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1

FY2003 LDRD Final Annual Report Article: Pathogen Pathway Project  

SciTech Connect

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.

Fitch, J P; McCutchen-Maloney, S L

2003-11-10

2

Review article Melatonin synthesis pathway  

E-print Network

- O-methyltransferase/ pinéale/ rétine 1. INTRODUCTION The production of the pineal hormone melatoninReview article Melatonin synthesis pathway: circadian regulation of the genes encoding the key three enzymes of the melatonin synthesis pathway (tryptophan hydroxylase (TPH), arylalkylamine

Boyer, Edmond

3

ORIGINAL ARTICLE Moths that Vector a Plant Pathogen also Transport  

E-print Network

ORIGINAL ARTICLE Moths that Vector a Plant Pathogen also Transport Endophytic Fungi Abstract Claviceps paspali, a common fungal pathogen of Paspalum grasses, attracts moth vectors Fusarium species that may negatively influence C. paspali fitness. We examined the potential for moths

Arnold, A. Elizabeth

4

Original article Enteric bacterial pathogen detection in southern sea otters  

E-print Network

Original article Enteric bacterial pathogen detection in southern sea otters (Enhydra lutris nereis for nearly a century, California's sea otters have been slow to recover, in part due to exposure to fecally and dead sea otters from California for specific enteric bacterial pathogens (Campylobacter, Salmonella

Paris-Sud XI, Université de

5

Evolution of siderophore pathways in human pathogenic bacteria.  

PubMed

Ornibactin and malleobactin are hydroxamate siderophores employed by human pathogenic bacteria belonging to the genus Burkholderia. Similarities in their structures and corresponding biosynthesis gene clusters strongly suggest an evolutionary relationship. Through gene coexpression and targeted gene manipulations, the malleobactin pathway was successfully morphed into an ornibactin assembly line. Such an evolutionary-guided approach has been unprecedented for nonribosomal peptide synthetases. Furthermore, the timing of amino acid acylation before peptide assembly, the absolute configuration of the ornibactin side chain, and the function of the acyl transferase were elucidated. Beyond providing a proof of principle for the rational design of siderophore pathways, a compelling model for the evolution of virulence traits is presented. PMID:24707815

Franke, Jakob; Ishida, Keishi; Hertweck, Christian

2014-04-16

6

Co-evolution and exploitation of host cell signaling pathways by bacterial pathogens  

Microsoft Academic Search

Bacterial pathogens have evolved by combinations of gene acquisition, deletion, and modification, which increases their fitness. Additionally, bacteria are able to evolve in quantum leaps via the ability to promiscuously acquire new genes. Many bacterial pathogens especially Gram-negative enteric pathogens have evolved mechanisms by which to subvert signal transduction pathways of eukaryotic cells by expressing genes that mimic

Stephanie R. Shames; Sigrid D. Auweter; B. Brett Finlay

2009-01-01

7

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

PubMed Central

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

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

2014-01-01

8

Original article Signaling pathways involved in liver injury  

E-print Network

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

Paris-Sud XI, Université de

9

Multiple Transmission Pathways and Disease Dynamics inaWaterborne Pathogen Model  

Microsoft Academic Search

Multiple transmission pathways exist for many waterborne diseases, including cholera, Giardia, Cryptosporidium, and Campylobacter. Theoretical work exploring the effects of multiple transmission pathways on disease dynamics is incomplete. Here, we consider\\u000a a simple ODE model that extends the classical SIR framework by adding a compartment(W) that tracks pathogen concentration in the water. Infected individuals shed pathogen into the water compartment,

Joseph H. Tien; David J. D. Earn

2010-01-01

10

Polyprenyl-dependent glycan assembly pathways in microbial pathogens  

E-print Network

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 ...

Hartley, Meredith Diane

2011-01-01

11

Review article Escherichia coli as a pathogen in dogs and cats  

E-print Network

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

Paris-Sud XI, Université de

12

Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion.  

PubMed

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

Dando, Samantha J; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J; St John, James A; Ekberg, Jenny A K; Batzloff, Michael; Ulett, Glen C; Beacham, Ifor R

2014-10-01

13

Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis  

Microsoft Academic Search

Furin is a secretory pathway endoprotease that catalyses the maturation of a strikingly diverse group of proprotein substrates, ranging from growth factors and receptors to pathogen proteins, in multiple compartments within the trans-Golgi network (TGN)\\/endosomal system. This review focuses on recent developments in the biochemistry and cell biology of the endoprotease, including the mechanism of TGN localization, phosphorylation-dependent regulation of

Sean S. Molloy; Eric D. Anderson; Franois Jean; Gary Thomas

1999-01-01

14

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

PubMed Central

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

2015-01-01

15

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

PubMed Central

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

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

2014-01-01

16

Video Article Assay for Pathogen-Associated Molecular Pattern (PAMP)-Triggered Immunity (PTI)  

E-print Network

Video Article Assay for Pathogen-Associated Molecular Pattern (PAMP)-Triggered Immunity (PTI or their activity, which leads to effector-triggered immunity (ETI)2. We describe a cell death-based assay for PTI induced by the first infiltration is able to delay or prevent the appearance of cell death due

Pawlowski, Wojtek

17

Pathogenic Role of the Wnt Signaling Pathway Activation In Laser-Induced Choroidal Neovascularization  

PubMed Central

Purpose. Choroidal neovascularization (CNV) is a severe complication of AMD. The Wnt signaling pathway has been shown to mediate angiogenesis. The purpose of this study was to investigate the pathogenic role of the Wnt pathway in CNV and explore the therapeutic potential of a novel Wnt signaling inhibitor in CNV. Methods. Adult rats and mice were photocoagulated using diode laser to induce CNV. On the same day, the animals were intravitreally injected with a monoclonal antibody (Mab2F1) blocking LRP6 or nonspecific mouse IgG. The Wnt signaling activation and target gene expression in the eyecup were determined by Western blot analysis. Fundus angiography was used to examine leakage from the laser lesion. CNV areas were measured on choroidal flatmount using FITC-dextran. Results. Levels of Wnt pathway components and Wnt target gene expression were elevated in both laser-induced CNV rat and mouse eyecups, suggesting activation of the Wnt pathway. Significant suppression of Wnt signaling was observed in the Mab2F1 treatment group. Mab2F1 decreased vascular leakage from CNV lesions and reduced the neovascular area in laser-induced CNV rats. Mab2F1 inhibited the hypoxia-induced activation of Wnt signaling in cultured RPE cells. Mab2F1 also ameliorated retinal inflammation and vascular leakage in the eyecups of very low-density lipoprotein receptor knockout mice, a model of subretinal neovascularization. Conclusions. The Wnt pathway is activated in the laser-induced CNV models and plays a pathogenic role in CNV. Blockade of Wnt signaling using an anti-LRP6 antibody has therapeutic potential in CNV. PMID:23211829

Hu, Yang; Chen, Ying; Lin, Mingkai; Lee, Kyungwon; Mott, Robert A.; Ma, Jian-xing

2013-01-01

18

Peroxisomal and Mitochondrial ?-Oxidation Pathways Influence the Virulence of the Pathogenic Fungus Cryptococcus neoformans  

PubMed Central

An understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungus Cryptococcus neoformans is important for developing antifungal therapies. Lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial ?-oxidation pathways to utilize this potential carbon source. In addition, lipids are important signaling molecules in both fungi and mammals. In this report, we demonstrate that defects in the peroxisomal and mitochondrial ?-oxidation pathways influence the growth of C. neoformans on fatty acids as well as the virulence of the fungus in a mouse inhalation model of cryptococcosis. Disease attenuation may be due to the cumulative influence of altered carbon source acquisition or processing, interference with secretion, changes in cell wall integrity, and an observed defect in capsule production for the peroxisomal mutant. Altered capsule elaboration in the context of a ?-oxidation defect was unexpected but is particularly important because this trait is a major virulence factor for C. neoformans. Additionally, analysis of mutants in the peroxisomal pathway revealed a growth-promoting activity for C. neoformans, and subsequent work identified oleic acid and biotin as candidates for such factors. Overall, this study reveals that ?-oxidation influences virulence in C. neoformans by multiple mechanisms that likely include contributions to carbon source acquisition and virulence factor elaboration. PMID:22707485

Kretschmer, Matthias; Wang, Joyce

2012-01-01

19

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

PubMed Central

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

2013-01-01

20

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

PubMed Central

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 (CC 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

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

2015-01-01

21

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

PubMed

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. 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25186463

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

2015-01-01

22

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease  

PubMed Central

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD. PMID:18625748

Bjrkqvist, Maria; Wild, Edward J.; Thiele, Jenny; Silvestroni, Aurelio; Andre, Ralph; Lahiri, Nayana; Raibon, Elsa; Lee, Richard V.; Benn, Caroline L.; Soulet, Denis; Magnusson, Anna; Woodman, Ben; Landles, Christian; Pouladi, Mahmoud A.; Hayden, Michael R.; Khalili-Shirazi, Azadeh; Lowdell, Mark W.; Brundin, Patrik; Bates, Gillian P.; Leavitt, Blair R.; Mller, Thomas; Tabrizi, Sarah J.

2008-01-01

23

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

PubMed Central

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

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

2014-01-01

24

Inhibitors of the sulfur assimilation pathway in bacterial pathogens as enhancers of antibiotic therapy.  

PubMed

The rising emergence of antibiotic resistance urges the search for new strategies to defeat microorganisms that lead to persistent infections of the host. Tolerant to antibiotics, slowly replicating bacteria often cause latent and persistent infections that are the most challenging for pharmacological treatment. Persistence inside the host requires an extensive re-programming of the pathogen metabolic functions, due to the extremely hostile environment they face. Therefore, targeting key metabolic functions could result in better antibiotic treatments, shortened latency periods, and increased susceptibility to traditional antibiotics. Bacteria, differently from mammals, assimilate inorganic sulfur into cysteine, the precursor of a number of key metabolites including reducing agents, cofactors and membrane components. Inhibition of cysteine biosynthesis was proven to interfere heavily with the ability of pathogens to fight oxidative stress, to infect the host and to establish long-term infections. This review has the purpose of i) briefly summarizing the key structural and functional properties of transporters and enzymes involved in sulfur assimilation, ii) presenting biological evidence that supports the exploitation of this pathway for the identification of potential targets and, iii) highlighting intense efforts and advancements in the search of promising candidates for the development of novel compounds that enhance antibiotics therapy. PMID:25388010

Campanini, Barbara; Pieroni, Marco; Raboni, Samanta; Bettati, Stefano; Benoni, Roberto; Pecchini, Chiara; Costantino, Gabriele; Mozzarelli, Andrea

2015-01-01

25

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  

Microsoft Academic Search

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

Jacques Fantini; Marc Maresca; Djilali Hammache; Nouara Yahi; Olivier Delzay

2000-01-01

26

RESEARCH ARTICLE Open Access Activation of pro-oncogenic pathways in  

E-print Network

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

Paris-Sud XI, Université de

27

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

PubMed Central

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

Kim, Charles C.; Falkow, Stanley

2004-01-01

28

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

PubMed

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

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

1998-07-01

29

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

Microsoft Academic Search

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

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

2002-01-01

30

The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum  

Microsoft Academic Search

Genetically accessible host models are useful for studying microbial pathogenesis because they offer the means to identify novel strategies that pathogens use to evade immune mechanisms, cause cellular injury, and induce disease. We have developed conditions under which the human pathogen Pseudomonas aeruginosa infects Dictyostelium discoideum, a genetically tractable eukaryotic organism. When D. discoideum is plated on nutrient agar plates

Stefan Pukatzki; Richard H. Kessin; John J. Mekalanos

2002-01-01

31

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

E-print Network

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

Holbrook, N. Michele

32

Toward a molecular pathogenic pathway for Yersinia pestis YopM  

PubMed Central

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 2448 h post-infection (p.i.). To identify potential direct effects of YopM in-vivo we tested for effects of YopM at 1 h and 1618 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

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

33

The Cpc1 regulator of the cross-pathway control of amino acid biosynthesis is required for pathogenicity of the vascular pathogen Verticillium longisporum.  

PubMed

The plant-pathogenic fungus Verticillium longisporum is a causal agent of early senescence and ripening in cruciferous crops like Brassica napus. Verticillium wilts have become serious agricultural threats in recent decades. Verticillium species infect host plants through the roots and colonize xylem vessels of the host plant. The xylem fluid provides an environment with limited carbon sources and unbalanced amino acid supply, which requires V. longisporum to induce the cross-pathway control of amino acid biosynthesis. RNA-mediated gene silencing reduced the expression of the two CPC1 isogenes (VlCPC1-1 and VlCPC1-2) of the allodiploid V. longisporum up to 85%. VlCPC1 encodes the conserved transcription factor of the cross-pathway control. The silenced mutants were highly sensitive to amino-acid starvation, and the infected plants showed significantly fewer symptoms such as stunting or early senescence in oilseed rape plant infection assays. Consistently, deletion of single CPC1 of the haploid V. dahliae resulted in strains that are sensitive to amino-acid starvation and cause strongly reduced symptoms in the plant-host tomato (Solanum lycopersicum). The allodiploid V. longisporum and the haploid V. dahliae are the first phytopathogenic fungi that were shown to require CPC1 for infection and colonization of their respective host plants, oilseed rape and tomato. PMID:23883358

Timpner, Christian; Braus-Stromeyer, Susanna A; Tran, Van Tuan; Braus, Gerhard H

2013-11-01

34

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

E-print Network

.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

Grünwald, Niklaus J.

