which showed altered virulence. Some of these isolates are mutated for functions which are known to be virulence associated factors in other phytopathogenic bacteria (eg. pil gene, phytotoxins and T6SS) and others might represent novel virulence loci.ConclusionsBeing an emerging pathogen worldwide, the broad host range pathogen Pfv has not yet been studied for its virulence functions. The roles of the nine loci identified in the in planta screen are discussed in relation to pathogenicity of Pfv. In summary, this article reports a first study on the virulence of this pathogen involving in planta screening studies and suggests the presence of several virulence features with known and novel functions in the Pseudomonas group of bacteria. PMID:25394860

  10. The Autonomous Pathogen Detection System

    SciTech Connect

    Dzenitis, J M; Makarewicz, A J

    2009-01-13

    We developed, tested, and now operate a civilian biological defense capability that continuously monitors the air for biological threat agents. The Autonomous Pathogen Detection System (APDS) collects, prepares, reads, analyzes, and reports results of multiplexed immunoassays and multiplexed PCR assays using Luminex{copyright} xMAP technology and flow cytometer. The mission we conduct is particularly demanding: continuous monitoring, multiple threat agents, high sensitivity, challenging environments, and ultimately extremely low false positive rates. Here, we introduce the mission requirements and metrics, show the system engineering and analysis framework, and describe the progress to date including early development and current status.

  11. Molecular Epidemiology of Foodborne Pathogens

    NASA Astrophysics Data System (ADS)

    Chen, Yi; Brown, Eric; Knabel, Stephen J.

    The purpose of this chapter is to describe the basic principles and advancements in the molecular epidemiology of foodborne pathogens. Epidemiology is the study of the distribution and determinants of infectious diseases and/or the dynamics of disease transmission. The goals of epidemiology include the identification of physical sources, routes of transmission of infectious agents, and distribution and relationships of different subgroups. Molecular epidemiology is the study of epidemiology at the molecular level. It has been defined as "a science that focuses on the contribution of potential genetic and environmental risk factors, identified at the molecular level, to the etiology, distribution and prevention of diseases within families and across populations".

  12. Latent Tuberculosis: Models, Computational Efforts and the Pathogen's Regulatory Mechanisms during Dormancy.

    PubMed

    Magombedze, Gesham; Dowdy, David; Mulder, Nicola

    2013-01-01

    Latent tuberculosis is a clinical syndrome that occurs after an individual has been exposed to the Mycobacterium tuberculosis (Mtb) Bacillus, the infection has been established and an immune response has been generated to control the pathogen and force it into a quiescent state. Mtb can exit this quiescent state where it is unresponsive to treatment and elusive to the immune response, and enter a rapid replicating state, hence causing infection reactivation. It remains a gray area to understand how the pathogen causes a persistent infection and it is unclear whether the organism will be in a slow replicating state or a dormant non-replicating state. The ability of the pathogen to adapt to changing host immune response mechanisms, in which it is exposed to hypoxia, low pH, nitric oxide (NO), nutrient starvation, and several other anti-microbial effectors, is associated with a high metabolic plasticity that enables it to metabolize under these different conditions. Adaptive gene regulatory mechanisms are thought to coordinate how the pathogen changes their metabolic pathways through mechanisms that sense changes in oxygen tension and other stress factors, hence stimulating the pathogen to make necessary adjustments to ensure survival. Here, we review studies that give insights into latency/dormancy regulatory mechanisms that enable infection persistence and pathogen adaptation to different stress conditions. We highlight what mathematical and computational models can do and what they should do to enhance our current understanding of TB latency. PMID:25023946

  13. Th1/Th2 Paradigm Extended: Macrophage Polarization as an Unappreciated Pathogen-Driven Escape Mechanism?

    PubMed Central

    Muraille, Eric; Leo, Oberdan; Moser, Muriel

    2014-01-01

    The classical view of the Th1/Th2 paradigm posits that the pathogen nature, infectious cycle, and persistence represent key parameters controlling the choice of effector mechanisms operating during an immune response. Thus, efficient Th1 responses are triggered by replicating intracellular pathogens, while Th2 responses would control helminth infection and promote tissue repair during the resolution phase of an infectious event. However, this vision does not account for a growing body of data describing how pathogens exploit the polarization of the host immune response to their own benefit. Recently, the study of macrophages has illustrated a novel aspect of this arm race between pathogens and the immune system, and the central role of macrophages in homeostasis, repair and defense of all tissues is now fully appreciated. Like T lymphocytes, macrophages differentiate into distinct effectors including classically (M1) and alternatively (M2) activated macrophages. Interestingly, in addition to represent immune effectors, M1/M2 cells have been shown to represent potential reservoir cells to a wide range of intracellular pathogens. Subversion of macrophage cell metabolism by microbes appears as a recently uncovered immune escape strategy. Upon infection, several microbial agents have been shown to activate host metabolic pathways leading to the production of nutrients necessary to their long-term persistence in host. The purpose of this review is to summarize and discuss the strategies employed by pathogens to manipulate macrophage differentiation, and in particular their basic cell metabolism, to favor their own growth while avoiding immune control. PMID:25505468

  14. Pathogen inactivation in blood products.

    PubMed

    Wainwright, Mark

    2002-01-01

    A combination of the economic importance of blood as a resource and the advent of the AIDS epidemic has led to a requirement for improved pathogen screening techniques for donated blood. However, due to window periods where infective agents cannot be detected, the ability to disinfect of blood and its derivatives plasma, platelets and red blood cell concentrates has assumed great importance. Whereas conventional disinfection techniques such as solvent-detergent treatment or ultra-violet irradiation may be employed in plasma or protein concentrates, the collateral damage associated with such treatments disallows their use with cellular fractions. In many ways the pathogen selectivity required here is akin to standard antimicrobial chemotherapy but is complicated by the requirement for activity against the full range of microbes--viruses, bacteria, yeasts and protozoa--rather than simply antibacterial or antiviral etc. The recent problems due to prion agents in the blood supply mean that such agents should also be included in any proposed disinfecting regimen. Several new approaches to microbial disinfection have been proposed by academia and the "blood industrials" : targeted chemotherapy, photochemotherapy and photodynamic antimicrobial chemotherapy. PMID:11860353

  15. Pathogenic potential of Campylobacter ureolyticus.

    PubMed

    Burgos-Portugal, Jose A; Kaakoush, Nadeem O; Raftery, Mark J; Mitchell, Hazel M

    2012-02-01

    The recent detection and isolation of the aflagellate Campylobacter ureolyticus (previously known as Bacteroides ureolyticus) from intestinal biopsy specimens and fecal samples of children with newly diagnosed Crohn's disease led us to investigate the pathogenic potential of this bacterium. Adherence and gentamicin protection assays were employed to quantify the levels of adherence to and invasion into host cells. C. ureolyticus UNSWCD was able to adhere to the Caco-2 intestinal epithelial cell line with a value of 5.341% ± 0.74% but was not able to invade the Caco-2 cells. The addition of two proinflammatory cytokines, tumor necrosis factor alpha (TNF-?) and gamma interferon (IFN-?), to the cell line did not affect attachment or invasion, with attachment levels being 4.156% ± 0.61% (P = 0.270) for TNF-? and 6.472% ± 0.61% (P = 0.235) for IFN-?. Scanning electron microscopy visually confirmed attachment and revealed that C. ureolyticus UNSWCD colonizes and adheres to intestinal cells, inducing cellular damage and microvillus degradation. Purification and identification of the C. ureolyticus UNSWCD secretome detected a total of 111 proteins, from which 29 were bioinformatically predicted to be secretory proteins. Functional classification revealed three putative virulence and colonization factors: the surface antigen CjaA, an outer membrane fibronectin binding protein, and an S-layer RTX toxin. These results suggest that C. ureolyticus has the potential to be a pathogen of the gastrointestinal tract. PMID:22124656

  16. Bacteriophage-Based Pathogen Detection

    NASA Astrophysics Data System (ADS)

    Ripp, Steven

    Considered the most abundant organism on Earth, at a population approaching 1031, bacteriophage, or phage for short, mediate interactions with myriad bacterial hosts that has for decades been exploited in phage typing schemes for signature identification of clinical, food-borne, and water-borne pathogens. With over 5,000 phage being morphologically characterized and grouped as to susceptible host, there exists an enormous cache of bacterial-specific sensors that has more recently been incorporated into novel bio-recognition assays with heightened sensitivity, specificity, and speed. These assays take many forms, ranging from straightforward visualization of labeled phage as they attach to their specific bacterial hosts to reporter phage that genetically deposit trackable signals within their bacterial hosts to the detection of progeny phage or other uniquely identifiable elements released from infected host cells. A comprehensive review of these and other phage-based detection assays, as directed towards the detection and monitoring of bacterial pathogens, will be provided in this chapter.

  17. Enteric pathogens through life stages

    PubMed Central

    Kolling, Glynis; Wu, Martin; Guerrant, Richard L.

    2012-01-01

    Enteric infections and diarrheal diseases constitute pervasive health burdens throughout the world, with rates being highest at the two ends of life. During the first 2–3 years of life, much of the disease burden may be attributed to infection with enteric pathogens including Salmonella, rotavirus, and many other bacterial, viral, and protozoan organisms; however, infections due to Clostridium difficile exhibit steady increases with age. Still others, like Campylobacter infections in industrialized settings are high in early life (<2 years old) and increase again in early adulthood (called the “second weaning” by some). The reasons for these differences undoubtedly reside in part in pathogen differences; however, host factors including the commensal intestinal microbial communities, immune responses (innate and acquired), and age-dependant shifts likely play important roles. Interplay of these factors is illustrated by studies examining changes in human gut microbiota with inflammatory bowel disease and irritable bowel syndrome. Recent gut microbial surveys have indicated dramatic shifts in gut microbial population structure from infants to young adults to the elders. An understanding of the evolution of these factors and their interactions (e.g., how does gut microbiota modulate the “inflamm-aging” process or vice versa) through the human life “cycle” will be important in better addressing and controlling these enteric infections and their consequences for both quality and quantity of life (often assessed as disability adjusted life-years or “DALYs”). PMID:22937528

  18. Population dynamics of a pathogen: the conundrum of vivax malaria.

    PubMed

    McQueen, Philip G

    2010-08-01

    Building a mathematical model of population dynamics of pathogens within their host involves considerations of factors similar to those in ecology, as pathogens can prey on cells in the host. But within the multicellular host, attacked cell types are integrated with other cellular systems, which in turn intervene in the infection. For example, immune responses attempt to sense and then eliminate or contain pathogens, and homeostatic mechanisms try to compensate for cell loss. This review focuses on modeling applied to malarias, diseases caused by single-cell eukaryote parasites that infect red blood cells, with special concern given to vivax malaria, a disease often thought to be benign (if sometimes incapacitating) because the parasite only attacks a small proportion of red blood cells, the very youngest ones. However, I will use mathematical modeling to argue that depletion of this pool of red blood cells can be disastrous to the host if growth of the parasite is not vigorously check by host immune responses. Also, modeling can elucidate aspects of new field observations that indicate that vivax malaria is more dangerous than previously thought. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12551-010-0034-3) contains supplementary material, which is available to authorized users. PMID:20730124

  19. Unconventionally secreted effectors of two filamentous pathogens target plant salicylate biosynthesis.

    PubMed

    Liu, Tingli; Song, Tianqiao; Zhang, Xiong; Yuan, Hongbo; Su, Liming; Li, Wanlin; Xu, Jing; Liu, Shiheng; Chen, Linlin; Chen, Tianzi; Zhang, Meixiang; Gu, Lichuan; Zhang, Baolong; Dou, Daolong

    2014-01-01

    Plant diseases caused by fungi and oomycetes pose an increasing threat to food security and ecosystem health worldwide. These filamentous pathogens, while taxonomically distinct, modulate host defense responses by secreting effectors, which are typically identified based on the presence of signal peptides. Here we show that Phytophthora sojae and Verticillium dahliae secrete isochorismatases (PsIsc1 and VdIsc1, respectively) that are required for full pathogenesis. PsIsc1 and VdIsc1 can suppress salicylate-mediated innate immunity in planta and hydrolyse isochorismate in vitro. A conserved triad of catalytic residues is essential for both functions. Thus, the two proteins are isochorismatase effectors that disrupt the plant salicylate metabolism pathway by suppressing its precursor. Furthermore, these proteins lack signal peptides, but exhibit characteristics that lead to unconventional secretion. Therefore, this secretion pathway is a novel mechanism for delivering effectors and might play an important role in host-pathogen interactions. PMID:25156390