35

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...

36

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

PubMed

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 4C for 48h. A total of 16,750 and 18,068 putative genes were annotated for 4C-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 4C treatment for 48h. 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

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

2014-12-01

37

Evolution of a pathogen: a comparative genomics analysis identifies a genetic pathway to pathogenesis in Acinetobacter.  

PubMed

Acinetobacter baumannii is an emergent and global nosocomial pathogen. In addition to A. baumannii, other Acinetobacter species, especially those in the Acinetobacter calcoaceticus-baumannii (Acb) complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in A. baumannii have been identified, the genetic mechanisms that explain the emergence of A. baumannii as the most widespread and virulent Acinetobacter species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus Acinetobacter. However, a global comparison of genomic features between Acinetobacter spp. has not been described in the literature. In this study, 136 Acinetobacter genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the Acinetobacter genus. A whole genome phylogeny confirmed that A. baumannii is a monophyletic clade and that the larger Acb complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR) analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of A. baumannii. In addition, several genes associated with A. baumannii pathogenesis were found to be more conserved in the Acb complex, and especially in A. baumannii, than in other Acinetobacter genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of A. baumannii. The identification of novel features associated with transcriptional regulation and acquired by clades in the Acb complex presents targets for better understanding the evolution of pathogenesis and virulence in the expansion of the genus. PMID:23365658

Sahl, Jason W; Gillece, John D; Schupp, James M; Waddell, Victor G; Driebe, Elizabeth M; Engelthaler, David M; Keim, Paul

2013-01-01

38

In Planta Biocontrol of Pectobacterium atrosepticum by Rhodococcus erythropolis Involves Silencing of Pathogen Communication by the Rhodococcal Gamma-Lactone Catabolic Pathway.  

PubMed

The virulence of numerous Gram-negative bacteria is under the control of a quorum sensing process based on synthesis and perception of N-acyl homoserine lactones. Rhodococcus erythropolis, a Gram-positive bacterium, has recently been proposed as a biocontrol agent for plant protection against soft-rot bacteria, including Pectobacterium. Here, we show that the ?-lactone catabolic pathway of R. erythropolis disrupts Pectobacterium communication and prevents plant soft-rot. We report the first characterization and demonstration of N-acyl homoserine lactone quenching in planta. In particular, we describe the transcription of the R. erythropolis lactonase gene, encoding the key enzyme of this pathway, and the subsequent lactone breakdown. The role of this catabolic pathway in biocontrol activity was confirmed by deletion of the lactonase gene from R. erythropolis and also its heterologous expression in Escherichia coli. The ?-lactone catabolic pathway is induced by pathogen communication rather than by pathogen invasion. This is thus a novel and unusual biocontrol pathway, differing from those previously described as protecting plants from phytopathogens. These findings also suggest the existence of an additional pathway contributing to plant protection. PMID:23805254

Barbey, Corinne; Crpin, Alexandre; Bergeau, Dorian; Ouchiha, Asma; Mijouin, Lily; Taupin, Laure; Orange, Nicole; Feuilloley, Marc; Dufour, Alain; Burini, Jean-Franois; Latour, Xavier

2013-01-01

39

In Planta Biocontrol of Pectobacterium atrosepticum by Rhodococcus erythropolis Involves Silencing of Pathogen Communication by the Rhodococcal Gamma-Lactone Catabolic Pathway  

PubMed Central

The virulence of numerous Gram-negative bacteria is under the control of a quorum sensing process based on synthesis and perception of N-acyl homoserine lactones. Rhodococcus erythropolis, a Gram-positive bacterium, has recently been proposed as a biocontrol agent for plant protection against soft-rot bacteria, including Pectobacterium. Here, we show that the ?-lactone catabolic pathway of R. erythropolis disrupts Pectobacterium communication and prevents plant soft-rot. We report the first characterization and demonstration of N-acyl homoserine lactone quenching in planta. In particular, we describe the transcription of the R. erythropolis lactonase gene, encoding the key enzyme of this pathway, and the subsequent lactone breakdown. The role of this catabolic pathway in biocontrol activity was confirmed by deletion of the lactonase gene from R. erythropolis and also its heterologous expression in Escherichia coli. The ?-lactone catabolic pathway is induced by pathogen communication rather than by pathogen invasion. This is thus a novel and unusual biocontrol pathway, differing from those previously described as protecting plants from phytopathogens. These findings also suggest the existence of an additional pathway contributing to plant protection. PMID:23805254

Barbey, Corinne; Crpin, Alexandre; Bergeau, Dorian; Ouchiha, Asma; Mijouin, Lily; Taupin, Laure; Orange, Nicole; Feuilloley, Marc; Dufour, Alain; Burini, Jean-Franois; Latour, Xavier

2013-01-01

40

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

PubMed

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

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

2009-09-01

41

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

PubMed

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

Kaplan, Allen P; Joseph, Kusumam

2014-01-01

42

Molecular Plant Volume 1 Number 3 Pages 423445 May 2008 RESEARCH ARTICLE Activation of Defense Response Pathways by OGs  

E-print Network

, or the bacterial flagellin peptide Flg22, general elicitors of the basal defense response in plants. AlthoughMolecular Plant · Volume 1 · Number 3 · Pages 423­445 · May 2008 RESEARCH ARTICLE Activation of Defense Response Pathways by OGs and Flg22 Elicitors in Arabidopsis Seedlings Carine Denouxa,b , Roberta

Ausubel, Frederick M.

43

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

E-print Network

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, ...

Morrison, Michael James

2014-01-01

44

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

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

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

2014-01-01

45

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

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

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

2014-01-01

46

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

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

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

2014-01-01

47

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

PubMed

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

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

2015-01-01

48

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

Microsoft Academic Search

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

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

2001-01-01

49

Cyclo(Phe-Pro) Produced by the Human Pathogen Vibrio vulnificus Inhibits Host Innate Immune Responses through the NF-?B Pathway.  

PubMed

Cyclo(Phe-Pro) (cFP) is a secondary metabolite produced by certain bacteria and fungi. Although recent studies highlight the role of cFP in cell-to-cell communication by bacteria, its role in the context of the host immune response is poorly understood. In this study, we investigated the role of cFP produced by the human pathogen Vibrio vulnificus in the modulation of innate immune responses toward the pathogen. cFP suppressed the production of proinflammatory cytokines, nitric oxide, and reactive oxygen species in a lipopolysaccharide (LPS)-stimulated monocyte/macrophage cell line and in bone marrow-derived macrophages. Specifically, cFP inhibited inhibitory ?B (I?B) kinase (IKK) phosphorylation, I?B? degradation, and nuclear factor ?B (NF-?B) translocation to the cell nucleus, indicating that cFP affects the NF-?B pathway. We searched for genes that are responsible for cFP production in V. vulnificus and identified VVMO6_03017 as a causative gene. A deletion of VVMO6_03017 diminished cFP production and decreased virulence in subcutaneously inoculated mice. In summary, cFP produced by V. vulnificus actively suppresses the innate immune responses of the host, thereby facilitating its survival and propagation in the host environment. PMID:25561711

Kim, Kiwan; Kim, Na-Jeong; Kim, So Young; Kim, In Hwang; Kim, Kun-Soo; Lee, Gap Ryol

2015-03-01

50

High-Content Image-Based Screening of a Signal Transduction Pathway Inhibitor Small-Molecule Library against Highly Pathogenic RNA Viruses.  

PubMed

High-content image-based screening was developed as an approach to test a small-molecule library of compounds targeting signal transduction pathways for antiviral activity against multiple highly pathogenic RNA viruses. Of the 2843 compounds screened, 120 compounds exhibited ?60% antiviral activity. Four compounds (E225-0969, E528-0039, G118-0778, and G544-0735), which were most active against Rift Valley fever virus (RVFV) and showed broad-spectrum antiviral activity, were selected for further evaluation for their concentration-response profile and cytotoxicity. These compounds did not show any visible cytotoxicity at the highest concentration of compound tested (200 M). All four of these compounds were more active than ribavirin against several viruses. One compound, E225-0969, had the lowest effective concentration (EC50 = 1.9-8.92 M) for all the viruses tested. This compound was 13- and 43-fold more inhibitory against RVFV and Chikungunya virus (CHIKV), respectively, than ribavirin. The highest selectivity index (>106.2) was for E225-0969 against CHIKV. Time-of-addition assays suggested that all four lead compounds targeted early steps in the viral life cycle (entry and/or replication) but not virus egress. Overall, this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals against highly pathogenic viruses. PMID:25342145

Mudhasani, Rajini; Kota, Krishna P; Retterer, Cary; Tran, Julie P; Tritsch, Sarah R; Zamani, Rouzbeh; Whitehouse, Chris A; Bavari, Sina

2015-01-01

51

Pathogen Sensing Pathways in Human Embryonic Stem Cell Derived-Endothelial Cells: Role of NOD1 Receptors  

PubMed Central

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

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

52

MICROBIOLOGY: A Bacterial Pathogen Sees the Light  

NSDL National Science Digital Library

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.

John T. M. Kennis (Faculty of Sciences, Vrije Universiteit;Biophysics Department); Sean Crosson (The University of Chicago;Department of Biochemistry and Molecular Biology)

2007-08-24

53

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease  

PubMed Central

Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha 33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin- inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated. PMID:2007860

1991-01-01

54

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.

55

Identification and Regulation of the N-Acetylglucosamine Utilization Pathway of the Plant Pathogenic Bacterium Xanthomonas campestris pv. campestris ?  

PubMed Central

Xanthomonas campestris pv. campestris, the causal agent of black rot disease of brassicas, is known for its ability to catabolize a wide range of plant compounds. This ability is correlated with the presence of specific carbohydrate utilization loci containing TonB-dependent transporters (CUT loci) devoted to scavenging specific carbohydrates. In this study, we demonstrate that there is an X. campestris pv. campestris CUT system involved in the import and catabolism of N-acetylglucosamine (GlcNAc). Expression of genes belonging to this GlcNAc CUT system is under the control of GlcNAc via the LacI family NagR and GntR family NagQ regulators. Analysis of the NagR and NagQ regulons confirmed that GlcNAc utilization involves NagA and NagB-II enzymes responsible for the conversion of GlcNAc-6-phosphate to fructose-6-phosphate. Mutants with mutations in the corresponding genes are sensitive to GlcNAc, as previously reported for Escherichia coli. This GlcNAc sensitivity and analysis of the NagQ and NagR regulons were used to dissect the X. campestris pv. campestris GlcNAc utilization pathway. This analysis revealed specific features, including the fact that uptake of GlcNAc through the inner membrane occurs via a major facilitator superfamily transporter and the fact that this amino sugar is phosphorylated by two proteins belonging to the glucokinase family, NagK-IIA and NagK-IIB. However, NagK-IIA seems to play a more important role in GlcNAc utilization than NagK-IIB under our experimental conditions. The X. campestris pv. campestris GlcNAc NagR regulon includes four genes encoding TonB-dependent active transporters (TBDTs). However, the results of transport experiments suggest that GlcNAc passively diffuses through the bacterial envelope, an observation that calls into question whether GlcNAc is a natural substrate for these TBDTs and consequently is the source of GlcNAc for this nonchitinolytic plant-associated bacterium. PMID:20081036

Boulanger, Alice; Djean, Guillaume; Lautier, Martine; Glories, Marie; Zischek, Claudine; Arlat, Matthieu; Lauber, Emmanuelle

2010-01-01

56

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

PubMed

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

Christen, Danilo; Tharin, Manuel; Perrin-Cherioux, Sandrine; Abou-Mansour, Eliane; Tabacchi, Raphal; Dfago, Genevive

2005-09-01

57

Transcription of genes in the biosynthetic pathway for fumonisin mycotoxins is epigenetically and differentially regulated in the fungal maize pathogen Fusarium verticillioides.  