  20. Unconventionally secreted effectors of two filamentous pathogens target plant salicylate biosynthesis

    PubMed Central

    Liu, Tingli; Song, Tianqiao; Zhang, Xiong; Yuan, Hongbo; Su, Liming; Li, Wanlin; Xu, Jing; Liu, Shiheng; Chen, Linlin; Chen, Tianzi; Zhang, Meixiang; Gu, Lichuan; Zhang, Baolong; Dou, Daolong

    2014-01-01

    Plant diseases caused by fungi and oomycetes pose an increasing threat to food security and ecosystem health worldwide. These filamentous pathogens, while taxonomically distinct, modulate host defense responses by secreting effectors, which are typically identified based on the presence of signal peptides. Here we show that Phytophthora sojae and Verticillium dahliae secrete isochorismatases (PsIsc1 and VdIsc1, respectively) that are required for full pathogenesis. PsIsc1 and VdIsc1 can suppress salicylate-mediated innate immunity in planta and hydrolyse isochorismate in vitro. A conserved triad of catalytic residues is essential for both functions. Thus, the two proteins are isochorismatase effectors that disrupt the plant salicylate metabolism pathway by suppressing its precursor. Furthermore, these proteins lack signal peptides, but exhibit characteristics that lead to unconventional secretion. Therefore, this secretion pathway is a novel mechanism for delivering effectors and might play an important role in host–pathogen interactions. PMID:25156390

  1. The Wnt signaling pathway is involved in the regulation of phagocytosis of virus in Drosophila.

    PubMed

    Zhu, Fei; Zhang, Xiaobo

    2013-01-01

    Phagocytosis is crucial for triggering host defenses against invading pathogens in animals. However, the receptors on phagocyte surface required for phagocytosis of virus have not been extensively explored. This study demonstrated that white spot syndrome virus (WSSV), a major pathogen of shrimp, could be engulfed but not digested by Drosophila S2 cells, indicating that the virus was not recognized and taken up by a pathway that was silent and would not activate the phagosome maturation and digestion pathway. The results showed that the activation of receptors on S2 cell surface by lipopolysaccharide or peptidoglycan resulted in the phagocytosis of S2 cells against WSSV virions. Gene expression profiles revealed that the dally-mediated Wnt signaling pathway was involved in S2 phagocytosis. Further data showed that the Wnt signaling pathway played an essential role in phagocytosis. Therefore, our study contributed novel insight into the molecular mechanism of phagocytosis in animals. PMID:23797713

  2. Activation of the Jasmonic Acid Plant Defence Pathway Alters the Composition of Rhizosphere Bacterial Communities

    PubMed Central

    Carvalhais, Lilia C.; Dennis, Paul G.; Badri, Dayakar V.; Tyson, Gene W.; Vivanco, Jorge M.; Schenk, Peer M.

    2013-01-01

    Jasmonic acid (JA) signalling plays a central role in plant defences against necrotrophic pathogens and herbivorous insects, which afflict both roots and shoots. This pathway is also activated following the interaction with beneficial microbes that may lead to induced systemic resistance. Activation of the JA signalling pathway via application of methyl jasmonate (MeJA) alters the composition of carbon containing compounds released by roots, which are implicated as key determinants of rhizosphere microbial community structure. In this study, we investigated the influence of the JA defence signalling pathway activation in Arabidopsis thaliana on the structure of associated rhizosphere bacterial communities using 16S rRNA gene amplicon pyrosequencing. Application of MeJA did not directly influence bulk soil microbial communities but significant changes in rhizosphere community composition were observed upon activation of the jasmonate signalling pathway. Our results suggest that JA signalling may mediate plant-bacteria interactions in the soil upon necrotrophic pathogen and herbivorous insect attacks. PMID:23424661

  3. Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis

    PubMed Central

    Young, George R; Stoye, Jonathan P; Kassiotis, George

    2013-01-01

    A number of observations have led researchers to postulate that, despite being replication-defective, human endogenous retroviruses (HERVs) may have retained the potential to cause or contribute to disease. However, mechanisms of HERV pathogenicity might differ substantially from those of modern infectious retroviruses or of the infectious precursors of HERVs. Therefore, novel pathways of HERV involvement in disease pathogenesis should be investigated. Recent technological advances in sequencing and bioinformatics are making this task increasingly feasible. The accumulating knowledge of HERV biology may also facilitate the definition and general acceptance of criteria that establish HERV pathogenicity. Here, we explore possible mechanisms whereby HERVs may cause disease and examine the evidence that either has been or should be obtained in order to decisively address the pathogenic potential of HERVs. PMID:23864388

  4. An Extracellular Bacterial Pathogen Modulates Host Metabolism to Regulate its Own Sensing and Proliferation

    PubMed Central

    Baruch, Moshe; Belotserkovsky, Ilia; Hertzog, Baruch B.; Ravins, Miriam; Dov, Eran; McIver, Kevin S.; Le Breton, Yoann S.; Zhou, Yiting; Youting, Catherine Cheng; Hanski, Emanuel

    2014-01-01

    SUMMARY Successful infection depends on the ability of the pathogen to gain nutrients from the host. The extracellular pathogenic bacterium group A Streptococcus (GAS) causes a vast array of human diseases. By using the quorum sensing sil system as a reporter, we found that during adherence to host cells GAS delivers streptolysin toxins creating endoplasmic reticulum stress. This in turn, increases asparagine (ASN) synthetase expression and the production of ASN. The released ASN is sensed by the bacteria altering the expression of ~17% of GAS genes of which about 1/3 are dependent on the two-component system TrxSR. The expression of the streptolysin toxins is strongly upregulated whereas genes linked to proliferation are downregulated in ASN absence. Asparaginase a widely used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS proliferation in a mouse model of human bacteremia. These results delineate a pathogenic pathway and propose a new therapeutic strategy against GAS infections. PMID:24439371

  5. Ras-Mediated Signal Transduction and Virulence in Human Pathogenic Fungi

    PubMed Central

    Fortwendel, Jarrod R.

    2013-01-01

    Signal transduction pathways regulating growth and stress responses are areas of significant study in the effort to delineate pathogenic mechanisms of fungi. In-depth knowledge of signal transduction events deepens our understanding of how a fungal pathogen is able to sense changes in the environment and respond accordingly by modulation of gene expression and re-organization of cellular activities to optimize fitness. Members of the Ras protein family are important regulators of growth and differentiation in eukaryotic organisms, and have been the focus of numerous studies exploring fungal pathogenesis. Here, the current data regarding Ras signal transduction are reviewed for three major pathogenic fungi: Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. Particular emphasis is placed on Ras-protein interactions during control of morphogenesis, stress response and virulence. PMID:24855584

  6. Updating the Wnt pathways.

    PubMed

    Yu, Jia; Virshup, David M

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  7. Updating the Wnt pathways

    PubMed Central

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  8. Original article Double staining (CTC-DAPI) for detection and

    E-print Network

    Paris-Sud XI, Université de

    Original article Double staining (CTC-DAPI) for detection and enumeration of viable but non cultivable INTRODUCTION A viable but non-culturable (VNC) bacte- rial state was originally detected of human pathogens: Escherichia coli (Xu et al, 1982), Salmonella enteritidi.s (Roszak et al, 1984), Vibrio

  9. RESEARCH ARTICLE Open Access Comparative analysis of Klebsiella pneumoniae

    E-print Network

    Paris-Sud XI, Université de

    RESEARCH ARTICLE Open Access Comparative analysis of Klebsiella pneumoniae genomes identifies Background: Klebsiella pneumoniae strains are pathogenic to animals and humans, in which they are both, Lipid metabolism Background Klebsiella pneumoniae is responsible for a variety of dis- eases in humans

  10. Research Article Spread of Plague Among Black-Tailed Prairie

    E-print Network

    Collinge, Sharon K.

    Research Article Spread of Plague Among Black-Tailed Prairie Dogs Is Associated With Colony Spatial Sylvatic plague (Yersinia pestis) is an exotic pathogen that is highly virulent in black-tailed prairie investigated colony spatial characteristics that may influence inter-colony transmission of plague at 3 prairie

  11. Original article Sortase anchored proteins of Streptococcus uberis

    E-print Network

    Boyer, Edmond

    Original article Sortase anchored proteins of Streptococcus uberis play major roles March 2010; accepted 2 June 2010) Abstract ­ Streptococcus uberis, strain 0140J, contains a single copy / sortase / vaccine 1. INTRODUCTION Streptococcus uberis is one of the most com- mon pathogens isolated from

  12. Review article Secretion of virulence factors by Escherichia coli

    E-print Network

    Paris-Sud XI, Université de

    Review article Secretion of virulence factors by Escherichia coli Bernard China* Fréderic Goffaux with their host, pathogenic strains of E. coli need to secrete some virulence factors which can modify the metabolism of host cells, contributing to disease. Since E. coli is a Gram-negative bacteria, this secretion

  13. Probing Pathways Periodically

    NSDL National Science Digital Library

    Timothy C. Elston (Chapel Hill; University of North Carolina REV)

    2008-10-21

    Signal transduction pathways are used by cells to process and transmit information about their external surroundings. These systems are dynamic, interconnected molecular networks. Therefore, full characterization of their behavior requires a systems-level analysis. Investigations with temporally oscillating input signals probed the dynamic properties of the high-osmolarity glycerol (HOG) pathway of the budding yeast Saccharomyces cerevisiae. These studies shed light on how the network functions as a whole to respond to changing environmental conditions.

  14. TLR signaling pathways

    Microsoft Academic Search

    Kiyoshi Takeda; Shizuo Akira

    2004-01-01

    Toll-like receptors (TLRs) have been established to play an essential role in the activation of innate immunity by recognizing specific patterns of microbial components. TLR signaling pathways arise from intracytoplasmic TIR domains, which are conserved among all TLRs. Recent accumulating evidence has demonstrated that TIR domain-containing adaptors, such as MyD88, TIRAP, and TRIF, modulate TLR signaling pathways. MyD88 is essential

  15. Mitogen Activated Protein kinase signal transduction pathways in the prostate

    Microsoft Academic Search

    Paul D Maroni; Sweaty Koul; Randall B Meacham; Hari K Koul

    2004-01-01

    The biochemistry of the mitogen activated protein kinases ERK, JNK, and p38 have been studied in prostate physiology in an attempt to elucidate novel mechanisms and pathways for the treatment of prostatic disease. We reviewed articles examining mitogen-activated protein kinases using prostate tissue or cell lines. As with other tissue types, these signaling modules are links\\/transmitters for important pathways in

  16. Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack.

    PubMed

    De Vos, Martin; Van Oosten, Vivian R; Van Poecke, Remco M P; Van Pelt, Johan A; Pozo, Maria J; Mueller, Martin J; Buchala, Antony J; Métraux, Jean-Pierre; Van Loon, L C; Dicke, Marcel; Pieterse, Corné M J

    2005-09-01

    Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and E occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response. PMID:16167763

  17. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens

    PubMed Central

    Ng, Katharine M.; Ferreyra, Jessica A.; Higginbottom, Steven K.; Lynch, Jonathan B.; Kashyap, Purna C.; Gopinath, Smita; Naidu, Natasha; Choudhury, Biswa; Weimer, Bart C.; Monack, Denise M.; Sonnenburg, Justin L.

    2013-01-01

    The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens1–4. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella typhimurium and Clostridium difficile, employ a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of the model gut symbiont Bacteroides thetaiotaomicron (Bt) reduces free sialic acid levels resulting in a downregulation of C. difficile’s sialic acid catabolic pathway and impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new possibilities for therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens. PMID:23995682

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

    PubMed

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

    2015-03-01

    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 and intracellular spread. PMID:25738731

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

    PubMed Central

    Memiševi?, 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 and intracellular spread. PMID:25738731

  20. Insights into Acinetobacter baumannii pathogenicity.

    PubMed

    Cerqueira, Gustavo M; Peleg, Anton Y

    2011-12-01

    Acinetobacter spp. have justifiably received significant attention from the public, scientific, and medical communities. Over recent years, Acinetobacter, particularly Acinetobacter baumannii, has become a "red-alert" human pathogen, primarily because of its exceptional ability to develop resistance to all currently available antibiotics. This characteristic is compounded by its unique abilities to survive in a diverse range of environments, including those within healthcare institutions, leading to problematic outbreaks. Historically, the virulence of the organism has been questioned, but recent clinical reports suggest that Acinetobacter can cause serious, life-threatening infections. Furthermore, its metabolic adaptability gives it a selective advantage in harsh hospital environments. This review focuses on current understanding of A. baumannii pathogenesis and the model systems used to study this interesting organism. PMID:21989983

  1. National Microbial Pathogen Data Resource

    NSDL National Science Digital Library

    NMPDR

    Overview on searching, navigating, and teaching with NMPDR. Presentations on connecting bioinformatics to the bench, and subsystems annotation. Assignments exploring biosynthesis and pathogenesis. Documents on using GBrowse, and SEED. ***Notice to NMPDR Users*** The NMPDR BRC contract ended in December 2009. At that time we ceased maintenance of the NMPDR web resource and data. The PATRIC team, located at the Virginia Bioinformatics Institute, created and maintains a new consolidated BRC for all of the NIAID category A-C priority pathogenic bacteria. NMPDR is transferring data and software associated to PATRIC for incorporation into their new Web-based bioinformatics resource. Please feel free to contact us if you have any questions about this transition.

  2. A Nod to disease vectors: mitigation of pathogen sensing by arthropod saliva

    PubMed Central

    Sakhon, Olivia S.; Severo, Maiara S.; Kotsyfakis, Michail; Pedra, Joao H. F.

    2013-01-01

    Arthropod saliva possesses anti-hemostatic, anesthetic, and anti-inflammatory properties that facilitate feeding and, inadvertently, dissemination of pathogens. Vector-borne diseases caused by these pathogens affect millions of people each year. Many studies address the impact of arthropod salivary proteins on various immunological components. However, whether and how arthropod saliva counters Nod-like (NLR) sensing remains elusive. NLRs are innate immune pattern recognition molecules involved in detecting microbial molecules and danger signals. Nod1/2 signaling results in activation of the nuclear factor-?B and the mitogen-activated protein kinase pathways. Caspase-1 NLRs regulate the inflammasome~– a protein scaffold that governs the maturation of interleukin (IL)-1? and IL-18. Recently, several vector-borne pathogens have been shown to induce NLR activation in immune cells. Here, we provide a brief overview of NLR signaling and discuss clinically relevant vector-borne pathogens recognized by NLR pathways. We also elaborate on possible anti-inflammatory effects of arthropod saliva on NLR signaling and microbial pathogenesis for the purpose of exchanging research perspectives. PMID:24155744

  3. Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism.

    PubMed

    Gonzalo, Hugo; Brieva, Luis; Tatzber, Franz; Jové, Mariona; Cacabelos, Daniel; Cassanyé, Anna; Lanau-Angulo, Lucia; Boada, Jordi; Serrano, José C E; González, Cristina; Hernández, Lourdes; Peralta, Sílvia; Pamplona, Reinald; Portero-Otin, Manuel

    2012-11-01

    Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2? is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor ? (PPAR?). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS. PMID:22924648

  4. Regulation of primary plant metabolism during plant-pathogen interactions and its contribution to plant defense

    PubMed Central

    Rojas, Clemencia M.; Senthil-Kumar, Muthappa; Tzin, Vered; Mysore, Kirankumar S.

    2014-01-01

    Plants are constantly exposed to microorganisms in the environment and, as a result, have evolved intricate mechanisms to recognize and defend themselves against potential pathogens. One of these responses is the downregulation of photosynthesis and other processes associated with primary metabolism that are essential for plant growth. It has been suggested that the energy saved by downregulation of primary metabolism is diverted and used for defense responses. However, several studies have shown that upregulation of primary metabolism also occurs during plant-pathogen interactions. We propose that upregulation of primary metabolism modulates signal transduction cascades that lead to plant defense responses. In support of this thought, we here compile evidence from the literature to show that upon exposure to pathogens or elicitors, plants induce several genes associated with primary metabolic pathways, such as those involved in the synthesis or degradation of carbohydrates, amino acids and lipids. In addition, genetic studies have confirmed the involvement of these metabolic pathways in plant defense responses. This review provides a new perspective highlighting the relevance of primary metabolism in regulating plant defense against pathogens with the hope to stimulate further research in this area. PMID:24575102

  5. Pathogenic Roles for Fungal Melanins

    PubMed Central

    Jacobson, Eric S.

    2000-01-01

    Melanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H2O2. Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning. PMID:11023965

  6. Application of complementation tests in identifying pathogenicity determinants of the chickpea pathogen Ascochyta rabiei

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The necrotrophic pathogen Ascochyta rabiei causes chickpea Ascochyta blight. Very little is known about its pathogenicity mechanisms. The objective of this research was to identify pathogenicity determinants of A. rabiei using complementation tests. The hygromycin-resistant mutant ArW519 was non-pa...

  7. Biological Pathways A pathway to explore diseases mechanism

    E-print Network

    1 Biological Pathways ­ A pathway to explore diseases mechanism Ming Guo Abstract Diseases are increasingly identified with genetic modules, such as molecular pathways. Pathway role in understanding diseases mechanism from genetic studies. This paper is a review of the various

  8. Effective but Costly, Evolved Mechanisms of Defense against a Virulent Opportunistic Pathogen in Drosophila melanogaster

    PubMed Central

    Ye, Yixin H.; Chenoweth, Stephen F.; McGraw, Elizabeth A.

    2009-01-01

    Drosophila harbor substantial genetic variation for antibacterial defense, and investment in immunity is thought to involve a costly trade-off with life history traits, including development, life span, and reproduction. To understand the way in which insects invest in fighting bacterial infection, we selected for survival following systemic infection with the opportunistic pathogen Pseudomonas aeruginosa in wild-caught Drosophila melanogaster over 10 generations. We then examined genome-wide changes in expression in the selected flies relative to unselected controls, both of which had been infected with the pathogen. This powerful combination of techniques allowed us to specifically identify the genetic basis of the evolved immune response. In response to selection, population-level survivorship to infection increased from 15% to 70%. The evolved capacity for defense was costly, however, as evidenced by reduced longevity and larval viability and a rapid loss of the trait once selection pressure was removed. Counter to expectation, we observed more rapid developmental rates in the selected flies. Selection-associated changes in expression of genes with dual involvement in developmental and immune pathways suggest pleiotropy as a possible mechanism for the positive correlation. We also found that both the Toll and the Imd pathways work synergistically to limit infectivity and that cellular immunity plays a more critical role in overcoming P. aeruginosa infection than previously reported. This work reveals novel pathways by which Drosophila can survive infection with a virulent pathogen that may be rare in wild populations, however, due to their cost. PMID:19381251

  9. Publishing International Counseling Articles

    ERIC Educational Resources Information Center

    Hohenshil, Thomas H.; Amundson, Norman E.

    2011-01-01

    This article begins with a rationale for including international articles in the "Journal of Counseling & Development." Then, 2 general categories of international articles are described. First are articles that provide a general overview of counseling in a particular country. The 2nd category is more general and might involve international…

  10. The care pathway: concepts and theories: an introduction.

    PubMed

    Schrijvers, Guus; van Hoorn, Arjan; Huiskes, Nicolette

    2012-01-01

    This article addresses first the definition of a (care) pathway, and then follows a description of theories since the 1950s. It ends with a discussion of theoretical advantages and disadvantages of care pathways for patients and professionals. The objective of this paper is to provide a theoretical base for empirical studies on care pathways. The knowledge for this chapter is based on several books on pathways, which we found by searching in the digital encyclopedia Wikipedia. Although this is not usual in scientific publications, this method was used because books are not searchable by databases as Pubmed. From 2005, we performed a literature search on Pubmed and other literature databases, and with the keywords integrated care pathway, clinical pathway, critical pathway, theory, research, and evaluation. One of the inspirational sources was the website of the European Pathway Association (EPA) and its journal International Journal of Care Pathways. The authors visited several sites for this paper. These are mentioned as illustration of a concept or theory. Most of them have English websites with more information. The URLs of these websites are not mentioned in this paper as a reference, because the content of them changes fast, sometimes every day. PMID:23593066

  11. The care pathway: concepts and theories: an introduction

    PubMed Central

    Schrijvers, Guus; van Hoorn, Arjan; Huiskes, Nicolette

    2012-01-01

    This article addresses first the definition of a (care) pathway, and then follows a description of theories since the 1950s. It ends with a discussion of theoretical advantages and disadvantages of care pathways for patients and professionals. The objective of this paper is to provide a theoretical base for empirical studies on care pathways. The knowledge for this chapter is based on several books on pathways, which we found by searching in the digital encyclopedia Wikipedia. Although this is not usual in scientific publications, this method was used because books are not searchable by databases as Pubmed. From 2005, we performed a literature search on Pubmed and other literature databases, and with the keywords integrated care pathway, clinical pathway, critical pathway, theory, research, and evaluation. One of the inspirational sources was the website of the European Pathway Association (EPA) and its journal International Journal of Care Pathways. The authors visited several sites for this paper. These are mentioned as illustration of a concept or theory. Most of them have English websites with more information. The URLs of these websites are not mentioned in this paper as a reference, because the content of them changes fast, sometimes every day. PMID:23593066

  12. The phosphoinositide 3-kinase pathway and therapy resistance in cancer

    PubMed Central

    2015-01-01

    The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling network is a master regulator of processes that contribute to tumorigenesis and tumor maintenance. The PI3K pathway also plays a critical role in driving resistance to diverse anti-cancer therapies. This review article focuses on mechanisms by which the PI3K pathway contributes to therapy resistance in cancer, and highlights potential combination therapy strategies to circumvent resistance driven by PI3K signaling. In addition, resistance mechanisms that limit the clinical efficacy of small molecule inhibitors of the PI3K pathway are discussed. PMID:25750731

  13. 76 FR 24793 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ...APHIS-2006-0074] RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant Health...where any subtype of highly pathogenic avian influenza is considered to exist. The...have been vaccinated for certain types of avian influenza, or that have moved...

  14. Pathogen threat assessment is predictive plant pathology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The American Society of Plant Pathologists has maintained a formal effort to prioritize threatening and emerging crop pathogens for over 70 years, and the APS Emerging Pathogens and Diseases Committee is continuing the process. In order to accomplish prioritization in a rigorous fashion, criteria mu...

  15. Plant pathology Characterization and pathogenicity on seedlings

    E-print Network

    Paris-Sud XI, Université de

    Plant pathology Characterization and pathogenicity on seedlings of Pythium species isolated from plants growing near Toulouse (SW France). Approximately half of all isolates were pathogenic on soybean root growth and caused no visible symptoms. P ultimum was only isolated from young plants; P irregulare

  16. Hunting for insect pathogens: A genomics approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Emerging methods within the field of genomics have increased the number of insect pathogens being discovered and characterized each year. These pathogens provide a rich resource for biological control agents, gene expression systems, and other molecular tools. Using Metagenomics, and gene expression...

  17. SUGAR METABOLISM AND PATHOGENICITY OF SPIROPLASMA CITRI

    Microsoft Academic Search

    J. Renaudin

    2006-01-01

    SUMMARY Spiroplasma citri is a plant-pathogenic mollicute, phy- logenetically related to Gram-positive bacteria. Spiro- plasma cells are restricted to the phloem sieve elements and are transmitted by leafhopper vectors. Recent re- search has allowed depicting a unique scenario in S. citri pathogenicity, where sugar metabolism plays a major role. In vitro S. citri uses fructose, glucose, and trehalose, which are

  18. New and Emerging Pathogens of Blueberry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-lived woody perennial crops, such as blueberry, are continually exposed to a host of pathogens. The ‘success’ or importance of these pathogens is dependent on a combination of important factors including cultivar susceptibility, environmental conditions, cultural practices, and inoculum pressur...

  19. Microsatellite markers in plant pathogenic fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowing the genetic diversity of plant pathogenic fungi is essential in the management of crops and disease. The genetic variability of fungal pathogens can be evaluated using molecular markers, among which, microsatellites are a relatively inexpensive source of information. We have developed an e...

  20. PATHOGENICITY OF AVIAN INFLUENZA VIRUSES IN POULTRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historically, the pathogenicity of avian influenza (AI) viruses has been based on lethality for the major domesticated poultry species, the chicken. All AI viruses are categorized as either low (LP) and high pathogenicity (HP), but within each category, pathobiological changes vary with host species...