PubMed

When the fungal pathogen Gibberella moniliformis (anamorph, Fusarium verticillioides) colonizes maize and maize-based products, it produces class B fumonisin (FB) mycotoxins, which are a significant threat to human and animal health. FB biosynthetic enzymes and accessory proteins are encoded by a set of clustered and cotranscribed genes collectively named FUM, whose molecular regulation is beginning to be unraveled by researchers. FB accumulation correlates with the amount of transcripts from the key FUM genes, FUM1, FUM21, and FUM8. In fungi in general, gene expression is often partially controlled at the chromatin level in secondary metabolism; when this is the case, the deacetylation and acetylation (and other posttranslational modifications) of histones are usually crucial in the regulation of transcription. To assess whether epigenetic factors regulate the FB pathway, we monitored FB production and FUM1, FUM21, and FUM8 expression in the presence of a histone deacetylase inhibitor and verified by chromatin immunoprecipitation the relative degree of histone acetylation in the promoter regions of FUM1, FUM21, and FUM8 under FB-inducing and noninducing conditions. Moreover, we generated transgenic F. verticillioides strains expressing GFP under the control of the FUM1 promoter to determine whether its strength under FB-inducing and noninducing conditions was influenced by its location in the genome. Our results indicate a clear and differential role for chromatin remodeling in the regulation of FUM genes. This epigenetic regulation can be attained through the modulation of histone acetylation at the level of the promoter regions of the key biosynthetic genes FUM1 and FUM21, but less so for FUM8. PMID:22117026

Visentin, I; Montis, V; Dll, K; Alabouvette, C; Tamietti, G; Karlovsky, P; Cardinale, F

2012-03-01

58

The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR)  

PubMed Central

The filamentous fungal pathogen Aspergillus fumigatus secretes hydrolytic enzymes to acquire nutrients from host tissues. The production of these enzymes exerts stress on the endoplasmic reticulum (ER), which is alleviated by two stress responses: the unfolded protein response (UPR), which adjusts the protein folding capacity of the ER, and ER-associated degradation (ERAD), which disposes of proteins that fail to fold correctly. In this study, we examined the contribution of these integrated pathways to the growth and virulence of A. fumigatus, focusing on the ERAD protein DerA and the master regulator of the UPR, HAcA. A ?derA mutant grew normally and showed no increase in sensitivity to ER stress. However, expression of the UPR target gene bipA was constitutively elevated in this strain, suggesting that the UPR was compensating for the absence of DerA function. To test this, the UPR was disrupted by deleting the hacA gene. The combined loss of derA and hacA caused a more severe reduction in hyphal growth, antifungal drug resistance and protease secretion than the loss of either gene alone, suggesting that DerA and HacA cooperate to support these functions. Moreover, the ?derA/?hacA mutant was avirulent in a mouse model of invasive aspergillosis, which contrasted the wild-type virulence of ?derA and the reduced virulence of the ?hacA mutant. Taken together, these data demonstrate that DerA cooperates with the UPR to support the expression of virulence-related attributes of A. fumigatus. PMID:21217201

Richie, Daryl L; Feng, Xizhi; Hartl, Lukas; Aimanianda, Vishukumar; Krishnan, Karthik; Powers-Fletcher, Margaret V; Watson, Douglas S; Galande, Amit K; White, Stephanie M; Willett, Taryn; Latg, Jean-Paul; Rhodes, Judith C

2011-01-01

59

The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR).  

PubMed

The filamentous fungal pathogen Aspergillus fumigatus secretes hydrolytic enzymes to acquire nutrients from host tissues. The production of these enzymes exerts stress on the endoplasmic reticulum (ER), which is alleviated by two stress responses: the unfolded protein response (UPR), which adjusts the protein folding capacity of the ER, and ER-associated degradation (ERAD), which disposes of proteins that fail to fold correctly. In this study, we examined the contribution of these integrated pathways to the growth and virulence of A. fumigatus, focusing on the ERAD protein DerA and the master regulator of the UPR, HacA. A ?derA mutant grew normally and showed no increase in sensitivity to ER stress. However, expression of the UPR target gene bipA was constitutively elevated in this strain, suggesting that the UPR was compensating for the absence of DerA function. To test this, the UPR was disrupted by deleting the hacA gene. The combined loss of derA and hacA caused a more severe reduction in hyphal growth, antifungal drug resistance and protease secretion than the loss of either gene alone, suggesting that DerA and HacA cooperate to support these functions. Moreover, the ?derA/?hacA mutant was avirulent in a mouse model of invasive aspergillosis, which contrasted the wild type virulence of ?derA and the reduced virulence of the ?hacA mutant. Taken together, these data demonstrate that DerA cooperates with the UPR to support the expression of virulence-related attributes of A. fumigatus. PMID:21217201

Richie, Daryl L; Feng, Xizhi; Hartl, Lukas; Aimanianda, Vishukumar; Krishnan, Karthik; Powers-Fletcher, Margaret V; Watson, Douglas S; Galande, Amit K; White, Stephanie M; Willett, Taryn; Latg, Jean-Paul; Rhodes, Judith C; Askew, David S

2011-01-01

60

A Ligand-Receptor Mechanism in Plant-Pathogen Recognition  

NSDL National Science Digital Library

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.

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

1996-12-20

61

Review Article Nomenclature, Molecular Genetics and Clinical Significance of the Precursor Lesions in the Serrated Polyp Pathway of Colorectal Carcinoma  

Microsoft Academic Search

Serrated adenomas (SAs) are part of the distinct serrated polyp pathway of colorectal carcinogenesis characterized by microsatellite instability and deficiency in DNA mismatch repair. Sessile SA is a recently recognized lesion that typically presents as a large sessile polyp, but lacks the conventional dysplasia. It is more frequently found on the right side than on the left side of the

John J. Liang; Sadir Alrawi; Dongfeng Tan

62

A novel quantitative mating assay for the fungal pathogen Cryptococcus neoformans provides insight into signalling pathways responding to nutrients and temperature  

Microsoft Academic Search

Cryptococcus neoformans is a fungal pathogen that causes a lethal meningitis in immunocompromised individuals. Several factors are associated with virulence of this fungus, including its mating type; however, the mechanism by which mating type affects virulence is unknown. C. neoformans is a basidiomycete that exists in two mating types called a and a that can fuse to form an ala

Hui Dong; William Courchesne

1998-01-01

63

Signaling During Pathogen Infection  

NSDL National Science Digital Library

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.

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

2006-05-16

64

The Endless Race Between Plant and Pathogen  

NSDL National Science Digital Library

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.

Pamela Hines (AAAS;); Jean Marx (AAAS;)

2001-06-22

65

Original Article Gene Expression Profiling Reveals a Diverse Array of Pathways Inhibited by Nuclear Receptor SHP during Adipogenesis  

Microsoft Academic Search

Orphan receptor small heterodimer partner (SHP, NROB2) has been shown to be a metabolic regulator in pathways associated with several major aspects of the metabolic syndrome. However, the significance and transcriptional regulatory role of SHP in adipocyte differentiation remain unclear. Transcriptional profiles of 3T3-L1 preadipocytes and early differentiating preadipocytes in response to SHP were systemically surveyed using Affymetrix Genome Array

Guisheng Song; Kyungtae Park; Li Wang

66

The Alternative Pathway is critical for Pathogenic Complement Activation in Endotoxin- and Diet-induced Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice  

PubMed Central

Background The early components of the classical and lectin complement pathways have been shown to protect low-density lipoprotein receptor deficient mice (Ldlr?/?) from early atherogenesis. However, the role of the alternative pathway remained unknown and that was investigated in this study. Methods and Results Mice lacking factor B (Bf?/?), the initiator of the alternative pathway, were crossed with Ldlr?/? mice and studied under different pro-atherogenic conditions. There was no statistically significant difference in lipid profiles or atherosclerotic lesion development between Bf?/?.Ldlr?/? and Ldlr?/? mice fed a low-fat diet. However, in these groups administration of bacterial lipopolysaccharide (LPS) led to a significant increase in atherosclerosis only in Ldlr?/? and not in Bf?/?.Ldlr?/? mice, indicating that the alternative pathway is necessary for endotoxin-mediated atherogenesis. Bf?/?.Ldlr?/? mice also had significantly decreased cross-sectional aortic root lesion fraction area and reduced lesion complexity compared to Ldlr?/? animals after a 12-week period of high-fat diet, although this was also accompanied by reduced levels of serum cholesterol. Under both experimental conditions, the atherosclerotic changes in the Bf?/?.Ldlr?/? mice were accompanied by a marked reduction in complement activation in the circulation and in atherosclerotic plaques, with no statistical significant differences in IgG deposition or in the serum antibody response to oxidised LDL. Conclusions These data demonstrate that amplification of complement activation by the alternative pathway in response to LPS or high fat diet plays a pro-atherogenic role. PMID:20974996

Malik, Talat H.; Cortini, Andrea; Carassiti, Daniele; Boyle, Joseph J; Haskard, Dorian O.; Botto, Marina

2010-01-01

67

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

Microsoft Academic Search

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

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

2012-01-01

68

Mechanisms of pathogen entry through the endosomal compartments  

Microsoft Academic Search

Several pathogens bacteria, viruses and parasites must enter mammalian cells for survival, replication and immune-system evasion. These pathogens generally make use of existing cellular pathways that are designed for nutrient uptake, receptor downregulation and signalling. Because most of these pathways end in lysosomes, an organelle that is capable of killing microorganisms, pathogens have developed remarkable means to avoidinteractions

Jean Gruenberg; F. Gisou van der Goot

2006-01-01

69

Age-related resistance of Nicotiana benthamiana against hemibiotrophic pathogen Phytophthora infestans requires both ethylene- and salicylic acid-mediated signaling pathways.  

PubMed

Phytophthora infestans, the agent of late blight disease of potato, is a hemibiotrophic pathogen with biotrophic action during early infection and necrotrophic in the later stage of colonization. Mature Nicotiana benthamiana was resistant to P. infestans, whereas relatively young plants were susceptible to this pathogen. Young plants became resistant following a pretreatment with acibenzolar-S-methyl, a functional analog of salicylic acid (SA), indicating that susceptibility of young plants is due to a lack of induction of SA signaling. Further analysis with virus-induced gene silencing indicated that NbICS1 and NbEIN2, the genes for SA biosynthesis and ethylene (ET) signaling, respectively, are required for the resistance of mature N. benthamiana against P. infestans. Furthermore, these genes are required for the production of reactive oxygen species (ROS) induced by treatment of the INF1 elicitor. In NbICS1-silenced plants, cell death induced by either INF1 or necrosis-inducing protein NPP1.1 was significantly accelerated. Expression of genes for phytoalexin (capsidiol) biosynthesis, NbEAS and NbEAH, were regulated by ET, and gene silencing of either of them compromised resistance of N. benthamiana to P. infestans. Together, these results suggest that resistance of N. benthamiana against hemibiotrophic P. infestans requires both SA-regulated appropriate induction of cell death and ET-induced production of phytoalexin. PMID:20687803

Shibata, Yusuke; Kawakita, Kazuhito; Takemoto, Daigo

2010-09-01

70

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

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

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

2012-01-01

71

The periodontal pathogen Porphyromonas gingivalis changes the gene expression in vascular smooth muscle cells involving the TGFbeta/Notch signalling pathway and increased cell proliferation  

PubMed Central

Background Porphyromonas gingivalis is a gram-negative bacterium that causes destructive chronic periodontitis. In addition, this bacterium is also involved in the development of cardiovascular disease. The aim of this study was to investigate the effects of P. gingivalis infection on gene and protein expression in human aortic smooth muscle cells (AoSMCs) and its relation to cellular function. Results AoSMCs were exposed to viable P. gingivalis for 24?h, whereafter confocal fluorescence microscopy was used to study P. gingivalis invasion of AoSMCs. AoSMCs proliferation was evaluated by neutral red assay. Human genome microarray, western blot and ELISA were used to investigate how P. gingivalis changes the gene and protein expression of AoSMCs. We found that viable P. gingivalis invades AoSMCs, disrupts stress fiber structures and significantly increases cell proliferation. Microarray results showed that, a total of 982 genes were identified as differentially expressed with the threshold log2 fold change?>?|1| (adjust p-value <0.05). Using bioinformatic data mining, we demonstrated that up-regulated genes are enriched in gene ontology function of positive control of cell proliferation and down-regulated genes are enriched in the function of negative control of cell proliferation. The results from pathway analysis revealed that all the genes belonging to these two categories induced by P. gingivalis were enriched in 25 pathways, including genes of Notch and TGF-beta pathways. Conclusions This study demonstrates that P. gingivalis is able to invade AoSMCs and stimulate their proliferation. The activation of TGF-beta and Notch signaling pathways may be involved in the bacteria-mediated proliferation of AoSMCs. These findings further support the association between periodontitis and cardiovascular diseases. PMID:24209892

2013-01-01

72

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

PubMed

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

Laffont, Carole; Rey, Thomas; Andr, Olivier; Novero, Mara; Kazmierczak, Thophile; Debell, Frdric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

2015-01-01

73

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

PubMed Central

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

Laffont, Carole; Rey, Thomas; Andr, Olivier; Novero, Mara; Kazmierczak, Thophile; Debell, Frdric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

2015-01-01

74

Unraveling the Novel Structure and Biosynthetic Pathway of O-Linked Glycans in the Golgi Apparatus of the Human Pathogenic Yeast Cryptococcus neoformans.  

PubMed

Cryptococcus neoformans is an encapsulated basidiomycete causing cryptococcosis in immunocompromised humans. The cell surface mannoproteins of C. neoformans were reported to stimulate the host T-cell response and to be involved in fungal pathogenicity; however, their O-glycan structure is uncharacterized. In this study, we performed a detailed structural analysis of the O-glycans attached to cryptococcal mannoproteins using HPLC combined with exoglycosidase treatment and showed that the major C. neoformans O-glycans were short manno-oligosaccharides that were connected mostly by ?1,2-linkages but connected by an ?1,6-linkage at the third mannose residue. Comparison of the O-glycan profiles from wild-type and uxs1? mutant strains strongly supports the presence of minor O-glycans carrying a xylose residue. Further analyses of C. neoformans mutant strains identified three mannosyltransferase genes involved in O-glycan extensions in the Golgi. C. neoformans KTR3, the only homolog of the Saccharomyces cerevisiae KRE2/MNT1 family genes, was shown to encode an ?1,2-mannosyltransferase responsible for the addition of the second mannose residue via an ?1,2-linkage to the major O-glycans. C. neoformans HOC1 and HOC3, homologs of the Saccharomyces cerevisiae OCH1 family genes, were shown to encode ?1,6-mannosyltransferases that can transfer the third mannose residue, via an ?1,6-linkage, to minor O-glycans containing xylose and to major O-glycans without xylose, respectively. Moreover, the C. neoformans ktr3? mutant strain, which displayed increased sensitivity to SDS, high salt, and high temperature, showed attenuated virulence in a mouse model of cryptococcosis, suggesting that the extended structure of O-glycans is required for cell integrity and full pathogenicity of C. neoformans. PMID:25477510

Lee, Dong-Jik; Bahn, Yong-Sun; Kim, Hong-Jin; Chung, Seung-Yeon; Kang, Hyun Ah

2015-01-16

75

Signal Pathway in Salt-Activated Expression of the Salmonella Pathogenicity Island 1 Type III Secretion System in Salmonella enterica Serovar Typhimurium ?  

PubMed Central

Salmonella enterica serovar Typhimurium secretes virulence factors for invasion called Sip proteins or Sips into its hosts through a type III secretion system (T3SS). In the absence of a host, S. enterica induces Sip secretion in response to sucrose or simple salts, such as NaCl. We analyzed induction of host-independent Sip secretion by monitoring protein secretion by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), assembly of needle complexes by electron microscopy, and transcription of virulence regulatory genes by quantitative reverse transcriptase PCR (real-time PCR). SDS-PAGE showed that addition of sucrose or simple salts, such as NaCl, to the growth medium induced Sip secretion without altering flagellar protein secretion, which requires a distinct T3SS. Electron microscopy confirmed that the amount of secreted Sips increased as the number of assembled needle complexes increased. Real-time PCR revealed that added sucrose or NaCl enhanced transcription of hilA, hilC, and hilD, which encode known regulators of Salmonella virulence. However, epistasis analysis implicated HilD and HilA, but not HilC, in the direct pathway from the salt stimulus to the Sip secretion response. Further analyses showed that the BarA/SirA two-component signal transduction pathway, but not the two-component sensor kinase EnvZ, directly activated hilD and hilA transcription and thus Sip secretion in response to either sucrose or NaCl. Finally, real-time PCR showed that salt does not influence transcription of the BarA/SirA-dependent csrB and csrC genes. A model is proposed for the major pathway in which sucrose or salt signals to enhance virulence gene expression. PMID:18441068

Mizusaki, Hideaki; Takaya, Akiko; Yamamoto, Tomoko; Aizawa, Shin-Ichi

2008-01-01

76

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

PubMed Central

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

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

2014-01-01

77

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

PubMed Central

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

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

2006-01-01

78

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

PubMed Central

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

Neres, Joo; 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

79

A Luman/CREB3ADP-ribosylation factor 4 (ARF4) signaling pathway mediates the response to Golgi stress and susceptibility to pathogens  

PubMed Central

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 CREB3ARF4 signaling cascade that may be part of a Golgi stress response set in motion by stimuli compromising Golgi capacity. PMID:24185178

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

80

Subversion of Cell Signaling by Pathogens  

PubMed Central

SUMMARY Pathogens exploit several eukaryotic signaling pathways during an infection. They have evolved specific effectors and toxins to hijack host cell machinery for their own benefit. Signaling molecules are preferentially targeted by pathogens because they globally regulate many cellular processes. Both viruses and bacteria manipulate and control pathways that regulate host cell survival and shape, including MAPK signaling, G-protein signaling, signals controlling cytoskeletal dynamics, and innate immune responses. PMID:22952390

Alto, Neal M.; Orth, Kim

2012-01-01

81

Pathogen intelligence  

PubMed Central

Different species inhabit different sensory worlds and thus have evolved diverse means of processing information, learning and memory. In the escalated arms race with host defense, each pathogenic bacterium not only has evolved its individual cellular sensing and behavior, but also collective sensing, interbacterial communication, distributed information processing, joint decision making, dissociative behavior, and the phenotypic and genotypic heterogeneity necessary for epidemiologic success. Moreover, pathogenic populations take advantage of dormancy strategies and rapid evolutionary speed, which allow them to save co-generated intelligent traits in a collective genomic memory. This review discusses how these mechanisms add further levels of complexity to bacterial pathogenicity and transmission, and how mining for these mechanisms could help to develop new anti-infective strategies. PMID:24551600

Steinert, Michael

2014-01-01

82

Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study  

PubMed Central

Background Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay. Methods In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t therapy. Results Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogen-breath-test-positivity was associated inversely with Helicobacter-positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05). In 38 patients (untreated (17) or on stable long-t IP-medication), the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s-1, 89 (2, 177) Nm.10-3, per 100 cells.?l-1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). T-helper count was inversely associated with flexor-rigidity before (p=0.01) and after adjustment for natural-killer count (-36(-63, -10) Nm.10-3 per 100 cells.?l-1, p=0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effect-sizes were independent of IP-medication, and not masked by including 13 patients receiving levodopa (except natural-killer count on flexor-rigidity). Cellular associations held after allowing for potentially confounding effect of hydrogen-breath-test or Helicobacter status. Moreover, additional reduction in stride and speed (68 (24, 112) mm & 103 (38, 168) mm.s-1, each p=0.002) was seen with Helicobacter-positivity. Hydrogen-breath-test-positivity, itself, was associated with higher natural-killer and T-helper counts, lower neutrophils (p=0.005, 0.02 & 0.008). Conclusion We propose a rigidity-associated subordinate pathway, flagged by a higher natural-killer count, tempered by a higher T-helper, against which Helicobacter protects by keeping SIBO at bay. PMID:23083400

2012-01-01

83

SEWAGE SLUDGE PATHOGEN TRANSPORT MODEL PROJECT  

EPA Science Inventory

The sewage sludge pathogen transport model predicts the number of Salmonella, Ascaris, and polioviruses which might be expected to occur at various points in the environment along 13 defined pathways. These pathways describe the use of dried or liquid, raw or anaerobically digest...

84

Bacterial itaconate degradation promotes pathogenicity.  

PubMed

Itaconate (methylenesuccinate) was recently identified as a mammalian metabolite whose production is substantially induced during macrophage activation. This compound is a potent inhibitor of isocitrate lyase, a key enzyme of the glyoxylate cycle, which is a pathway required for the survival of many pathogens inside the eukaryotic host. Here we show that numerous bacteria, notably many pathogens such as Yersinia pestis and Pseudomonas aeruginosa, have three genes for itaconate degradation. They encode itaconate coenzyme A (CoA) transferase, itaconyl-CoA hydratase and (S)-citramalyl-CoA lyase, formerly referred to as CitE-like protein. These genes are known to be crucial for survival of some pathogens in macrophages. The corresponding enzymes convert itaconate into the cellular building blocks pyruvate and acetyl-CoA, thus enabling the bacteria to metabolize itaconate and survive in macrophages. The itaconate degradation and detoxification pathways of Yersinia and Pseudomonas are the result of convergent evolution. This work revealed a common persistence factor operating in many pathogenic bacteria. PMID:24657929

Sasikaran, Jahminy; Ziemski, Micha?; Zadora, Piotr K; Fleig, Angela; Berg, Ivan A

2014-05-01

85

Protein signaling via type III secretion pathways in phytopathogenic bacteria  

E-print Network

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

Mudgettt, Mary Beth

86

Research article Variation in the response of Mimulus guttatus  

E-print Network

' or interference among signaling pathways associated with induced resistance (IR) to insects and systemic acquired resistance (SAR) to pathogens has produced exciting results and has generated widespread interest

Behmer, Spencer T.

87

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

PubMed

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

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

2014-03-01

88

MAIT cells and pathogen defense.  

PubMed

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

Cowley, Siobhn C

2014-12-01

89

Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!  

Microsoft Academic Search

Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing\\/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of

Nargis Khan; Uthaman Gowthaman; Susanta Pahari; Javed N. Agrewala

2012-01-01

90

Inflammatory pathways in spondyloarthritis.  

PubMed

Spondyloarthritis is the second most common form of chronic inflammatory arthritis and a unique hallmark of the disease is pathologic new bone formation. Several cytokine pathways have been genetically associated with ankylosing spondylitis (AS), the prototypic subtype of SpA, and additional evidence from human and animal studies support a role of these pathways in the disease. TNF has a key role in SpA as blockade significantly reduces inflammation and destruction, however the treatment does not halt new bone formation. New insights into the TNF pathway were recently obtained from an animal model specifically overexpressing the transmembrane form of TNF. This model leads to axial and peripheral new bone formation which is not seen in soluble TNF overexpression models, indicating different pathogenic roles of soluble and transmembrane TNF in arthritis development. Besides TNF, the IL-23/IL-17 axis is emerging as an important inflammatory pathway in SpA, as a SNP in the IL-23R locus has been associated with developing AS, mice overexpressing IL-23 develop SpA-like features and IL-17 blockade has been shown to be efficacious for AS patients in a phase II trial. In this review, we focus on the cytokine pathways that have recently been genetically associated with SpA, i.e. TNF, IL-1, IL-6 and IL-23/IL-17. We review the current genetic, experimental and human in vivo data available and discuss how these different pathways are involved in the pathophysiology of SpA. Additionally, we discuss how these pathways relate to the pathogenic new bone formation in SpA. PMID:23969080

Hreggvidsdottir, Hulda S; Noordenbos, Troy; Baeten, Dominique L

2014-01-01

91

Manipulation of costimulatory molecules by intracellular pathogens: veni, vidi, vici!!  

PubMed

Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. Costimulatory molecules expressed on the surface of various cells play a decisive role in the initiation and sustenance of immunity. Exploitation of the "code of conduct" of costimulation pathways provides evolutionary incentive to the pathogens and thereby abates the functioning of the immune system. Here we review how Mtb, HIV, Leishmania sp., and other pathogens manipulate costimulatory molecules to establish chronic infection. Impairment by pathogens in the signaling events delivered by costimulatory molecules may be responsible for defective T-cell responses; consequently organisms grow unhindered in the host cells. This review summarizes the convergent devices that pathogens employ to tune and tame the immune system using costimulatory molecules. Studying host-pathogen interaction in context with costimulatory signals may unveil the molecular mechanism that will help in understanding the survival/death of the pathogens. We emphasize that the very same pathways can potentially be exploited to develop immunotherapeutic strategies to eliminate intracellular pathogens. PMID:22719245

Khan, Nargis; Gowthaman, Uthaman; Pahari, Susanta; Agrewala, Javed N

2012-01-01

92

Fungal Pathogens: Survival and Replication within Macrophages.  

PubMed

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

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

2014-11-10

93

Molecular Pathways: The Hedgehog Signaling Pathway in Cancer  

PubMed Central

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

McMillan, Ross; Matsui, William

2012-01-01

94

Pathways for Cytokine Secretion  

NSDL National Science Digital Library

Cytokine secretion is a widely studied process, although little is known regarding the specific mechanisms that regulate cytokine release. Recent findings have shed light on some of the precise molecular pathways that regulate the packaging of newly synthesized cytokines from immune cells. These findings begin to elucidate pathways and mechanisms that underpin cytokine release in all cells. In this article, we review the highlights of some of these novel discoveries.

Amanda Stanley (Institute for Molecular Bioscience)

2010-08-01

95

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...

96

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

PubMed Central

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

Chan, Ho Yin Edwin

2014-01-01

97

Modulation of NF-?B signalling by microbial pathogens  

PubMed Central

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

Rahman, Masmudur M.; McFadden, Grant

2013-01-01

98

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

PubMed Central

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

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

99

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

PubMed

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

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

100

Taxonomy of bacterial fish pathogens  

PubMed Central

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

2011-01-01

101

CELL SIGNALING: Mitochondrial Longevity Pathways  

NSDL National Science Digital Library

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.