  1. Resistance to Bacterial Pathogens in Plants

    E-print Network

    Innes, Roger

    ). Disease symptoms caused by bacterial pathogens include wilts, galls, specks, spots, cankers and chlorosis in causing soft-rot diseases in- duced by bacteria in the Erwinia genus. Basal Defence against BacterialResistance to Bacterial Pathogens in Plants Jules Ade, Indiana University, Bloomington, Indiana

  2. Arthropods vector grapevine trunk disease pathogens.

    PubMed

    Moyo, P; Allsopp, E; Roets, F; Mostert, L; Halleen, F

    2014-10-01

    ABSTRACT Arthropod-mediated dispersal of pathogens is known in many cropping systems but has never been demonstrated for grapevine trunk disease pathogens. Arthropods from vineyards were screened for the presence of pathogens associated with Petri disease and esca using cultural and molecular techniques. The ability of the most abundant pathogen-carrying species to inoculate healthy grapevine vascular tissues was also determined. Millipedes and ants were allowed to associate with a DsRed- Express-transformed Phaeomoniella chlamydospora, after which they were exposed to freshly pruned healthy grapevines under controlled conditions and wounds were monitored for subsequent infection. In addition, the possibility of millipede excreta, commonly found on pruning wounds in the field, to act as inoculum source was determined. A diverse arthropod fauna was associated with declining grapevines and many of these carried trunk disease pathogens. However, spiders, the ant Crematogaster peringueyi, and the millipede Ommattoiulus moreleti were the most abundant pathogen carriers. The ant and millipede species fed on pruning wound sap and effectively transmitted trunk disease pathogens. Millipede excreta contained viable spores of Phaeomoniella chlamydospora and may serve as an inoculum source. Numerous arthropods, including beneficial predators, are potential vectors of grapevine trunk disease pathogens. Our results highlight the need for an integrated approach, including targeted management of ants and millipedes at the time of pruning, to limit the spread of grapevine trunk diseases. PMID:24624953

  3. TREATMENT OF MUNICIPAL SLUDGE FOR PATHOGEN REDUCTION

    EPA Science Inventory

    This presentation reviews the pathogenic microorganisms that may be found in municipal sewage sludge and the commonly employed Class A and B processes for controlling pathogens. It notes how extensively they are used and discusses issues and concerns with their application. The...

  4. Insect pathogens: molecular approaches and techniques

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book serves as a primer for molecular techniques in insect pathology and is tailored for a wide scientific audience. Contributing authors are internationally recognized experts. The book comprises four sections: 1) pathogen identification and diagnostics, 2) pathogen population genetics and p...

  5. Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

    PubMed Central

    Nan, Yuchen; Nan, Guoxin; Zhang, Yan-Jin

    2014-01-01

    Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR). Host PRR for RNA viruses include Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses. PMID:25514371

  6. Evolutionary implications of hostpathogen specificity: fitness consequences of pathogen

    E-print Network

    Kirchner, James W.

    Evolutionary implications of host­pathogen specificity: fitness consequences of pathogen virulence (ETH), Zürichbergstrasse 38, CH-8044 Zürich, Switzerland ABSTRACT Pathogens and parasites can be strong a simple host­pathogen model to explore the con- sequences of host­pathogen specificity for selection

  7. Ras Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans

    PubMed Central

    Inglis, Diane O.

    2013-01-01

    Candida albicans is an opportunistic fungal pathogen that can cause disseminated infection in patients with indwelling catheters or other implanted medical devices. A common resident of the human microbiome, C. albicans responds to environmental signals, such as cell contact with catheter materials and exposure to serum or CO2, by triggering the expression of a variety of traits, some of which are known to contribute to its pathogenic lifestyle. Such traits include adhesion, biofilm formation, filamentation, white-to-opaque (W-O) switching, and two recently described phenotypes, finger and tentacle formation. Under distinct sets of environmental conditions and in specific cell types (mating type-like a [MTLa]/alpha cells, MTL homozygotes, or daughter cells), C. albicans utilizes (or reutilizes) a single signal transduction pathway—the Ras pathway—to affect these phenotypes. Ras1, Cyr1, Tpk2, and Pde2, the proteins of the Ras signaling pathway, are the only nontranscriptional regulatory proteins that are known to be essential for regulating all of these processes. How does C. albicans utilize this one pathway to regulate all of these phenotypes? The regulation of distinct and yet related processes by a single, evolutionarily conserved pathway is accomplished through the use of downstream transcription factors that are active under specific environmental conditions and in different cell types. In this minireview, we discuss the role of Ras signaling pathway components and Ras pathway-regulated transcription factors as well as the transcriptional regulatory networks that fine-tune gene expression in diverse biological contexts to generate specific phenotypes that impact the virulence of C. albicans. PMID:23913542

  8. Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum

    SciTech Connect

    Wiedner, Susan D.; Burnum, Kristin E.; Pederson, Leeanna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigne-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

    2012-08-03

    Environmental and metabolic adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised lung. We employed an activity-based protein profiling (ABPP) approach utilizing a new aryl vinyl sulfonate probe and a serine hydrolase probe combined with quantitative LC-MS based accurate mass and time (AMT) tag proteomics for the identification of functional pathway adaptation of A. fumigatus to environmental variability relevant to pulmonary Invasive Aspergillosis. When the fungal pathogen was grown with human serum, metabolism and energy processes were markedly decreased compared to no serum culture. Additionally, functional pathways associated with amino acid and protein biosynthesis were limited as the fungus scavenged from the serum to obtain essential nutrients. Our approach revealed significant metabolic adaptation by A. fumigatus, and provides direct insight into this pathogen’s ability to survive and proliferate.

  9. Phytophthora parasitica: a model oomycete plant pathogen

    PubMed Central

    Meng, Yuling; Zhang, Qiang; Ding, Wei; Shan, Weixing

    2014-01-01

    Oomycetes are eukaryotic microorganisms morphologically similar to but phylogenetically distant from true fungi. Most species in the genus Phytophthora of oomycetes are devastating plant pathogens, causing damages to both agricultural production and natural ecosystems. Tremendous progress has been achieved in recent years in diversity, evolution and lifestyles of oomycete plant pathogens, as well as on the understanding of genetic and molecular basis of oomycete-plant interactions. Phytophthora parasitica is a soilborne pathogen with a wide range of host plants and represents most species in the genus Phytophthora. In this review, we present some recent progress of P. parasitica research by highlighting important features that make it emerge as a model species of oomycete pathogens. The emerged model pathogen will facilitate improved understanding of oomycete biology and pathology that are crucial to the development of novel disease-control strategies and improved disease-control measures. PMID:24999436

  10. Host Range and Emerging and Reemerging Pathogens

    PubMed Central

    Gowtage-Sequeria, Sonya

    2005-01-01

    An updated literature survey identified 1,407 recognized species of human pathogen, 58% of which are zoonotic. Of the total, 177 are regarded as emerging or reemerging. Zoonotic pathogens are twice as likely to be in this category as are nonzoonotic pathogens. Emerging and reemerging pathogens are not strongly associated with particular types of nonhuman hosts, but they are most likely to have the broadest host ranges. Emerging and reemerging zoonoses are associated with a wide range of drivers, but changes in land use and agriculture and demographic and societal changes are most commonly cited. However, although zoonotic pathogens do represent the most likely source of emerging and reemerging infectious disease, only a small minority have proved capable of causing major epidemics in the human population. PMID:16485468

  11. IgG1 Is Pathogenic in Leishmania mexicana Infection

    PubMed Central

    Chu, Niansheng; Thomas, Bolaji N.; Patel, Supriya R.; Buxbaum, Laurence U.

    2010-01-01

    There are over 2 million new cases of leishmaniasis annually, and no effective vaccine has been developed to prevent infection. In murine infection, Leishmania mexicana, which lives intracellularly in host macrophages, has developed pathways to hijack host IgG to induce a suppressive IL-10 response through Fc?Rs, the cell-surface receptors for IgG. To guide vaccine development away from detrimental Ab responses, which can accompany attempts to induce cell-mediated immunity, it is crucial to know which isotypes of IgG are pathogenic in this infection. We have found that IgG1 and IgG2a/c induce IL-10 from macrophages in vitro equally well but through different Fc?R subtypes: IgG1 through Fc?RIII, and IgG2a/c through Fc?RI primarily, but also through Fc?RIII. In sharp contrast, mice lacking IgG1 develop earlier and stronger IgG2a/c, IgG3, and IgM responses to L. mexicana infection and yet are more resistant to the infection. Thus, IgG1, but not IgG2a/c or IgG3, is pathogenic in vivo, in agreement with prior studies indicating that Fc?RIII is required for chronic disease. This calls into question the assumption that macrophages, which should secrete IL-10 in response to both IgG1 and IgG2a/c immune complexes, are the most important source of IL-10 generated by IgG-Fc?R engagement in L. mexicana infection. Further investigations are required to better determine the cell type responsible for this immunosuppressive Fc?RIII-induced IL-10 pathway and whether IgG2a/c is protective. PMID:21037092

  12. Algae as Reservoirs for Coral Pathogens

    PubMed Central

    Sweet, Michael J.; Bythell, John C.; Nugues, Maggy M.

    2013-01-01

    Benthic algae are associated with coral death in the form of stress and disease. It's been proposed that they release exudates, which facilitate invasion of potentially pathogenic microbes at the coral-algal interface, resulting in coral disease. However, the original source of these pathogens remains unknown. This study examined the ability of benthic algae to act as reservoirs of coral pathogens by characterizing surface associated microbes associated with major Caribbean and Indo-Pacific algal species/types and by comparing them to potential pathogens of two dominant coral diseases: White Syndrome (WS) in the Indo-Pacific and Yellow Band Disease (YBD) in the Caribbean. Coral and algal sampling was conducted simultaneously at the same sites to avoid spatial effects. Potential pathogens were defined as those absent or rare in healthy corals, increasing in abundance in healthy tissues adjacent to a disease lesion, and dominant in disease lesions. Potentially pathogenic bacteria were detected in both WS and YBD and were also present within the majority of algal species/types (54 and 100% for WS and YBD respectively). Pathogenic ciliates were associated only with WS and not YBD lesions and these were also present in 36% of the Indo-Pacific algal species. Although potential pathogens were associated with many algal species, their presence was inconsistent among replicate algal samples and detection rates were relatively low, suggestive of low density and occurrence. At the community level, coral-associated microbes irrespective of the health of their host differed from algal-associated microbes, supporting that algae and corals have distinctive microbial communities associated with their tissue. We conclude that benthic algae are common reservoirs for a variety of different potential coral pathogens. However, algal-associated microbes alone are unlikely to cause coral death. Initial damage or stress to the coral via other competitive mechanisms is most likely a prerequisite to potential transmission of these pathogens. PMID:23936086

  13. Algae as reservoirs for coral pathogens.

    PubMed

    Sweet, Michael J; Bythell, John C; Nugues, Maggy M

    2013-01-01

    Benthic algae are associated with coral death in the form of stress and disease. It's been proposed that they release exudates, which facilitate invasion of potentially pathogenic microbes at the coral-algal interface, resulting in coral disease. However, the original source of these pathogens remains unknown. This study examined the ability of benthic algae to act as reservoirs of coral pathogens by characterizing surface associated microbes associated with major Caribbean and Indo-Pacific algal species/types and by comparing them to potential pathogens of two dominant coral diseases: White Syndrome (WS) in the Indo-Pacific and Yellow Band Disease (YBD) in the Caribbean. Coral and algal sampling was conducted simultaneously at the same sites to avoid spatial effects. Potential pathogens were defined as those absent or rare in healthy corals, increasing in abundance in healthy tissues adjacent to a disease lesion, and dominant in disease lesions. Potentially pathogenic bacteria were detected in both WS and YBD and were also present within the majority of algal species/types (54 and 100% for WS and YBD respectively). Pathogenic ciliates were associated only with WS and not YBD lesions and these were also present in 36% of the Indo-Pacific algal species. Although potential pathogens were associated with many algal species, their presence was inconsistent among replicate algal samples and detection rates were relatively low, suggestive of low density and occurrence. At the community level, coral-associated microbes irrespective of the health of their host differed from algal-associated microbes, supporting that algae and corals have distinctive microbial communities associated with their tissue. We conclude that benthic algae are common reservoirs for a variety of different potential coral pathogens. However, algal-associated microbes alone are unlikely to cause coral death. Initial damage or stress to the coral via other competitive mechanisms is most likely a prerequisite to potential transmission of these pathogens. PMID:23936086

  14. Terrific Protein Traffic: The Mystery of Effector Protein Delivery by Filamentous Plant Pathogens

    NSDL National Science Digital Library

    Ralph Panstruga (Max-Planck Institute for Plant Breeding Research; Department of Plant-Microbe Interactions)

    2009-05-08

    Access to the article is free, however registration and sign-in are required. Many biotrophic fungal and oomycete plant pathogens deliver effector proteins directly into host cells during infection. Recent advances are revealing the extensive effector repertoires of these pathogens and are beginning to shed light on how they manipulate host cells to establish a parasitic relationship. The current explosion of information is opening new research avenues in molecular plant pathology and is providing new opportunities to limit the impact of plant disease on food production.