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

2007-02-02

102

Coevolution of Plants and Their Pathogens in Natural Habitats  

NSDL National Science Digital Library

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.

Jeremy J. Burdon (Commonwealth Scientific and Industrial Research Organization (CSIRO)âPlant Industry;); Peter H. Thrall (Commonwealth Scientific and Industrial Research Organization (CSIRO)âPlant Industry;)

2009-05-08

103

Parallel independent evolution of pathogenicity within the genus Yersinia  

PubMed Central

The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens. PMID:24753568

Reuter, Sandra; Connor, Thomas R.; Barquist, Lars; Walker, Danielle; Feltwell, Theresa; Harris, Simon R.; Fookes, Maria; Hall, Miquette E.; Petty, Nicola K.; Fuchs, Thilo M.; Corander, Jukka; Dufour, Muriel; Ringwood, Tamara; Savin, Cyril; Bouchier, Christiane; Martin, Liliane; Miettinen, Minna; Shubin, Mikhail; Riehm, Julia M.; Laukkanen-Ninios, Riikka; Sihvonen, Leila M.; Siitonen, Anja; Skurnik, Mikael; Falco, Juliana Pfrimer; Fukushima, Hiroshi; Scholz, Holger C.; Prentice, Michael B.; Wren, Brendan W.; Parkhill, Julian; Carniel, Elisabeth; Achtman, Mark; McNally, Alan; Thomson, Nicholas R.

2014-01-01

104

Pathogenic Microorganisms in Water  

NSDL National Science Digital Library

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.

Melissa Lenczewski

105

Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis  

Microsoft Academic Search

The emergence of multidrug resistant varieties of Mycobacterium tuberculosis has led to a search for novel drug targets. We have performed an insilico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen M. tuberculosis. Enzymes from the biochemical pathways of M. tuberculosis from the KEGG metabolic pathway database were compared with proteins from the hostH. sapiens,

Sharmila Anishetty; Mrudula Pulimi; Pennathur Gautam

2005-01-01

106

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...

107

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

PubMed Central

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

Watts, J L; Yancey, R J

1994-01-01

108

Pathogenic mechanisms in centronuclear myopathies.  

PubMed

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

Jungbluth, Heinz; Gautel, Mathias

2014-01-01

109

Pathogenic Mechanisms in Centronuclear Myopathies  

PubMed Central

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 excitationcontraction 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

Jungbluth, Heinz; Gautel, Mathias

2014-01-01

110

Review article Chemical architecture of antennal pathways  

E-print Network

proboscis extension in response to antennal sugar water stimulation and also associative learning component of feeding behaviour that is elicited by touching one antenna with a droplet of sugar water. By pairing an ini- tially neutral odour (conditioned stimulus) with the application of sugar water (uncon

Boyer, Edmond

111

Global Expression Studies of Yersinia Pestis Pathogenicity  

SciTech Connect

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.

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

2002-10-15

112

Latent Tuberculosis: Models, Computational Efforts and the Pathogens Regulatory Mechanisms during Dormancy  

PubMed Central

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

Magombedze, Gesham; Dowdy, David; Mulder, Nicola

2013-01-01

113

RAB11-mediated trafficking in host-pathogen interactions.  

PubMed

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

Guichard, Annabel; Nizet, Victor; Bier, Ethan

2014-09-01

114

Microbial risk assessment in heterogeneous aquifers: 1. Pathogen transport  

NASA Astrophysics Data System (ADS)

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.

Molin, S.; Cvetkovic, V.

2010-05-01

115

Microarrays for Pathogen Detection and Analysis  

PubMed Central

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

2011-01-01

116

A Network Approach to Predict Pathogenic Genes for Fusarium graminearum  

PubMed Central

Fusarium graminearum is the pathogenic agent of Fusarium head blight (FHB), which is a destructive disease on wheat and barley, thereby causing huge economic loss and health problems to human by contaminating foods. Identifying pathogenic genes can shed light on pathogenesis underlying the interaction between F. graminearum and its plant host. However, it is difficult to detect pathogenic genes for this destructive pathogen by time-consuming and expensive molecular biological experiments in lab. On the other hand, computational methods provide an alternative way to solve this problem. Since pathogenesis is a complicated procedure that involves complex regulations and interactions, the molecular interaction network of F. graminearum can give clues to potential pathogenic genes. Furthermore, the gene expression data of F. graminearum before and after its invasion into plant host can also provide useful information. In this paper, a novel systems biology approach is presented to predict pathogenic genes of F. graminearum based on molecular interaction network and gene expression data. With a small number of known pathogenic genes as seed genes, a subnetwork that consists of potential pathogenic genes is identified from the protein-protein interaction network (PPIN) of F. graminearum, where the genes in the subnetwork are further required to be differentially expressed before and after the invasion of the pathogenic fungus. Therefore, the candidate genes in the subnetwork are expected to be involved in the same biological processes as seed genes, which imply that they are potential pathogenic genes. The prediction results show that most of the pathogenic genes of F. graminearum are enriched in two important signal transduction pathways, including G protein coupled receptor pathway and MAPK signaling pathway, which are known related to pathogenesis in other fungi. In addition, several pathogenic genes predicted by our method are verified in other pathogenic fungi, which demonstrate the effectiveness of the proposed method. The results presented in this paper not only can provide guidelines for future experimental verification, but also shed light on the pathogenesis of the destructive fungus F. graminearum. PMID:20957229

Liu, Xiaoping; Tang, Wei-Hua; Zhao, Xing-Ming; Chen, Luonan

2010-01-01

117

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

118

Community support one pathway for small farmers to make a go of it in Vermont | Burlington Free Press | burlingtonfreepress.com http://www.burlingtonfreepress.com/article/20120531/BUSINESS08/120530041/1003/NEWS01/Community-support-one-pathway-small-farmer  

E-print Network

Community support one pathway for small farmers to make a go of it in Vermont | Burlington Free/120530041/1003/NEWS01/Community-support-one-pathway-small-farmers-make-go-Vermont?nclick_check=1[6/7/2012 3:52:41 PM] ADVERTISEMENT May 31, 2012 | Community support one pathway for small farmers to make a go of it in Vermont

Hayden, Nancy J.

119

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.

120

Original article Ecopathology in aquaculture  

E-print Network

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 ― ?copathologie en aquaculture

Paris-Sud XI, Université de

121

Stomata and pathogens  

PubMed Central

Bacteria and fungi are capable of triggering stomatal closure through pathogen-associated molecular patterns (PAMPs), which prevents penetration through these pores. Therefore, the stomata can be considered part of the plant innate immune response. Some pathogens have evolved mechanisms to evade stomatal defense. The bacterial pathogen Xanthomonas campestris pv. campestris (Xcc), which infects plants of the Brassicaceae family mainly through hydathodes, has also been reported to infect plants through stomata. A recent report shows that penetration of Xcc in Arabidopsis leaves through stomata depends on a secreted small molecule whose synthesis is under control of the rpf/diffusible signal factor (DSF) cell-to-cell signaling system, which also controls genes involved in biofilm formation and pathogenesis. The same reports shows that Arabidopsis ROS- and PAMP-activated MAP kinase 3 (MPK3) is essential for stomatal innate response. Other recent and past findings about modulation of stomatal behaviour by pathogens are also discussed. In all, these findings support the idea that PAMP-triggered stomatal closure might be a more effective and widespread barrier against phytopathogens than previously thought, which has in turn led to the evolution in pathogens of several mechanisms to evade stomatal defense. PMID:20514224

Gudesblat, Gustavo E; Torres, Pablo S

2009-01-01

122

he molecular basis of the pathogenicity of in-  

E-print Network

viruses such as HIV and intracellular bacterial pathogens such as Listeria and Salmonella, restricts growth and pathfinding, apoptosis and intra- and intercellular signalling pathways, to give but a few . The bacteria produce this toxin when they are cultured on high-osmolarity medium. If the nematode is exposed

Ewbank, Jonathan

123

Silicon and plant disease resistance against pathogenic fungi  

Microsoft Academic Search

Silicon (Si) is a bioactive element associated with beneficial effects on mechanical and physiological properties of plants. Silicon alleviates abiotic and biotic stresses, and increases the resistance of plants to pathogenic fungi. Several studies have suggested that Si activates plant defense mechanisms, yet the exact nature of the interaction between the element and biochemical pathways leading to resistance remains unclear.

James G. Menzies; Richard R. Blanger

2005-01-01

124

Food, pathogen, signal  

PubMed Central

C.elegans, both in the wild and in the lab, live on a diet of live bacteria. The bacterial diet provides nutrients for C. elegans, but can also play a number of other roles in C. elegans physiology. Recently, we compared the effects of different bacterial diets on life history traits and gene expression. Here, we discuss our recent findings in the context of other dietary studies and highlight challenges in understanding dietary effects. For instance, since bacteria can be pathogenic it can be difficult to disentangle pathogenic from dietary effects. Here we summarize different bacterial diets used for C. elegans and how they affect the animal. PMID:24744980

MacNeil, Lesley T; Walhout, Albertha JM

2013-01-01

125

The Keystone Pathogen Hypothesis  

PubMed Central

Recent studies have highlighted the importance of the human microbiome in host health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The keystone pathogen hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion, we critically assess the available literature in support of this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostic and treatment modalities for complex dysbiotic diseases. PMID:22941505

Hajishengallis, George; Darveau, Richard P.; Curtis, Michael A.

2012-01-01

126

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...

127

Leafhopper viral pathogens  

Technology Transfer Automated Retrieval System (TEKTRAN)

Four newly discovered viral pathogens in leafhopper vectors of Pierces 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...

128

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...

129

Immune pathways and defence mechanisms in honey bees Apis mellifera  

Microsoft Academic Search

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

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

130

In silico metabolic pathway modeling and analysis of Mycoplasma pneumoniae  

E-print Network

In silico metabolic pathway modeling and analysis of Mycoplasma pneumoniae Jin Sik Kim Sang Yup Lee-gu, Taejon 305-701, Korea Keywords: metabolic pathway modeling, Mycoplasma pneumoniae 1 Introduction of the metabolic model [2, 5]. Mycoplasma pneumoniae is a pathogen causing atypical pneumonia in human beings

131

Microbiota-mediated colonization resistance against intestinal pathogens  

PubMed Central

Commensal bacteria inhabit mucosal and epidermal surfaces in mice and humans, and have effects on metabolic and immune pathways in their hosts. Recent studies indicate that the commensal microbiota can be manipulated to prevent and even to cure infections that are caused by pathogenic bacteria, particularly pathogens that are broadly resistant to antibiotics, such as vancomycin-resistant Enterococcus faecium, Gram-negative Enterobacteriaceae and Clostridium difficile. In this Review, we discuss how immune- mediated colonization resistance against antibiotic-resistant intestinal pathogens is influenced by the composition of the commensal microbiota. We also review recent advances characterizing the ability of different commensal bacterial families, genera and species to restore colonization resistance to intestinal pathogens in antibiotic-treated hosts. PMID:24096337

Buffie, Charlie G.; Pamer, Eric G.

2014-01-01

132

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.

133

Killing them softly: managing pathogen polymorphism and virulence in spatially variable environments  

PubMed Central

Understanding why pathogen populations are genetically variable is vital because genetic variation fuels evolution, which often hampers disease control efforts. Here I argue that classical models of evolution in spatially variable environments specifically, models of hard and soft selection provide a useful framework to understand the maintenance of pathogen polymorphism and the evolution of virulence. First, the similarities between models of hard and soft selection and pathogen life cycles are described, highlighting how the type and timing of pathogen control measures impose density regulation that may affect both the level of pathogen polymorphism and virulence. The article concludes with an outline of potential lines of future theoretical and experimental work. PMID:23928098

Vale, Pedro F.

2013-01-01

134

Insect Vectors of Human Pathogens  

NSDL National Science Digital Library

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).

0000-00-00

135

Arabidopsis Jasmonate Signaling Pathway  

NSDL National Science Digital Library

Jasmonates control defense gene expression and male fertility in the model plant Arabidopsis thaliana. In both cases, the involvement of the jasmonate pathway is complex, involving large-scale transcriptional reprogramming. Additionally, jasmonate signaling is hard-wired into the auxin, ethylene, and salicylate signal networks, all of which are under intense investigation in Arabidopsis. In male fertility, jasmonic acid (JA) is the essential signal intervening both at the level of anther elongation and in pollen dehiscense. A number of genes potentially involved in jasmonate-dependent anther elongation have recently been discovered. In the case of defense, at least two jasmonates, JA and its precursor 12-oxo-phytodienoic acid (OPDA), are necessary for the fine-tuning of defense gene expression in response to various microbial pathogens and arthropod herbivores. However, only OPDA is required for full resistance to some insects and fungi. Other jasmonates probably affect yet more physiological responses. A series of breakthroughs have identified the SKP/CULLIN/F-BOX (SCF), CORONATINE INSENSITIVE (COI1) complex, acting together with the CONSTITUTIVE PHOTOMORPHOGENIC 9 (COP9) signalosome, as central regulatory components of jasmonate signaling in Arabidopsis. The studies, mostly involving mutational approaches, have paved the way for suppressor screens that are expected to further extend our knowledge of jasmonate signaling. When these and other new mutants affecting jasmonate signaling are characterized, new nodes will be added to the Arabidopsis Jasmonate Signaling Pathway Connections Map, and the lists of target genes regulated by jasmonates in Arabidopsis will be expanded.