  15. Subtilisin-like proteases in plant–pathogen recognition and immune priming: a perspective

    PubMed Central

    Figueiredo, Andreia; Monteiro, Filipa; Sebastiana, Mónica

    2014-01-01

    Subtilisin-like proteases (subtilases) are serine proteases that fulfill highly specific functions in plant development and signaling cascades. Over the last decades, it has been shown that several subtilases are specifically induced following pathogen infection and very recently an Arabidopsis subtilase (SBT3.3) was hypothesized to function as a receptor located in the plasma membrane activating downstream immune signaling processes. Despite their prevalence and potential relevance in the regulation of plant defense mechanisms and crop improvement, our current understanding of subtilase function is still very limited. In this perspective article, we overview the current status and highlight the involvement of subtilases in pathogen recognition and immune priming. PMID:25566306

  16. Pathogenic psychrotolerant sporeformers: an emerging challenge for low-temperature storage of minimally processed foods.

    PubMed

    Markland, Sarah M; Farkas, Daniel F; Kniel, Kalmia E; Hoover, Dallas G

    2013-05-01

    Sporeforming bacteria are a significant problem in the food industry as they are ubiquitous in nature and capable of resisting inactivation by heat and chemical treatments designed to inactivate them. Beyond spoilage issues, psychrotolerant sporeformers are becoming increasingly recognized as a potential hazard given the ever-expanding demand for refrigerated processed foods with extended shelf-life. In these products, the sporeforming pathogens of concern are Bacillus cereus, Bacillus weihenstephanensis, and Clostridium botulinum type E. This review article examines the foods, conditions, and organisms responsible for the food safety issue caused by the germination and outgrowth of psychrotolerant sporeforming pathogens in minimally processed refrigerated foods. PMID:23536982

  17. Quantitative Resistance of Potato to Pectobacterium atrosepticum and Phytophthora infestans: Integrating PAMP-Triggered Response and Pathogen Growth

    PubMed Central

    Kröner, Alexander; Hamelin, Gaëlle; Andrivon, Didier; Val, Florence

    2011-01-01

    While the mechanisms underlying quantitative resistance of plants to pathogens are still not fully elucidated, the Pathogen-Associated Molecular Patterns (PAMPs)-triggered response model suggests that such resistance depends on a dynamic interplay between the plant and the pathogen. In this model, the pathogens themselves or elicitors they produce would induce general defense pathways, which in turn limit pathogen growth and host colonisation. It therefore suggests that quantitative resistance is directly linked to a common set of general host defense mechanisms, but experimental evidence is still inconclusive. We tested the PAMP-triggered model using two pathogens (Pectobacterium atrosepticum and Phytophthora infestans) differing by their infectious processes and five potato cultivars spanning a range of resistance levels to each pathogen. Phenylalanine ammonia-lyase (PAL) activity, used as a defense marker, and accumulation of phenolics were measured in tuber slices challenged with lipopolysaccharides from P. atrosepticum or a concentrated culture filtrate from P. infestans. PAL activity increased following treatment with the filtrate but not with lipopolysaccharides, and varied among cultivars. It was positively related to tuber resistance to P. atrosepticum, but negatively related to tuber resistance to P. infestans. It was also positively related to the accumulation of total phenolics. Chlorogenic acid, the main phenolic accumulated, inhibited growth of both pathogens in vitro, showing that PAL induction caused active defense against each of them. Tuber slices in which PAL activity had been induced before inoculation showed increased resistance to P. atrosepticum, but not to P. infestans. Our results show that inducing a general defense mechanism does not necessarily result in quantitative resistance. As such, they invalidate the hypothesis that the PAMP-triggered model alone can explain quantitative resistance. We thus designed a more complex model integrating physiological host response and a key pathogen life history trait, pathogen growth, to explain the differences between the two pathosystems. PMID:21853112

  18. Signaling pathways in the development of infantile hemangioma

    PubMed Central

    2014-01-01

    Infantile hemangioma (IH), which is the most common tumor in infants, is a benign vascular neoplasm resulting from the abnormal proliferation of endothelial cells and pericytes. For nearly a century, researchers have noted that IH exhibits diverse and often dramatic clinical behaviors. On the one hand, most lesions pose no threat or potential for complication and resolve spontaneously without concern in most children with IH. On the other hand, approximately 10% of IHs are destructive, disfiguring and even vision- or life-threatening. Recent studies have provided some insight into the pathogenesis of these vascular tumors, leading to a better understanding of the biological features of IH and, in particular, indicating that during hemangioma neovascularization, two main pathogenic mechanisms prevail, angiogenesis and vasculogenesis. Both mechanisms have been linked to alterations in several important cellular signaling pathways. These pathways are of interest from a therapeutic perspective because targeting them may help to reverse, delay or prevent hemangioma neovascularization. In this review, we explore some of the major pathways implicated in IH, including the VEGF/VEGFR, Notch, ?-adrenergic, Tie2/angiopoietins, PI3K/AKT/mTOR, HIF-?-mediated and PDGF/PDGF-R-? pathways. We focus on the role of these pathways in the pathogenesis of IH, how they are altered and the consequences of these abnormalities. In addition, we review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against some of these pathways. PMID:24479731

  19. Signaling pathways in the development of infantile hemangioma.

    PubMed

    Ji, Yi; Chen, Siyuan; Li, Kai; Li, Li; Xu, Chang; Xiang, Bo

    2014-01-01

    Infantile hemangioma (IH), which is the most common tumor in infants, is a benign vascular neoplasm resulting from the abnormal proliferation of endothelial cells and pericytes. For nearly a century, researchers have noted that IH exhibits diverse and often dramatic clinical behaviors. On the one hand, most lesions pose no threat or potential for complication and resolve spontaneously without concern in most children with IH. On the other hand, approximately 10% of IHs are destructive, disfiguring and even vision- or life-threatening. Recent studies have provided some insight into the pathogenesis of these vascular tumors, leading to a better understanding of the biological features of IH and, in particular, indicating that during hemangioma neovascularization, two main pathogenic mechanisms prevail, angiogenesis and vasculogenesis. Both mechanisms have been linked to alterations in several important cellular signaling pathways. These pathways are of interest from a therapeutic perspective because targeting them may help to reverse, delay or prevent hemangioma neovascularization. In this review, we explore some of the major pathways implicated in IH, including the VEGF/VEGFR, Notch, ?-adrenergic, Tie2/angiopoietins, PI3K/AKT/mTOR, HIF-?-mediated and PDGF/PDGF-R-? pathways. We focus on the role of these pathways in the pathogenesis of IH, how they are altered and the consequences of these abnormalities. In addition, we review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against some of these pathways. PMID:24479731

  20. Pyruvate Protects Pathogenic Spirochetes from H2O2 Killing

    PubMed Central

    Troxell, Bryan; Zhang, Jun-Jie; Bourret, Travis J.; Zeng, Melody Yue; Blum, Janice; Gherardini, Frank; Hassan, Hosni M.; Yang, X. Frank

    2014-01-01

    Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (?0.6 µM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected ?uvrB and ?mutS from H2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi, which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H2O2 generated by the host antibacterial response generated during infection. PMID:24392147

  1. Experimental evolution of a plant pathogen into a legume symbiont.

    PubMed

    Marchetti, Marta; Capela, Delphine; Glew, Michelle; Cruveiller, Stéphane; Chane-Woon-Ming, Béatrice; Gris, Carine; Timmers, Ton; Poinsot, Véréna; Gilbert, Luz B; Heeb, Philipp; Médigue, Claudine; Batut, Jacques; Masson-Boivin, Catherine

    2010-01-01

    Rhizobia are phylogenetically disparate alpha- and beta-proteobacteria that have achieved the environmentally essential function of fixing atmospheric nitrogen in symbiosis with legumes. Ample evidence indicates that horizontal transfer of symbiotic plasmids/islands has played a crucial role in rhizobia evolution. However, adaptive mechanisms that allow the recipient genomes to express symbiotic traits are unknown. Here, we report on the experimental evolution of a pathogenic Ralstonia solanacearum chimera carrying the symbiotic plasmid of the rhizobium Cupriavidus taiwanensis into Mimosa nodulating and infecting symbionts. Two types of adaptive mutations in the hrpG-controlled virulence pathway of R. solanacearum were identified that are crucial for the transition from pathogenicity towards mutualism. Inactivation of the hrcV structural gene of the type III secretion system allowed nodulation and early infection to take place, whereas inactivation of the master virulence regulator hrpG allowed intracellular infection of nodule cells. Our findings predict that natural selection of adaptive changes in the legume environment following horizontal transfer has been a major driving force in rhizobia evolution and diversification and show the potential of experimental evolution to decipher the mechanisms leading to symbiosis. PMID:20084095

  2. Pathogen resistance of transgenic tobacco plants producing caffeine.

    PubMed

    Kim, Yun-Soo; Sano, Hiroshi

    2008-02-01

    Caffeine (1,3,7-trimethylxanthine) is a typical purine alkaloid, and produced by a variety of plants such as coffee and tea. Its physiological function, however, is not completely understood, but chemical defense against pathogens and herbivores, and allelopathic effects against competing plant species have been proposed. Previously, we constructed transgenic tobacco plants, which produced caffeine up to 5 microg per gram fresh weight of leaves, and showed them to repel caterpillars of tobacco cutworms (Spodoptera litura). In the present study, we found that these transgenic plants constitutively expressed defense-related genes encoding pathogenesis-related (PR)-1a and proteinase inhibitor II under non-stressed conditions. We also found that they were highly resistant against pathogens, tobacco mosaic virus and Pseudomonas syringae. Expression of PR-1a and PR-2 was higher in transgenic plants than in wild-type plants during infection. Exogenously applied caffeine to wild-type tobacco leaves exhibited the similar resistant activity. These results suggested that caffeine stimulated endogenous defense system of host plants through directly or indirectly activating gene expression. This assumption is essentially consistent with the idea of chemical defense, in which caffeine may act as one of signaling molecules to activate defense response. It is thus conceivable that the effect of caffeine is bifunctional; direct interference with pest metabolic pathways, and activation of host defense systems. PMID:18036626

  3. Competition for zinc binding in the host-pathogen interaction

    PubMed Central

    Cerasi, Mauro; Ammendola, Serena; Battistoni, Andrea

    2013-01-01

    Due to its favorable chemical properties, zinc is used as a structural or catalytic cofactor in a very large number of proteins. Despite the apparent abundance of this metal in all cell types, the intracellular pool of loosely bound zinc ions available for biological exchanges is in the picomolar range and nearly all zinc is tightly bound to proteins. In addition, to limit bacterial growth, some zinc-sequestering proteins are produced by eukaryotic hosts in response to infections. Therefore, to grow and multiply in the infected host, bacterial pathogens must produce high affinity zinc importers, such as the ZnuABC transporter which is present in most Gram-negative bacteria. Studies carried in different bacterial species have established that disruption of ZnuABC is usually associated with a remarkable loss of pathogenicity. The critical involvement of zinc in a plethora of metabolic and virulence pathways and the presence of very low number of zinc importers in most bacterial species mark zinc homeostasis as a very promising target for the development of novel antimicrobial strategies. PMID:24400228

  4. Human Pathogens and the Host Cell SUMOylation System

    PubMed Central

    Wimmer, Peter; Schreiner, Sabrina

    2012-01-01

    Since posttranslational modification (PTM) by the small ubiquitin-related modifiers (SUMOs) was discovered over a decade ago, a huge number of cellular proteins have been found to be reversibly modified, resulting in alteration of differential cellular pathways. Although the molecular consequences of SUMO attachment are difficult to predict, the underlying principle of SUMOylation is altering inter- and/or intramolecular interactions of the modified substrate, changing localization, stability, and/or activity. Unsurprisingly, many different pathogens have evolved to exploit the cellular SUMO modification system due to its functional flexibility and far-reaching functional downstream consequences. Although the extensive knowledge gained so far is impressive, a definitive conclusion about the role of SUMO modification during virus infection in general remains elusive and is still restricted to a few, yet promising concepts. Based on the available data, this review aims, first, to provide a detailed overview of the current state of knowledge and, second, to evaluate the currently known common principles/molecular mechanisms of how human pathogenic microbes, especially viruses and their regulatory proteins, exploit the host cell SUMO modification system. PMID:22072786

  5. Evolution of Pathogen Specialisation in a Host Metapopulation: Joint Effects of Host and Pathogen Dispersal

    PubMed Central

    Papaïx, Julien; Burdon, Jeremy J.; Lannou, Christian; Thrall, Peter H.