Aurelie Gfeller (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV); Robin Liechti (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV); Edward E. Farmer (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV)

2006-02-14

136

Multiplex detection of agricultural pathogens  

DOEpatents

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.

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

2010-09-14

137

Multiplex detection of agricultural pathogens  

DOEpatents

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.

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

2013-01-15

138

PATHOGENIC ESCHERICHIA COLI IN FOODS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Pathogenic Escherichia coli are defined as those E. coli strains that are capable of causing diarrhoeal disease in humans. Subdivision of the pathogenic forms is made on the basis of the mechanism underlying the illness. Presently, four types of pathogenic E. coli have been implicated in foodborne...

139

Pathogenicity Islands in Bacterial Pathogenesis  

PubMed Central

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

Schmidt, Herbert; Hensel, Michael

2004-01-01

140

Chitosan against cutaneous pathogens  

PubMed Central

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

2013-01-01

141

Adhesion by Pathogenic Corynebacteria  

Microsoft Academic Search

\\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

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

142

Ubiquitin pathway and ovarian cancer  

PubMed Central

The ubiquitinproteasome pathway is a common cellular process in eukaryotic tissue. Ubiquitin binds to proteins and tags them for destruction; this tagging directs proteins to the proteosome in the cell that degrades and recycles unneeded proteins. The ubiquitinproteasome pathway plays an important role in the regulation of cellular proteins with respect to cell cycle control, transcription, apoptosis, cell adhesion, angiogenesis, and tumour growth. This review article discusses the various ways that the ubiquitin pathway is involved in ovarian cancer, such as modulating the ovarian-cancer-related gene BRCA1 and tumour suppressor p53, and interfering with the erk pathway, the cyclin-dependent cell cycle regulation process, and ERBB2 gene expression. PMID:23300358

Rao, Z.; Ding, Y.

2012-01-01

143

Aquatic eutrophication promotes pathogenic infection in amphibians  

PubMed Central

The widespread emergence of human and wildlife diseases has challenged ecologists to understand how large-scale agents of environmental change affect hostpathogen interactions. Accelerated eutrophication of aquatic ecosystems owing to nitrogen and phosphorus enrichment is a pervasive form of environmental change that has been implicated in the emergence of diseases through direct and indirect pathways. We provide experimental evidence linking eutrophication and disease in a multihost parasite system. The trematode parasite Ribeiroia ondatrae sequentially infects birds, snails, and amphibian larvae, frequently causing severe limb deformities and mortality. Eutrophication has been implicated in the emergence of this parasite, but definitive evidence, as well as a mechanistic understanding, have been lacking until now. We show that the effects of eutrophication cascade through the parasite life cycle to promote algal production, the density of snail hosts, and, ultimately, the intensity of infection in amphibians. Infection also negatively affected the survival of developing amphibians. Mechanistically, eutrophication promoted amphibian disease through two distinctive pathways: by increasing the density of infected snail hosts and by enhancing per-snail production of infectious parasites. Given forecasted increases in global eutrophication, amphibian extinctions, and similarities between Ribeiroia and important human and wildlife pathogens, our results have broad epidemiological and ecological significance. PMID:17893332

Johnson, Pieter T. J.; Chase, Jonathan M.; Dosch, Katherine L.; Hartson, Richard B.; Gross, Jackson A.; Larson, Don J.; Sutherland, Daniel R.; Carpenter, Stephen R.

2007-01-01

144

Stress Response and Pathogenicity of the Necrotrophic Fungal Pathogen Alternaria alternata  

PubMed Central

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

Chung, Kuang-Ren

2012-01-01

145

PIPS: Pathogenicity Island Prediction Software  

PubMed Central

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

Soares, Siomar C.; Abreu, Vincius 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

146

WRKY70 modulates the selection of signaling pathways in plant defense  

E-print Network

WRKY70 modulates the selection of signaling pathways in plant defense Jing Li, Gu¨nter Brader pathways is a central feature of the tightly regulated plant defense signaling network. The potential synergism or antagonism between defense pathways is determined by recognition of the type of pathogen

Palva, Tapio

147

Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens ?  

PubMed Central

The generation of an effective immune response against an infection while also limiting tissue damage requires a delicate balance between pro- and anti-inflammatory responses. Interleukin-10 (IL-10) has potent immunosuppressive effects and is essential for regulation of immune responses. However, the immunosuppressive properties of IL-10 can also be exploited by pathogens to facilitate their own survival. In this minireview, we discuss the role of IL-10 in modulating intracellular bacterial, fungal, and parasitic infections. Using information from several different infection models, we bring together and highlight some common pathways for IL-10 regulation and function that cannot be fully appreciated by studies of a single pathogen. PMID:21576331

Cyktor, Joshua C.; Turner, Joanne

2011-01-01

148

Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms  

PubMed Central

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

Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

2013-01-01

149

Advances in rapid detection methods for foodborne pathogens.  

PubMed

Food safety is increasingly becoming an important public health issue, as foodborne diseases present a widespread and growing public health problem in both developed and developing countries. The rapid and precise monitoring and detection of foodborne pathogens are some of the most effective ways to control and prevent human foodborne infections. Traditional microbiological detection and identification methods for foodborne pathogens are well known to be time consuming and laborious as they are increasingly being perceived as insufficient to meet the demands of rapid food testing. Recently, various kinds of rapid detection, identification, and monitoring methods have been developed for foodborne pathogens, including nucleic-acid-based methods, immunological methods, and biosensor-based methods, etc. This article reviews the principles, characteristics, and applications of recent rapid detection methods for foodborne pathogens. PMID:24375418

Zhao, Xihong; Lin, Chii-Wann; Wang, Jun; Oh, Deog Hwan

2014-03-28

150

Signaling Pathways in Cartilage Repair  

PubMed Central

In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. PMID:24837833

Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

2014-01-01

151

MICROBIOLOGY: Enhanced: Pathogenic Bacteria Prefer Heme  

NSDL National Science Digital Library

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.

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

2004-09-10

152

Review article Pathogenic role of gastric Helicobacter sp  

E-print Network

by Helicohac- ter heilmal1l1ii. feli.l' or pylnrf. Helicobacter / gastritis / dog / cat Résumé ― Rôle pylori whose role in the gen- eration of inflammatory antral gastritis and in the maintenance

Paris-Sud XI, Université de

153

Original article Pathogenic characteristics of persistent feline enteric  

E-print Network

in cats Liesbeth VOGEL 1 , Mariken VAN DER LUBBEN 1 , Eddie G. TE LINTELO 1 , Cornelis P.J. BEKKER 1 fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCo into the persistently infected state, are discussed. coronavirus / experimental infection / FECV / persistence / cat 1

Boyer, Edmond

154

[Bioterrorism and pathogenic microorganisms].  

PubMed

In recent years the use of pathogenic microorganisms in acts of bioterrorism has been the subject of major concern in many countries. This paper presents a possible application of viruses and bacteria for warfare and terrorist purposes, as well as a laboratory diagnosis to identify those agents. The viruses of smallpox (orthopoxvirus), of hemorrhagic fever and those belonging to filovirus have been highlighted, inter alia, as agents of human infection with bioterrorist intent. Among the bacteria, the emphasis has been on anthrax (Bacillus anthracis), the plague (Yersinia pestis), botulism (Clostridium botulinum) and tularemia (Francisella tularensis), not to mention ricin (Ricinus communis), as one of the Group B agents. PMID:24473660

Schatzmayr, Hermann G; Barth, Ortrud Monika

2013-10-01

155

Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes  

PubMed Central

Oxylipins are oxygenated metabolites of fatty acids. Eicosanoids are a subset of oxylipins and include the prostaglandins and leukotrienes, which are potent regulators of host immune responses. Host cells are one source of eicosanoids and oxylipins during infection; however, another potential source of eicosanoids is the pathogen itself. A broad range of pathogenic fungi, protozoa, and helminths produce eicosanoids and other oxylipins by novel synthesis pathways. Why do these organisms produce oxylipins? Accumulating data suggest that phase change and differentiation in these organisms are controlled by oxylipins, including prostaglandins and lipoxygenase products. The precise role of pathogen-derived eicosanoids in pathogenesis remains to be determined, but the potential link between pathogen eicosanoids and the development of TH2 responses in the host is intriguing. Mammalian prostaglandins and leukotrienes have been studied extensively, and these molecules can modulate Th1 versus Th2 immune responses, chemokine production, phagocytosis, lymphocyte proliferation, and leukocyte chemotaxis. Thus, eicosanoids and oxylipins (host or microbe) may be mediators of a direct host-pathogen cross-talk that promotes chronic infection and hypersensitivity disease, common features of infection by eukaryotic pathogens. PMID:12857780

Noverr, Mairi C.; Erb-Downward, John R.; Huffnagle, Gary B.

2003-01-01

156

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...

157

Characterization of plant fungal interactions involving necrotrophic effector-producing plant pathogens  

Technology Transfer Automated Retrieval System (TEKTRAN)

Recently, great strides have been made in the area of host-pathogen interactions involving necrotrophic fungi. In this article we describe a method to identify, produce, and characterize effectors that are important in host necrotrophic fungal pathogen interactions, and to genetically characterize...

158

Developmental Pathways in Juvenile Externalizing and Internalizing Problems  

ERIC Educational Resources Information Center

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

Loeber, Rolf; Burke, Jeffrey D.

2011-01-01

159

Cryptosporidium Pathogenicity and Virulence  

PubMed Central

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

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

2013-01-01

160

The Type I Interferon Pathway  

NSDL National Science Digital Library

The type I interferon (IFN-α/β) 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-α-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-α/β 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

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

2003-08-26

161

The Oxylipin Pathway in Arabidopsis  

PubMed Central

Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays. PMID:22303193

Creelman, Robert A.; Mulpuri, Rao

2002-01-01

162

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

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

Standiford, Richard B.

163

Genomic Target Database (GTD): A database of potential targets in human pathogenic bacteria  

PubMed Central

A Genomic Target Database (GTD) has been developed having putative genomic drug targets for human bacterial pathogens. The selected pathogens are either drug resistant or vaccines are yet to be developed against them. The drug targets have been identified using subtractive genomics approaches and these are subsequently classified into Drug targets in pathogen specific unique metabolic pathways,Drug targets in host-pathogen common metabolic pathways, andMembrane localized drug targets. HTML code is used to link each target to its various properties and other available public resources. Essential resources and tools for subtractive genomic analysis, sub-cellular localization, vaccine and drug designing are also mentioned. To the best of authors knowledge, no such database (DB) is presently available that has listed metabolic pathways and membrane specific genomic drug targets based on subtractive genomics. Listed targets in GTD are readily available resource in developing drug and vaccine against the respective pathogen, its subtypes, and other family members. Currently GTD contains 58 drug targets for four pathogens. Shortly, drug targets for six more pathogens will be listed. Availability GTD is available at IIOAB website http://www.iioab.webs.com/GTD.htm. It can also be accessed at http://www.iioabdgd.webs.com.GTD is free for academic research and non-commercial use only. Commercial use is strictly prohibited without prior permission from IIOAB. PMID:20011153

Barh, Debmalya; Kumar, Anil; Misra, Amarendra Narayana

2009-01-01

164

Multiplex detection of respiratory pathogens  

DOEpatents

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.

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

2012-07-31

165

Review article Consequences of environmental stress on oak  

E-print Network

Review article Consequences of environmental stress on oak: predisposition to pathogens PM Wargo by opportunistic pathogenic organisms that successfully invade and colonize stress-weakened trees. Oak trees also can act as a predisposing stress. Stress causes physical, physiological, and chemical changes

Paris-Sud XI, Université de

166

ARTICLE WATCH  

PubMed Central

This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, Hartwell Center, St. Jude Childrens Research Hospital, 332 North Lauderdale St., Memphis TN 38105-2794. Tel: (901) 495-4844; Fax: (901) 495-2945; email: Clive.Slaughter@stjude.org or to any member of the editorial board. Article summaries reflect the reviewers opinions and not necessarily those of the Association.

2007-01-01

167

Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica  

PubMed Central

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

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

2010-01-01

168

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

PubMed

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

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

2010-01-01

169

[Streptococcus pyogenes pathogenic factors].  