    2014-01-01

    Metapopulation processes are important determinants of epidemiological and evolutionary dynamics in host-pathogen systems, and are therefore central to explaining observed patterns of disease or genetic diversity. In particular, the spatial scale of interactions between pathogens and their hosts is of primary importance because migration rates of one species can affect both spatial and temporal heterogeneity of selection on the other. In this study we developed a stochastic and discrete time simulation model to specifically examine the joint effects of host and pathogen dispersal on the evolution of pathogen specialisation in a spatially explicit metapopulation. We consider a plant-pathogen system in which the host metapopulation is composed of two plant genotypes. The pathogen is dispersed by air-borne spores on the host metapopulation. The pathogen population is characterised by a single life-history trait under selection, the infection efficacy. We found that restricted host dispersal can lead to high amount of pathogen diversity and that the extent of pathogen specialisation varied according to the spatial scale of host-pathogen dispersal. We also discuss the role of population asynchrony in determining pathogen evolutionary outcomes. PMID:24853675

  6. The spread of pathogens through trade in aquatic animals and their products.

    PubMed

    Rodgers, C J; Mohan, C V; Peeler, E J

    2011-04-01

    It is well known that the transboundary spread of infectious diseases is aided by trade in live animals and the consequences can be severe if, as a result, a pathogen broadens its host range to new species. Trade in aquatic animal species is increasing, and aquaculture is also expanding to meet the growing human population's demands for animal protein. Moreover, it is clear that aquaculture has created potential new pathways by which pathogens and diseases may be introduced or spread to new areas. The risk of pathogen transfer is generally considered greater for the movement of live aquatic animals than for the movement of processed and dead products. The currently available health standards support the concept of minimising the risk of disease and pathogen incursion while, at the same time, avoiding unjustifiable or unnecessary impediments to trade. Nevertheless, the international spread of diseases through the movement of animals still occurs, despite these standards. Consequently, this paper considers the evidence linking international trade in aquatic animals and aquatic animal-derived products with the transmission and spread of diseases. The authors provide examples of pathogen transfer leading to disease spread and considerthe situation of emerging diseases, as well as the need for a holistic approach to deal with risk-based threats at their source. PMID:21809767

  7. Haemoglobin modulates salicylate and jasmonate/ethylene-mediated resistance mechanisms against pathogens

    PubMed Central

    Mur, Luis A. J.

    2012-01-01

    Nitric oxide (NO) plays a role in defence against hemibiotrophic pathogens mediated by salicylate (SA) and also necrotrophic pathogens influenced by jasmonate/ethylene (JA/Et). This study examined how NO-oxidizing haemoglobins (Hb) encoded by GLB1, GLB2, and GLB3 in Arabidopsis could influence both defence pathways. The impact of Hb on responses to the hemibiotrophic Pseudomonas syringae pathovar tomato (Pst) AvrRpm1 and the necrotrophic Botrytis cinerea were investigated using glb1, glb2, and glb3 mutant lines and also CaMV 35S GLB1 and GLB2 overexpression lines. In glb1, but not glb2 and glb3, increased resistance was observed to both pathogens but was compromised in the 35S-GLB1. A quantum cascade laser-based sensor measured elevated NO production in glb1 infected with Pst AvrRpm1 and B. cinerea, which was reduced in 35S-GLB1 compared to Col-0. SA accumulation was increased in glb1 and reduced in 35S-GLB1 compared to controls following attack by Pst AvrRpm1. Similarly, JA and Et levels were increased in glb1 but decreased in 35S-GLB1 in response to attack by B. cinerea. Quantitative PCR assays indicated reduced GLB1 expression during challenge with either pathogen, thus this may elevate NO concentration and promote a wide-ranging defence against pathogens. PMID:22641422

  8. Susceptibility of Intact Germinating Arabidopsis thaliana to Human Fungal Pathogens Cryptococcus neoformans and C. gattii

    PubMed Central

    Park, Yoon-Dong

    2013-01-01

    The fungus Cryptococcus contributes a large global burden of infectious death in both HIV-infected and healthy individuals. As Cryptococcus is an opportunistic pathogen, much of the evolutionary pressure shaping virulence occurs in environments in contact with plants and soil. The present studies investigated inoculation of intact seeds of the common weed Arabidopsis thaliana with fungal cells over a 21-day period. C. gattii was the more virulent plant pathogen, resulting in disrupted germination as well as increased stem lodging, fungal burden, and plant tissue colocalization. C. neoformans was a less virulent plant pathogen but exhibited prolonged tissue residence within the cuticle and vascular spaces. Arabidopsis mutants of the PRN1 gene, which is involved in abiotic and biotic signaling affecting phenylalanine-derived flavonoids, showed altered susceptibility to cryptoccocal infections, suggesting roles for this pathway in cryptococcal defense. The fungal virulence factor laccase was also implicated in plant pathogenesis, as a cryptococcal lac1? strain was less virulent than wild-type fungi and was unable to colonize seedlings. In conclusion, these studies expand knowledge concerning the ecological niche of Cryptococcus by demonstrating the pathogenic capacity of the anamorphic form of cryptococcal cells against healthy seedlings under physiologically relevant conditions. In addition, an important role of laccase in plant as well as human virulence may suggest mechanisms for laccase retention and optimization during evolution of this fungal pathogen. PMID:23435895

  9. Cgl-SLT2 is required for appressorium formation, sporulation and pathogenicity in Colletotrichum gloeosporioides

    PubMed Central

    Yong, H.Y.; Bakar, F.D.A.; Illias, R.M.; Mahadi, N.M.; Murad, A.M.A.

    2013-01-01

    The mitogen-activated protein (MAP) kinase pathways has been implicated in the pathogenicity of various pathogenic fungi and plays important roles in regulating pathogenicity-related morphogenesis. This work describes the isolation and characterization of MAP kinase gene, Cgl-SLT2, from Colletotrichum gloeosporioides. A DNA sequence, including 1,633 bp of Cgl-SLT2 open-reading frame and its promoter and terminator regions, was isolated via DNA walking and cloned. To analyze gene function, a gene disruption cassette containing hygromycin-resistant gene was constructed, and Cgl-SLT2 was inactivated via gene deletion. Analysis on Cgl-slt2 mutant revealed a defect in vegetative growth and sporulation as compared to the wild-type strain. When grown under nutrient-limiting conditions, hyperbranched hyphal morphology was observed in the mutant. Conidia induction for germination on rubber wax-coated hard surfaces revealed no differences in the percentage of conidial germination between the wild-type and Cgl-slt2 mutant. However, the percentage of appressorium formation in the mutant was greatly reduced. Bipolar germination in the mutant was higher than in the wild-type at 8-h post-induction. A pathogenicity assay revealed that the mutant was unable to infect either wounded or unwounded mangoes. These results suggest that the Cgl-SLT2 MAP kinase is required for C. gloeosporioides conidiation, polarized growth, appressorium formation and pathogenicity. PMID:24688518

  10. Myocyte Adrenoceptor Signaling Pathways

    NSDL National Science Digital Library

    Yang Xiang (Stanford Medical Center; Department of Molecular and Cellular Physiology)

    2003-06-06

    Adrenoceptors (ARs), members of the G proteinâ??coupled receptor superfamily, form the interface between the sympathetic nervous system and the cardiovascular system, with integral roles in the rapid regulation of myocardial function. However, in heart failure, chronic catecholamine stimulation of adrenoceptors has been linked to pathologic cardiac remodeling, including myocyte apoptosis and hypertrophy. In cardiac myocytes, activation of AR subtypes results in coupling to different G proteins and induction of specific signaling pathways, which is partly regulated by the subtype-specific distribution of receptors in plasma membrane compartments containing distinct complexes of signaling molecules. The Connections Maps of the Adrenergic and Myocyte Adrenergic Signaling Pathways bring into focus the specific signaling pathways of individual AR subtypes and their relevant functions in vivo.

  11. Predicting pathogen transport and risk of infection from land-applied biosolids

    NASA Astrophysics Data System (ADS)

    Olson, M. S.; Teng, J.; Kumar, A.; Gurian, P.

    2011-12-01

    Biosolids have been recycled as fertilizer to sustainably improve and maintain productive soils and to stimulate plant growth for over forty years, but may contain low levels of microbial pathogens. The Spreadsheet Microbial Assessment of Risk: Tool for Biosolids ("SMART Biosolids") is an environmental transport, exposure and risk model that compiles knowledge on the occurrence, environmental dispersion and attenuation of biosolids-associated pathogens to estimate microbial risk from biosolids land application. The SMART Biosolids model calculates environmental pathogen concentrations and assesses risk associated with exposure to pathogens from land-applied biosolids through five pathways: 1) inhalation of aerosols from land application sites, 2) consumption of groundwater contaminated by land-applied biosolids, 3) direct ingestion of biosolids-amended soils, 4) ingestion of plants contaminated by land-applied biosolids, and 5) consumption of surface water contaminated by runoff from a land application site. The SMART Biosolids model can be applied under a variety of scenarios, thereby providing insight into effective management practices. This study presents example results of the SMART Biosolids model, focusing on the groundwater and surface water pathways, following biosolids application to a typical site in Michigan. Volumes of infiltration and surface water runoff are calculated following a 100-year storm event. Pathogen transport and attenuation through the subsurface and via surface runoff are modeled, and pathogen concentrations in a downstream well and an adjacent pond are calculated. Risks are calculated for residents of nearby properties. For a 100-year storm event occurring immediately after biosolids application, the surface water pathway produces risks that may be of some concern, but best estimates do not exceed the bounds of what has been considered acceptable risk for recreational water use (Table 1); groundwater risks are very uncertain and at the upper bound may exceed both drinking water and recreational standards, but these risks would be associated with very shallow groundwater (depth of 3 feet), which would not typically be used as a potable water source. Comparisons across pathogens are presented, as are the effects of different site management practices.
    Risk from Surface Water Recreational Swimming Following a 1 in 100 Year Storm Event Values displayed are based on nominal input parameter values with 5-95th percentiles of a Monte Carlo simulation given in parentheses. NA - not available as value was below reporting threshold of 10-2

  12. Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica

    PubMed Central

    Belmonte, Rodrigo; Löbach, Lars; Christie, James; van den Ackerveken, Guido; Bottin, Arnaud; Bulone, Vincent; Díaz-Moreno, Sara M.; Dumas, Bernard; Fan, Lin; Gaulin, Elodie; Govers, Francine; Grenville-Briggs, Laura J.; Horner, Neil R.; Levin, Joshua Z.; Mammella, Marco; Meijer, Harold J. G.; Morris, Paul; Nusbaum, Chad; Oome, Stan; Phillips, Andrew J.; van Rooyen, David; Rzeszutek, Elzbieta; Saraiva, Marcia; Secombes, Chris J.; Seidl, Michael F.; Snel, Berend; Stassen, Joost H. M.; Sykes, Sean; Tripathy, Sucheta; van den Berg, Herbert; Vega-Arreguin, Julio C.; Wawra, Stephan; Young, Sarah K.; Zeng, Qiandong; Dieguez-Uribeondo, Javier; Russ, Carsten; Tyler, Brett M.; van West, Pieter

    2013-01-01

    Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians, crustaceans, fish and insects, resulting in major losses in aquaculture and damage to aquatic ecosystems. We have sequenced the 63 Mb genome of the fresh water fish pathogen, Saprolegnia parasitica. Approximately 1/3 of the assembled genome exhibits loss of heterozygosity, indicating an efficient mechanism for revealing new variation. Comparison of S. parasitica with plant pathogenic oomycetes suggests that during evolution the host cellular environment has driven distinct patterns of gene expansion and loss in the genomes of plant and animal pathogens. S. parasitica possesses one of the largest repertoires of proteases (270) among eukaryotes that are deployed in waves at different points during infection as determined from RNA-Seq data. In contrast, despite being capable of living saprotrophically, parasitism has led to loss of inorganic nitrogen and sulfur assimilation pathways, strikingly similar to losses in obligate plant pathogenic oomycetes and fungi. The large gene families that are hallmarks of plant pathogenic oomycetes such as Phytophthora appear to be lacking in S. parasitica, including those encoding RXLR effectors, Crinkler's, and Necrosis Inducing-Like Proteins (NLP). S. parasitica also has a very large kinome of 543 kinases, 10% of which is induced upon infection. Moreover, S. parasitica encodes several genes typical of animals or animal-pathogens and lacking from other oomycetes, including disintegrins and galactose-binding lectins, whose expression and evolutionary origins implicate horizontal gene transfer in the evolution of animal pathogenesis in S. parasitica. PMID:23785293

  13. Distinctive expansion of potential virulence genes in the genome of the oomycete fish pathogen Saprolegnia parasitica.