PubMed

The pathogenicity of -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

Bidet, Ph; Bonacorsi, S

2014-11-01

170

Fungal pathogens of Proteaceae.  

PubMed

Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand for the international floriculture market due to their brightly coloured and textured flowers or bracts. Fungal pathogens, however, create a serious problem in cultivating flawless blooms. The aim of the present study was to characterise several of these pathogens using morphology, culture characteristics, and DNA sequence data of the rRNA-ITS and LSU genes. In some cases additional genes such as TEF 1-? and CHS were also sequenced. Based on the results of this study, several novel species and genera are described. Brunneosphaerella leaf blight is shown to be caused by three species, namely B. jonkershoekensis on Protea repens, B. nitidae sp. nov. on Protea nitida and B. protearum on a wide host range of Protea spp. (South Africa). Coniothyrium-like species associated with Coniothyrium leaf spot are allocated to other genera, namely Curreya grandicipis on Protea grandiceps, and Microsphaeropsis proteae on P. nitida (South Africa). Diaporthe leucospermi is described on Leucospermum sp. (Australia), and Diplodina microsperma newly reported on Protea sp. (New Zealand). Pyrenophora blight is caused by a novel species, Pyrenophora leucospermi, and not Drechslera biseptata or D. dematoidea as previously reported. Fusicladium proteae is described on Protea sp. (South Africa), Pestalotiopsis protearum on Leucospermum cuneiforme (Zimbabwe), Ramularia vizellae and R. stellenboschensis on Protea spp. (South Africa), and Teratosphaeria capensis on Protea spp. (Portugal, South Africa). Aureobasidium leaf spot is shown to be caused by two species, namely A. proteae comb. nov. on Protea spp. (South Africa), and A. leucospermi sp. nov. on Leucospermum spp. (Indonesia, Portugal, South Africa). Novel genera and species elucidated in this study include Gordonomyces mucovaginatus and Pseudopassalora gouriqua (hyphomycetes), and Xenoconiothyrium catenata (coelomycete), all on Protea spp. (South Africa). PMID:22403475

Crous, P W; Summerell, B A; Swart, L; Denman, S; Taylor, J E; Bezuidenhout, C M; Palm, M E; Marincowitz, S; Groenewald, J Z

2011-12-01

171

Article type  

E-print Network

This Provisional 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. The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus

Erich M Schwarz; Pasi K Korhonen; Bronwyn E Campbell; Neil D Young; Aaron R Jex; Abdul Jabbar; Alinda Mondal; Adina C Howe; Jason Pell; Andreas Hofmann; Peter R Boag; Xing-quan Zhu; T Ryan Gregory; Alex Loukas; Brian A Williams; Igor Antoshechkin; C Titus Brown; Paul W Sternberg; Erich M Schwarz; Pasi K Korhonen; Bronwyn E Campbell; Neil D Young; Aaron R; Abdul Jabbar; Ross S Hall; Alinda Mondal; Adina C Howe; Jason Pell

2013-01-01

172

Article URL  

E-print Network

This Provisional 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. Th17 and Th22 cells in psoriatic arthritis and psoriasis

Helen Benham; Paul Norris; Jane Goodall; Mihir D Wechalekar; Oliver Fitzgerald; Agnes Szentpetery; Malcolm Smith; Ranjeny Thomas; Paul Norris; Jane Goodall; Mihir D Wechalekar; Oliver Fitzgerald; Agnes Szentpetery; Malcolm Smith; Ranjeny Thomas

2013-01-01

173

How technology drives pathogen discovery  

Microsoft Academic Search

Technological innovation in microbiology has been of supreme importance in the identifi- cation and study of pathogenic and non- pathogenic micro-organisms. The improvements that Anthony van Leeuwenhoek made to his single-lens microscope allowed him to observe bacteria for the first time in 1676. His report on oral microbiology to the Royal Society in 1684 enabled him to demonstrate that while

Paul Kellam; Robin A. Weiss

174

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 PECs membership on emerging pathogens, analytical methods, disinfection techniques, risk analysis, preparat...

175

Targeting the PI3K pathway for cancer therapy  

PubMed Central

The PI3K pathway plays an important role in key cellular functions such as cell growth, proliferation and survival. Genetic and epigenetic alterations in different pathway components lead to aberrant pathway activation and have been observed in high frequencies in various tumor types. Consequently, significant effort has been made to develop antineoplastic agents targeting different nodes in this pathway. Additionally, PI3K pathway status may have predictive and prognostic implications, and may contribute to drug resistance in tumor cells. This article provides an overview of our current knowledge of the PI3K pathway with an emphasis on its application in cancer treatment. PMID:22709255

Sadeghi, Navid; Gerber, David E

2014-01-01

176

Pathogenicity islands: the tip of the iceberg  

Microsoft Academic Search

Pathogenicity islands represent distinct genetic elements encoding virulence factors of pathogenic bacteria. Pathogenicity islands belong to the class of genomic islands, which are common genetic elements sharing a set of unifying features. Genomic islands have been acquired by horizontal gene transfer. In recent years many different genomic islands have been discovered in a variety of pathogenic as well as non-pathogenic

Ute Hentschel; Jrg Hacker

2001-01-01

177

Infection strategies of enteric pathogenic Escherichia coli  

PubMed Central

Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection. PMID:22555463

Clements, Abigail; Young, Joanna C.; Constantinou, Nicholas; Frankel, Gad

2012-01-01

178

Maintenance of Vacuole Integrity by Bacterial Pathogens  

PubMed Central

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

Creasey, Elizabeth A.; Isberg, Ralph R.

2014-01-01

179

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

PubMed

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

van der Veen, Stijn; Tang, Christoph M

2015-02-01

180

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

SciTech Connect

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.

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

181

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

NSDL National Science Digital Library

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.

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

2005-10-01

182

How Do Filamentous Pathogens Deliver Effector Proteins into Plant Cells?  

PubMed Central

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

Petre, Benjamin; Kamoun, Sophien

2014-01-01

183

Bacteria: More Than Pathogens  

NSDL National Science Digital Library

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 and a lesson: "Bacteria: Friend or Foe?"

Wassenaar, Trudy M.

2008-04-01

184

dbDiarrhea: the database of pathogen proteins and vaccine antigens from diarrheal pathogens.  

PubMed

Diarrhea occurs world-wide and is most commonly caused by gastrointestinal infections which kill around 2.2 million people globally each year, mostly children in developing countries. We describe here dbDiarrhea, which is currently the most comprehensive catalog of proteins implicated in the pathogenesis of diarrhea caused by major bacterial, viral and parasitic species. The current release of the database houses 820 proteins gleaned through an extensive and critical survey of research articles from PubMed. The major contributors to this compendium of proteins are Escherichia coli and Salmonella enterica. These proteins are classified into different categories such as Type III secretion system effectors, Type III secretion system components, and Pathogen proteins. There is another complementary module called 'Host proteins'. dbDiarrhea also serves as a repository of the research articles describing (1) trials of subunit and whole organism vaccines (2) high-throughput screening of Type III secretion system inhibitors and (3) diagnostic assays, for various diarrheal pathogens. The database is web accessible through an intuitive user interface that allows querying proteins and research articles for different organism, keywords and accession number. Besides providing the search facility through browsing, the database supports sequence similarity search with the BLAST tool. With the rapidly burgeoning global burden of the diarrhea, we anticipate that this database would serve as a source of useful information for furthering research on diarrhea. The database can be freely accessed at http://www.juit.ac.in/attachments/dbdiarrhea/diarrhea_home.html. PMID:22917656

Ramana, Jayashree; Tamanna

2012-12-01

185

In vitro pathogenicity assay for the ergot fungus Claviceps purpurea.  

PubMed

The pathogenic development of the biotrophic ergot fungus Claviceps purpurea is strictly limited to the ovary of grasses. Early colonization stages occur within a defined spatio-temporal course of events, including the directed growth to the vascular tissue for nutrient supply. To characterize mutant strains with putative defects in pathogenicity, the close observation of the infection pathway is therefore indispensable. Here, we describe the establishment of a new pathogenicity assay, based on the in vitro cultivation of isolated rye ovaries. The pathogenic development of a wild-type strain of C. purpurea was compared with the infection of mature rye flowers on whole plants. Up to the sixth day post inoculation, the route of infection within the isolated ovaries was maintained and temporally equal to that seen in mature flowers. Therefore, the in vitro pathogenicity assay is an effective alternative to the whole-plant infection tests, and suitable for detailed infection studies and screening high numbers of mutants for defects in early pathogenesis. PMID:16483754

Scheffer, Jan; Tudzynski, Paul

2006-04-01

186

Pathogens in Dairy Farming: Source Characterization and Groundwater Impacts  

NASA Astrophysics Data System (ADS)

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.

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

2007-12-01

187

The Francisella pathogenicity island.  

PubMed

The Francisella pathogenicity island (FPI) is a cluster of 16-19 genes, which is found duplicated in most of the Francisella genomes that have been sequenced. Although 16 FPI genes are highly conserved there are 2-3 putative genes that are absent or interrupted by stop codons in some strains. Francisella strains with experimentally induced mutations in FPI genes are highly attenuated in virulence and show defects in intramacrophage growth. There is experimental evidence indicating that the regulation of most FPI genes is affected by the presence of the virulence regulator MglA and by the concentration of iron in the growth medium. Although studies of mRNA expression show that essentially all FPI genes are transcribed, only a handful of FPI-encoded proteins have been detected by biochemical methods. The cumulative biochemical and genetic data to date have not yet been able to ascribe a biochemical function to any of the FPI-encoded proteins. However, bioinformatics analysis suggests that some of the FPI-encoded proteins are part of a type VI secretion system. PMID:17395722

Nano, Francis E; Schmerk, Crystal

2007-06-01

188

Transient virulence of emerging pathogens  

PubMed Central

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

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

2010-01-01

189

Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1.  

PubMed

Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns. However, these are produced by all microbes, regardless of their pathogenic potential. To distinguish virulent microbes from those with lower disease-causing potential the innate immune system detects conserved pathogen-induced processes, such as the presence of microbial products in the host cytosol, by mechanisms that are not fully resolved. Here we show that NOD1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases. Activation of RAC1 and CDC42 by bacterial delivery or ectopic expression of SopE, a virulence factor of the enteric pathogen Salmonella, triggered the NOD1 signalling pathway, with consequent RIP2 (also known as RIPK2)-mediated induction of NF-?B-dependent inflammatory responses. Similarly, activation of the NOD1 signalling pathway by peptidoglycan required RAC1 activity. Furthermore, constitutively active forms of RAC1, CDC42 and RHOA activated the NOD1 signalling pathway. Our data identify the activation of small Rho GTPases as a pathogen-induced process sensed through the NOD1 signalling pathway. PMID:23542589

Keestra, A Marijke; Winter, Maria G; Auburger, Josef J; Frssle, Simon P; Xavier, Mariana N; Winter, Sebastian E; Kim, Anita; Poon, Victor; Ravesloot, Maritta M; Waldenmaier, Julian F T; Tsolis, Rene M; Eigenheer, Richard A; Bumler, Andreas J

2013-04-11

190

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

Microsoft Academic Search

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,

Patrick J. Moran; Gary A. Thompson

2001-01-01

191

Legless pathogens: how bacterial physiology provides the key to understanding pathogenicity.  