    PubMed

    Jiang, Rays H Y; de Bruijn, Irene; Haas, Brian J; Belmonte, Rodrigo; Löbach, Lars; Christie, James; van den Ackerveken, Guido; Bottin, Arnaud; Bulone, Vincent; Díaz-Moreno, Sara M; Dumas, Bernard; Fan, Lin; Gaulin, Elodie; Govers, Francine; Grenville-Briggs, Laura J; Horner, Neil R; Levin, Joshua Z; Mammella, Marco; Meijer, Harold J G; Morris, Paul; Nusbaum, Chad; Oome, Stan; Phillips, Andrew J; van Rooyen, David; Rzeszutek, Elzbieta; Saraiva, Marcia; Secombes, Chris J; Seidl, Michael F; Snel, Berend; Stassen, Joost H M; Sykes, Sean; Tripathy, Sucheta; van den Berg, Herbert; Vega-Arreguin, Julio C; Wawra, Stephan; Young, Sarah K; Zeng, Qiandong; Dieguez-Uribeondo, Javier; Russ, Carsten; Tyler, Brett M; van West, Pieter

    2013-06-01

    Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians, crustaceans, fish and insects, resulting in major losses in aquaculture and damage to aquatic ecosystems. We have sequenced the 63 Mb genome of the fresh water fish pathogen, Saprolegnia parasitica. Approximately 1/3 of the assembled genome exhibits loss of heterozygosity, indicating an efficient mechanism for revealing new variation. Comparison of S. parasitica with plant pathogenic oomycetes suggests that during evolution the host cellular environment has driven distinct patterns of gene expansion and loss in the genomes of plant and animal pathogens. S. parasitica possesses one of the largest repertoires of proteases (270) among eukaryotes that are deployed in waves at different points during infection as determined from RNA-Seq data. In contrast, despite being capable of living saprotrophically, parasitism has led to loss of inorganic nitrogen and sulfur assimilation pathways, strikingly similar to losses in obligate plant pathogenic oomycetes and fungi. The large gene families that are hallmarks of plant pathogenic oomycetes such as Phytophthora appear to be lacking in S. parasitica, including those encoding RXLR effectors, Crinkler's, and Necrosis Inducing-Like Proteins (NLP). S. parasitica also has a very large kinome of 543 kinases, 10% of which is induced upon infection. Moreover, S. parasitica encodes several genes typical of animals or animal-pathogens and lacking from other oomycetes, including disintegrins and galactose-binding lectins, whose expression and evolutionary origins implicate horizontal gene transfer in the evolution of animal pathogenesis in S. parasitica. PMID:23785293

  14. Metabolic Pathways of Biochemistry

    NSDL National Science Digital Library

    George Washington University provides an online reference of the major metabolic pathways for biochemistry students and scientists. Students can learn about carbohydrate, lipid, and energy metabolism with the help of two- and three-dimensional graphics. The website offers representations of generalized organic reactions to illustrate how to convert one functional group to another group. Users can also find a list of over 250 common abbreviations used in biochemistry. Biochemistry students having difficulty conceiving the dimensionality of metabolic pathways will benefit from the materials at this web site.

  15. Signaling pathways required for macrophage scavenger receptor-mediated phagocytosis: analysis by scanning cytometry

    Microsoft Academic Search

    Timothy H Sulahian; Amy Imrich; Glen DeLoid; Aaron R Winkler; Lester Kobzik

    2008-01-01

    BACKGROUND: Scavenger receptors are important components of the innate immune system in the lung, allowing alveolar macrophages to bind and phagocytose numerous unopsonized targets. Mice with genetic deletions of scavenger receptors, such as SR-A and MARCO, are susceptible to infection or inflammation from inhaled pathogens or dusts. However, the signaling pathways required for scavenger receptor-mediated phagocytosis of unopsonized particles have

  16. Suppression of the TRIF-dependent signaling pathway of Toll-like receptors by luteolin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toll-like receptors (TLRs) play an important role in induction of immune and inflammatory responses by recognizing invading pathogens. TLRs have two major downstream signaling pathways activated through the interaction with adaptor molecules, MyD88 and TRIF, leading to the expression of proinflammat...

  17. Starter unit specificity directs genome mining of polyketide synthase pathways in fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Search of the protein database with the aflatoxin pathway polyketide synthase (PKS) revealed putative PKSs in the pathogenic fungi Coccidioides immitis and Coccidioides posadasii that could require partnerships with a pair of fatty acid synthase (FAS) subunits for the biosynthesis of fatty acid-poly...

  18. Repression of the Auxin Response Pathway Increases Arabidopsis Susceptibility to Necrotrophic Fungi

    Microsoft Academic Search

    Francisco Llorente; Paul Muskett; A. Sanchez-Vallet; G. Lopez; B. Ramos; C. Sanchez-Rodriguez; L. Jorda; Jane Parker; Antonio Molina

    2008-01-01

    In plants, resistance to necrotrophic pathogens depends on the interplay between different hormone sys- tems, such as those regulated by salicylic acid (SA), jasmonic acid (JA), ethylene, and abscisic acid. Repression of auxin signaling by the SA pathway was recently shown to contribute to antibacterial resistance. Here, we demonstrate that Arabidopsis auxin signaling mutants axr1, axr2, and axr6 that have

  19. Pathogenic mechanisms of Helicobacter pylori.

    PubMed

    Dunn, B E

    1993-03-01

    There is general agreement that motility, urease activity, and association with gastric mucosal cells are important virulence factors of H. pylori. Urease activity is perhaps the best characterized of these factors. Presumably, urease activity creates a "cloud" of ammonia around the bacterium, thus neutralizing the lethal effects of gastric acid. Motility allows the bacterium to penetrate the mucus layer and promotes specific association of the bacteria with epithelial cells, further allowing evasion of gastric acidity. The association between gastrin levels and H. pylori infection is currently the most thoroughly studied feature relating to pathogenesis in vivo. Prolonged hypergastrinemia associated with H. pylori infection may contribute to increased parietal cell mass and chronically increased secretion of gastric acid; however, long-term studies are needed to validate this hypothesis. The identification of mucosal gamma delta T cells and immunologic cross-reactivity between H. pylori and gastric cells implies that the immune response contributes significantly to the pathogenesis of H. pylori. The role of the immune system in modulating H. pylori infection requires further study. Although many putative pathogenic factors have been identified on the basis of in vitro phenomena alone, their significance in vivo is not known. Ultimately, it will be necessary to evaluate the significance of these factors in animal models by using isogenic strains of H. pylori that differ only in a single genotypic characteristic. PMID:8449569

  20. Pathogenicity and virulence: another view.

    PubMed Central

    Isenberg, H D

    1988-01-01

    The concepts of pathogenicity and virulence have governed our perception of microbial harmfulness since the time of Pasteur and Koch. These concepts resulted in the recognition and identification of numerous etiological agents and provided natural and synthetic agents effective in therapy and prevention of diseases. However, Koch's postulates--the premier product of this view--place the onus of harmfulness solely on the microbial world. Our recent experiences with polymicrobic and nosocomial infections, legionellosis, and acquired immunodeficiency syndrome point to the host as the major determinant of disease. The principles of parasitism, enunciated by Theobold Smith, approximate more accurately the disturbances of the host-parasite equilibrium we designate as infection. Many complex attributes of microbial anatomy and physiology have been obscured by our dependency on the pure-culture technique. For example, bacterial attachment organelles and the production of exopolysaccharides enable microorganisms to interact with mammalian glycocalyces and specific receptors. In addition, selection, through the use of therapeutic agents, aids in the progression of environmental organisms to members of the intimate human biosphere, with the potential to complicate the recovery of patients. These factors emphasize further the pivotal significance of host reactions in infections. Parasitism, in its negative aspects, explains the emergence of "new" infections that involve harm to more than host organs and cells: we may encounter subtler infections that reveal parasitic and host cell nucleic acid interactions in a form of genomic parasitism. PMID:3060244

  1. Infectious pathogens and hematologic malignancy.

    PubMed

    Sadrzadeh, Hossein; Abtahi, Seyed M; Fathi, Amir T

    2012-12-01

    Infectious pathogens have been linked to the genesis of malignancy in a variety of different settings. Initial studies in virology led to the important discovery of key genetic alterations underlying common malignancies, and further, lent support to the notion that malignancy can be promoted by the process of viral infection and cellular transformation. In this review, we summarize a series of hematologic malignancies with derivations from and associations with infectious organisms. Among these are a variety of lymphomas, including Hodgkin's lymphoma (Hodgkin's disease), Burkitt lymphoma, and a host of other non-Hodgkin's lymphomas. Through innovative and ground-breaking studies, some of these malignancies have been directly linked to viral infection, such as the Epstein-Barr virus (EBV), while others have been merely associated with infection through epidemiologic studies and case-reports. Some malignancies have been demonstrated to be caused by viral infection, such as adult T-cell leukemia and lymphoma (ATLL), which is caused by the human T cell lymphotropic virus type I (HTLV-I), in certain endemic area. In the future, additional malignant states may be found to be associated with infectious etiology, which could allow for novel approaches to prevention and treatment. PMID:23272694

  2. New and emerging yeast pathogens.

    PubMed Central

    Hazen, K C

    1995-01-01

    The most common yeast species that act as agents of human disease are Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Cryptococcus neoformans. The incidence of infections by other yeasts has increased during the past decade. The most evident emerging pathogens are Malassezia furfur, Trichosporon beigelii, Rhodotorula species, Hansenula anomala, Candida lusitaniae, and Candida krusei. Organisms once considered environmental contaminants or only industrially important, such as Candida utilis and Candida lipolytica, have now been implicated as agents of fungemia, onychomycosis, and systemic disease. The unusual yeasts primarily infect immunocompromised patients, newborns, and the elderly. The role of central venous catheter removal and antifungal therapy in patient management is controversial. The antibiograms of the unusual yeasts range from resistant to the most recent azoles and amphotericin B to highly susceptible to all antifungal agents. Current routine methods for yeast identification may be insufficient to identify the unusual yeasts within 2 days after isolation. The recognition of unusual yeasts as agents of sometimes life-threatening infection and their unpredictable antifungal susceptibilities increase the burden on the clinical mycology laboratory to pursue complete species identification and MIC determinations. Given the current and evolving medical practices for management of seriously ill patients, further evaluations of the clinically important data about these yeasts are needed. PMID:8665465

  3. Immune response to a pathogen in corals.

    PubMed

    Ruiz-Diaz, Claudia Patricia; Toledo-Hernández, Carlos; Sabat, Alberto M; Marcano, Mariano

    2013-09-01

    The sea fan coral (Gorgonia ventalina), one of the most abundant gorgonians in the tropical and subtropical Atlantic waters, have suffered several diseases that have diminished its abundance throughout their range. In this study, we present a model that analyzes the capacity of G. ventalina to eradicate a micro-pathogen under three immune responses: strong, moderate, and very weak. The model assumes that: (1) polyps are the main unit of the coral; (2) the population of polyps is homogeneously distributed; and (3) the immune system is activated by a signal. When an endosymbiont exceeds a density threshold, it becomes pathogenic, increasing polyp mortality. As a consequence, the colony emits a signal to its stem cells to differentiate into phagocytic and humoral cells, both of which combat the pathogen. Given a strong immune response, the pathogen is rapidly eradicated by the immune cells, and the coral polyp population returns to an equilibrium state. With a moderate immune response, polyps and pathogen coexist, but the maximum capacity of polyp density is never reached. An immunologically compromised colony offering a weak immune response is unable to stop pathogen growth, and the colony dies. This analysis suggests an alternative explanation for the spatial and temporal variability in disease incidence and mortality, which is based on the strength of the immune system of hosts rather than the virulence of the pathogen. PMID:23659851

  4. An algorithm for modularization of MAPK and calcium signaling pathways: comparative analysis among different species.

    PubMed

    Nayak, Losiana; De, Rajat K

    2007-12-01

    Signaling pathways are large complex biochemical networks. It is difficult to analyze the underlying mechanism of such networks as a whole. In the present article, we have proposed an algorithm for modularization of signal transduction pathways. Unlike studying a signaling pathway as a whole, this enables one to study the individual modules (less complex smaller units) easily and hence to study the entire pathway better. A comparative study of modules belonging to different species (for the same signaling pathway) has been made, which gives an overall idea about development of the signaling pathways over the taken set of species of calcium and MAPK signaling pathways. The superior performance, in terms of biological significance, of the proposed algorithm over an existing community finding algorithm of Newman [Newman MEJ. Modularity and community structure in networks. Proc Natl Acad Sci USA 2006;103(23):8577-82] has been demonstrated using the aforesaid pathways of H. sapiens. PMID:17591461

  5. The Interaction of Human Enteric Pathogens with Plants

    PubMed Central

    Lim, Jeong-A; Lee, Dong Hwan; Heu, Sunggi

    2014-01-01

    There are an increasing number of outbreaks of human pathogens related to fresh produce. Thus, the growth of human pathogens on plants should be explored. Human pathogens can survive under the harsh environments in plants, and can adhere and actively invade plants. Plant-associated microbiota or insects contribute to the survival and transmission of enteric pathogens in plants. Human enteric pathogens also trigger plant innate immunity, but some pathogens–such as Salmonella–can overcome this defense mechanism. PMID:25288993

  6. Microfluidic Systems for Pathogen Sensing: A Review

    PubMed Central

    Mairhofer, Jürgen; Roppert, Kriemhilt; Ertl, Peter

    2009-01-01

    Rapid pathogen sensing remains a pressing issue today since conventional identification methodsare tedious, cost intensive and time consuming, typically requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays and microfluidic biochips, offer real alternatives capable of filling this technological gap. In particular microfluidic biochips make the development of fast, sensitive and portable diagnostic tools possible, thus promising rapid and accurate detection of a variety of pathogens. This paper will provide a broad overview of the novel achievements in the field of pathogen sensing by focusing on methods and devices that compliment microfluidics. PMID:22408555

  7. Real Time Detection of Foodborne Pathogens

    NASA Astrophysics Data System (ADS)

    Velusamy, V.; Arshak, K.; Korostynka, O.; Vaseashta, Ashok; Adley, C.

    Contamination of foods by harmful bacteria by natural events or malicious intent poses a serious threat to public health and safety. This review introduces current technologies in detecting pathogens in food and foodborne illnesses. Causes of foodborne diseases and trends impacting foodborne diseases such as globalization and changes in micro-organisms, human populations, lifestyles, and climates are addressed. In addition, a review of the limitations in detecting pathogens with conventional technologies is presented. Finally, a review of nanostructured and nanomaterials based sensing technologies by pathogen, detection limits, and advantages is described.

  8. Bacteriophages as biocontrol agents of food pathogens.

    PubMed

    Mahony, Jennifer; McAuliffe, Olivia; Ross, R Paul; van Sinderen, Douwe

    2011-04-01

    Bacteriophages have long been recognized for their potential as biotherapeutic agents. The recent approval for the use of phages of Listeria monocytogenes for food safety purposes has increased the impetus of phage research to uncover phage-mediated applications with activity against other food pathogens. Areas of emerging and growing significance, such as predictive modelling and genomics, have shown their potential and impact on the development of new technologies to combat food pathogens. This review will highlight recent advances in the research of phages that target food pathogens and that promote their use in biosanitation, while it will also discuss its limitations. PMID:21115341

  9. A Pathway Idea for Model Building

    PubMed Central

    Mathai, A.M.; Moschopoulos, Panagis

    2013-01-01

    Models, mathematical or stochastic, which move from one functional form to another through pathway parameters, so that in between stages can be captured, are examined in this article. Models which move from generalized type-1 beta family to type-2 beta family, to generalized gamma family to generalized Mittag-Leffler family to Lévy distributions are examined here. It is known that one can likely find an approximate model for the data at hand whether the data are coming from biological, physical, engineering, social sciences or other areas. Different families of functions are connected through the pathway parameters and hence one will find a suitable member from within one of the families or in between stages of two families. Graphs are provided to show the movement of the different models showing thicker tails, thinner tails, right tail cut off etc. PMID:24883223

  10. Cytokine production and signaling pathways in respiratory virus infection

    PubMed Central

    Kimura, Hirokazu; Yoshizumi, Masakazu; Ishii, Haruyuki; Oishi, Kazunori; Ryo, Akihide

    2013-01-01

    It has been confirmed that respiratory virus infections can induce abberant cytokine production in the host. These cytokines may be associated with both elimination of the virus and complications in the host, such as virus-induced asthma. Representative host defense mechanisms against pathogens, including bacteria and viruses, are mediated by the innate immune system. Cells of the innate immune system express essential molecules, namely pattern recognition receptors (PRRs), such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and retinoic acid-inducible gene-I-like receptors. These PRRs can recognize components of pathogens such as bacterial lipopolysaccharide, viral antigens, and their genomes (DNA and RNA). Furthermore, PRRs activate various signaling pathways resulting in cytokine production against pathogen infection. However, the exact mechanisms remain unknown. In this review, we mainly focus on the representative mechanisms of cytokine production through PRRs and signaling pathways due to virus infections, including respiratory virus infections. In addition, we describe the relationships between respiratory infections and virus-induced asthma. PMID:24062733

  11. The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

    PubMed Central

    Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

    2008-01-01

    Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584

  12. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    PubMed

    Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

    2008-12-01

    Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584

  13. Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria

    PubMed Central

    Bravo-Patiño, Alejandro; Baizabal-Aguirre, Víctor M.

    2014-01-01

    Early sensing of pathogenic bacteria by the host immune system is important to develop effective mechanisms to kill the invader. Microbial recognition, activation of signaling pathways, and effector mechanisms are sequential events that must be highly controlled to successfully eliminate the pathogen. Host recognizes pathogens through pattern-recognition receptors (PRRs) that sense pathogen-associated molecular patterns (PAMPs). Some of these PRRs include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid-inducible gene-I- (RIG-I-) like receptors (RLRs), and C-type lectin receptors (CLRs). TLRs and NLRs are PRRs that play a key role in recognition of extracellular and intracellular bacteria and control the inflammatory response. The activation of TLRs and NLRs by their respective ligands activates downstream signaling pathways that converge on activation of transcription factors, such as nuclear factor-kappaB (NF-?B), activator protein-1 (AP-1) or interferon regulatory factors (IRFs), leading to expression of inflammatory cytokines and antimicrobial molecules. The goal of this review is to discuss how the TLRs and NRLs signaling pathways collaborate in a cooperative or synergistic manner to counteract the infectious agents. A deep knowledge of the biochemical events initiated by each of these receptors will undoubtedly have a high impact in the design of more effective strategies to control inflammation. PMID:25525300

  14. Developmental pathways of anthozoans

    Microsoft Academic Search

    D. G. Fautin

    1991-01-01

    Stage of propagule release from female parent, and site of development and nutritive mode of embryo are the factors used here to define developmental pathways of anthozoans. Nearly every possible combination of variables of the 3 factors exists, forming a mosaic. Further, a larva may experience serially more than one development site, and may derive nutrition serially or simultaneously from

  15. Environmental Science: Sample Pathway

    E-print Network

    Goldberg, Bennett

    Environmental Science: Sample Pathway Semester I Semester II Freshman Year CGS Core CGS Core GE 100 Intro to Env Science ES 105 Env Earth Science Sophomore Year CGS Core (CGS NS201 will fulfill CAS BI107 & 124) MA 115 Statistics Summer Environmental Internship Junior Year CH 171 Chem for Health Sciences CH

  16. SPARTANADVENTURES SPARTAN PATHWAYS

    E-print Network

    and I'd love for you to join us in 2015. From the ever-popular European destinations to wonderful of Michigan. We are pleased to be offering the tour again twice in 2015. If you love dogs, nature and enjoy Waterways and Canals of Holland & Belgium Italy Lifestyle Explorations Alumni Campus in Sicily Pathway

  17. Pathways to School Success

    ERIC Educational Resources Information Center

    University of Pittsburgh Office of Child Development, 2012

    2012-01-01

    In 2006, the University of Pittsburgh Office of Child Development began implementing a multi-year school readiness project in several area schools. Evidence from both research and the field point to several key elements that foster school readiness and create pathways to school success for all children. This paper presents components of a…

  18. Enteric pathogens and cellular transformation: bridging the gaps.

    PubMed

    Umar, Shahid

    2014-08-30

    Cancer patients in general, either due to the nature of their underlying illness or because of being on chemotherapeutic regimens, are at increased risk of infection. Indeed, microbes can exploit the innate plasticity of the epithelial cells to promote their trans-differentiation into a mesenchymal phenotype in a process called epithelial-to-mesenchymal transition (EMT). This process as well as the reverse, mesenchymal-epithelial transition, occurs repeatedly during normal embryonic development and is recapitulated during pathologies such as tissue fibrosis or tumor metastasis. Multiple signaling pathways including TGF?, Wnt and Notch working together with transcription factors such as Slug, Snail, Twist, Zeb1 and 2 suppress E-cadherin, induce EMT and result in loss of cell-cell adhesion, increased tumor progression and migration. In addition, in approximately 20% of all cases, microbial organisms including pathobionts of the commensal microbiota, have been implicated in inflammatory processes that promote tumor growth. Thus, the dynamic process of EMT serves to enhance tumor progression and is also involved in the generation of cancer stem cells (CSCs) across multiple organ systems including colon cancer. Suffice to say, EMT and CSC molecular pathways activated by pathogens, may represent a unique therapeutic alternative to conventional anti-neoplastic strategy to mitigate early stage metastasis and/or frank malignancy. PMID:25216513

  19. The microbiome and emerging pathogens in cystic fibrosis and non-cystic fibrosis bronchiectasis.

    PubMed

    Green, Heather; Jones, Andrew M

    2015-04-01

    Chronic pulmonary sepsis is the predominant cause of morbidity for patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously it was thought that respiratory infection in these patients was mostly limited to a very small number of typical pathogens; however, in recent years there have been increasing reports of infection with other emerging potential pathogens including Burkholderia, Stenotrophomonas, Achromobacter, Ralstonia, Pandoraea, nontuberculous mycobacteria, and fungal species. Furthermore, culture-independent methodologies have established that the lungs of patients with CF and non-CF bronchiectasis comprise mixed microbiological communities of aerobic and anaerobic bacteria, fungal and viral species, collectively referred to as the lung microbiome. This article addresses the clinical relevance of emerging pathogens and the lung microbiome in CF and non-CF bronchiectasis. PMID:25826590

  20. Jasmonate Signaling Pathway

    NSDL National Science Digital Library

    Robin Liechti (University of Lausanne; Gene Expression Laboratory and Faculty of Biology and Medicine REV)

    2006-02-14

    Jasmonates in plants are cyclic fatty acid–derived regulators structurally similar to prostaglandins in metazoans. These chemicals mediate many of plants' transcriptional responses to wounding and pathogenesis by acting as potent regulators for the expression of numerous frontline immune response genes, including those for defensins and antifungal proteins. Additionally, the pathway is critical for fertility. Ongoing genetic screens and protein-protein interaction assays are identifying components of the canonical jasmonate signaling pathway. A massive molecular machine, based on two multiprotein complexes, SCFCOI1 and the COP9 signalosome (CNS), plays a central role in jasmonate signaling. This machine functions in vivo as a ubiquitin ligase complex, probably targeting regulatory proteins, some of which are expected to be transcriptional repressors. Some defense-related mediators, notably salicylic acid, antagonize jasmonates in controlling the expression of many genes. In Arabidopsis, NONEXPRESSOR OF PR GENES (NPR1) mediates part of this interaction, with another layer of control provided further downstream by the mitogen-activated protein kinase (MAPK) homolog MPK4. Numerous other interpathway connections influence the jasmonate pathway. Insights from Arabidopsis have shown that an allele of the auxin signaling gene AXR1, for example, reduces the sensitivity of plants to jasmonate. APETALA2 (AP2)-domain transcription factors, such as ETHYLENE RESPONSE FACTOR 1 (ERF1), link the jasmonate pathway to the ethylene signaling pathway. As progress in characterizing several new mutants (some of which are hypersensitive to jasmonic acid) augments our understanding of jasmonate signaling, the Connections Map will be updated to include this new information.