PubMed

This review argues that knowledge of microbial physiology and metabolism is a prerequisite to understanding mechanisms of pathogenicity. The ability of Neisseria gonorrhoeae to cope with stresses such as those found during infection requires a sialyltransferase to sialylate its lipopolysaccharide using host-derived CMP-NANA in the human bloodstream, the ability to oxidize lactate that is abundant in the human body, outer-membrane lipoproteins that provide the first line of protection against oxidative and nitrosative stress, regulation of NO reduction independently from the nitrite reductase that forms NO, an extra haem group on the C-terminal extension of a cytochrome oxidase subunit, and a respiratory capacity far in excess of metabolic requirements. These properties are all normal components of neisserial physiology; they would all fail rigid definitions of a pathogenicity determinant. In anaerobic cultures of enteric bacteria, duplicate pathways for nitrate reduction to ammonia provide a selective advantage when nitrate is either abundant or scarce. Selection of these alternative pathways is in part regulated by two parallel two-component regulatory systems. NarX-NarL primarily ensures that nitrate is reduced in preference to thermodynamically less favourable terminal electron acceptors, but NarQ-NarP facilitates reduction of limited quantities of nitrate or other, less favourable, terminal electron acceptors in preference to fermentative growth. How enteric bacteria repair damage caused by nitrosative and oxidative damage inflicted by host defences is less well understood. In both N. gonorrhoeae and Escherichia coli, parallel pathways that duplicate particular biochemical functions are far from redundant, but fulfil specific physiological roles. PMID:22493300

Cole, Jeffrey A

2012-06-01

192

REVIEW ARTICLE published: 11 June 2013  

E-print Network

dependent on their ability to avoid and suppress plant defense responses most notably by secretion). Different effector proteins target specific components of plant defense and are effective only againstREVIEW ARTICLE published: 11 June 2013 doi: 10.3389/fpls.2013.00191 Pathogenicity of and plant

Palva, Tapio

193

Research Article Discrimination of Peromyscus maniculatus  

E-print Network

Proof Only Proof Only Research Article Discrimination of Peromyscus maniculatus Leukocytes by Flow Junction, CO 81501 Abstract. Deer mice (Peromyscus maniculatus) have been identified as the principal host of the genus Peromyscus host several human pathogens, including the agents of granulocytic ehrlichiosis, Lyme

Schountz, Tony

194

Published Articles:  

Cancer.gov

Published Articles Divisionof Extramural Activities Contacts | About | Exit Funding Patterns Awards of R01 and R21 Grants in FY 2014 Awards of R01 and R21 Grants in FY 2013 Awards of R01 and R21 Grants in FY 2012 Awards of R01 and R21 Grants in FY

195

Article URL  

E-print Network

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. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

David Pretzel; Stefanie Linss; Hannes Ahrem; Michaela Endres; Christian Kaps; Dieter Klemm; Raimund W. Kinne; David Pretzel; Stefanie Linss; Hannes Ahrem; Michaela Endres; Christian Kaps; Dieter Klemm; Raimund W Kinne

2013-01-01

196

Pathogenic Mechanisms of Pulmonary Arterial Hypertension  

PubMed Central

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

Chan, Stephen Y.; Loscalzo, Joseph

2008-01-01

197

The Evolution of the Wnt Pathway  

PubMed Central

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, anteriorposterior body axis, which can be traced throughout animal evolution. PMID:22751150

Holstein, Thomas W.

2012-01-01

198

HostPathogen Systems Biology  

Microsoft Academic Search

\\u000a Unlike traditional biological research that focuses on a small set of components, systems biology studies the complex interactions\\u000a among a large number of genes, proteins, and other elements of biological networks and systems. Host-pathogen systems biology\\u000a examines the interactions between the components of two distinct organisms: a microbial or viral pathogen and its animal host.\\u000a With the availability of complete

Christian V. Forst

199

NLR functions beyond pathogen recognition  

Microsoft Academic Search

The last 10 years have witnessed the identification of a new class of intracellular pattern-recognition moleculesthe nucleotide-binding domain and leucine-rich repeatcontaining family (NLR). Members of this family garnered interest as pattern-recognition receptors able to trigger inflammatory responses against pathogens. Many studies support a pathogen-recognition function for human NLR proteins and shed light on their role in the broader control of

Thomas A Kufer; Philippe J Sansonetti

2011-01-01

200

Differential expression of genes encoding calmodulin-binding proteins in response to bacterial pathogens and inducers of defense responses  

Microsoft Academic Search

Calmodulin (CaM) plays an important role in sensing and transducing changes in cellular Ca2+ concentration in response to several biotic and abiotic stresses. Although CaM is implicated in plant-pathogen interactions, its molecular targets and their role in defense signaling pathway(s) are poorly understood. To elucidate the signaling pathways that link CaM to defense responses, we screened a cDNA library constructed

Gul Shad Ali; Vaka S. Reddy; Peter B. Lindgren; Judy L. Jakobek; A. S. N. Reddy

2003-01-01

201

Volatile Metabolites of Pathogens: A Systematic Review  

PubMed Central

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

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

2013-01-01

202

Laminate article  

DOEpatents

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.

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

203

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

PubMed

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. PMID:11865865

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

2001-06-01

204

PathogenMip Assay: A Multiplex Pathogen Detection Assay  

PubMed Central

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

Akhras, Michael S.; Thiyagarajan, Sreedevi; Villablanca, Andrea C.; Davis, Ronald W.; Nyrn, Pl; Pourmand, Nader

2007-01-01

205

The Aedes aegypti Toll Pathway Controls Dengue Virus Infection  

Microsoft Academic Search

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

Zhiyong Xi; Jose L. Ramirez; George Dimopoulos

2008-01-01

206

Host Response to Respiratory Bacterial Pathogens as Identified by Integrated Analysis of Human Gene Expression Data  

PubMed Central

Respiratory bacterial pathogens are one of the leading causes of infectious death in the world and a major health concern complicated by the rise of multi-antibiotic resistant strains. Therapeutics that modulate host genes essential for pathogen infectivity could potentially avoid multi-drug resistance and provide a wider scope of treatment options. Here, we perform an integrative analysis of published human gene expression data generated under challenges from the gram-negative and Gram-positive bacteria pathogens, Pseudomonas aeruginosa and Streptococcus pneumoniae, respectively. We applied a previously described differential gene and pathway enrichment analysis pipeline to publicly available host mRNA GEO datasets resulting from exposure to bacterial infection. We found 72 canonical human pathways common between four GEO datasets, representing P. aeruginosa and S. pneumoniae. Although the majority of these pathways are known to be involved with immune response, we found several interesting new interactions such as the SUMO1 pathway that might have a role in bacterial infections. Furthermore, 36 host-bacterial pathways were also shared with our previous results for respiratory virus host gene expression. Based on our pathway analysis we propose several drug-repurposing opportunities supported by the literature. PMID:24086587

Smith, Steven B.; Magid-Slav, Michal; Brown, James R.

2013-01-01

207

Waterborne protozoan pathogens.  

PubMed Central

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

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

1997-01-01

208

New insights into the regulation of plant immunity by amino acid metabolic pathways.  

PubMed

Besides defence pathways regulated by classical stress hormones, distinct amino acid metabolic pathways constitute integral parts of the plant immune system. Mutations in several genes involved in Asp-derived amino acid biosynthetic pathways can have profound impact on plant resistance to specific pathogen types. For instance, amino acid imbalances associated with homoserine or threonine accumulation elevate plant immunity to oomycete pathogens but not to pathogenic fungi or bacteria. The catabolism of Lys produces the immune signal pipecolic acid (Pip), a cyclic, non-protein amino acid. Pip amplifies plant defence responses and acts as a critical regulator of plant systemic acquired resistance, defence priming and local resistance to bacterial pathogens. Asp-derived pyridine nucleotides influence both pre- and post-invasion immunity, and the catabolism of branched chain amino acids appears to affect plant resistance to distinct pathogen classes by modulating crosstalk of salicylic acid- and jasmonic acid-regulated defence pathways. It also emerges that, besides polyamine oxidation and NADPH oxidase, Pro metabolism is involved in the oxidative burst and the hypersensitive response associated with avirulent pathogen recognition. Moreover, the acylation of amino acids can control plant resistance to pathogens and pests by the formation of protective plant metabolites or by the modulation of plant hormone activity. PMID:23611692

Zeier, Jrgen

2013-12-01

209

Edinburgh Research Explorer Highly pathogenic or low pathogenic avian influenza virus  

E-print Network

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

Millar, Andrew J.

210

Comparative metabolic systems analysis of pathogenic Burkholderia.  

PubMed

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

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

2014-01-01

211

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

PubMed Central

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

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

2013-01-01

212

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

PubMed Central

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

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

2014-01-01

213

Proteomics of Plant Pathogenic Fungi  

PubMed Central

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

Gonzlez-Fernndez, Raquel; Prats, Elena; Jorrn-Novo, Jess V.

2010-01-01

214

The Main Aeromonas Pathogenic Factors  

PubMed Central

The members of the Aeromonas genus are ubiquitous, water-borne bacteria. They have been isolated from marine waters, rivers, lakes, swamps, sediments, chlorine water, water distribution systems, drinking water and residual waters; different types of food, such as meat, fish, seafood, vegetables, and processed foods. Aeromonas strains are predominantly pathogenic to poikilothermic animals, and the mesophilic strains are emerging as important pathogens in humans, causing a variety of extraintestinal and systemic infections as well as gastrointestinal infections. The most commonly described disease caused by Aeromonas is the gastroenteritis; however, no adequate animal model is available to reproduce this illness caused by Aeromonas. The main pathogenic factors associated with Aeromonas are: surface polysaccharides (capsule, lipopolysaccharide, and glucan), S-layers, iron-binding systems, exotoxins and extracellular enzymes, secretion systems, fimbriae and other nonfilamentous adhesins, motility and flagella. PMID:23724321

Toms, J. M.

2012-01-01

215

Manipulation of small Rho GTPases is a pathogen-induced process detected by Nod1  

PubMed Central

Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns (PAMPs) 1. However, all microbes produce PAMPs, regardless of their pathogenic potential. To distinguish virulent microbes from ones with lower disease-causing potential the innate immune system detects conserved pathogen-induced processes 2, such as the presence of microbial products in the host cytosol, by mechanisms that are not fully resolved. Here we show that Nod1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases. Activation of Rac1 and Cdc42 by bacterial delivery or ectopic expression of a Salmonella virulence factor, SopE, triggered the Nod1 signaling pathway with consequent Rip2-mediated induction of NF-?B-dependent inflammatory responses. Similarly, activation of the Nod1 signaling pathway by peptidoglycan required Rac1 activity. Furthermore, constitutively active forms of Rac1, Cdc42 and RhoA activated the Nod1 signaling pathway. Our data identify activation of small Rho GTPases as a pathogen-induced process sensed through the Nod1 signaling pathway (Fig. S1). PMID:23542589

Keestra, A. Marijke; Winter, Maria G.; Auburger, Josef J.; Frle, Simon P.; Xavier, Mariana N.; Winter, Sebastian E.; Kim, Anita; Poon, Victor; Ravesloot, Maritta M.; Waldenmaier, Julian; Tsolis, Rene M.; Eigenheer, Richard A.; Bumler, Andreas J.

2013-01-01

216

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

PubMed Central

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

Giles, Peter F.; Soanes, Darren M.

2003-01-01

217

Induced resistance enzymes in wild plantsdo early birds escape from pathogen attack?  

Microsoft Academic Search

Systemic acquired resistance (SAR) of plants to pathogens is a well-defined phenomenon. The underlying signalling pathways and its application in crop protection are intensively studied. However, most studies are conducted on crop plants or on Arabidopsis as a model plant. The taxonomic distribution of this phenomenon and its dependence on life history are thus largely unknown. We quantified activities of

Martin Heil; Kerstin Ploss

2006-01-01

218

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

NSDL National Science Digital Library

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.

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

1996-01-26

219

An imprinted rheumatoid arthritis methylome signature reflects pathogenic phenotype  

PubMed Central

Background A DNA methylation signature has been characterized that distinguishes rheumatoid arthritis (RA) fibroblast like synoviocytes (FLS) from osteoarthritis (OA) FLS. The presence of epigenetic changes in long-term cultured cells suggest that rheumatoid FLS imprinting might contribute to pathogenic behavior. To understand how differentially methylated genes (DMGs) might participate in the pathogenesis of RA, we evaluated the stability of the RA signature and whether DMGs are enriched in specific pathways and ontology categories. Methods To assess the RA methylation signatures the Illumina HumanMethylation450 chip was used to compare methylation levels in RA, OA, and normal (NL) FLS at passage 3, 5, and 7. Then methylation frequencies at CpGs within the signature were compared between passages. To assess the enrichment of DMGs in specific pathways, DMGs were identified as genes that possess significantly differential methylated loci within their promoter regions. These sets of DMGs were then compared to pathway and ontology databases to establish enrichment in specific categories. Results Initial studies compared passage 3, 5, and 7 FLS from RA, OA, and NL. The patterns of differential methylation of each individual FLS line were very similar regardless of passage number. Using the most robust analysis, 20 out of 272 KEGG pathways and 43 out of 34,400 GO pathways were significantly altered for RA compared with OA and NL FLS. Most interestingly, we found that the KEGG 'Rheumatoid Arthritis' pathway was consistently the most significantly enriched with differentially methylated loci. Additional pathways involved with innate immunity (Complement and Coagulation, Toll-like Receptors, NOD-like Receptors, and Cytosolic DNA-sensing), cell adhesion (Focal Adhesion, Cell Adhesion Molecule), and cytokines (Cytokine-cytokine Receptor). Taken together, KEGG and GO pathway analysis demonstrates non-random epigenetic imprinting of RA FLS. Conclusions The DNA methylation patterns include anomalies in key genes implicated in the pathogenesis of RA and are stable for multiple cell passages. Persistent epigenetic alterations could contribute to the aggressive phenotype of RA synoviocytes and identify potential therapeutic targets that could modulate the pathogenic behavior. PMID:23631487

2013-01-01

220

New trends in emerging pathogens.  

PubMed

The emergence of pathogens is the result of a number of impact in all parts of the food chain. The emerging technologies in food production explain how new pathogens can establish themselves in the food chain and compromise food safety. The impact of the food technology is analysed for several bacteria, such as Yersinia, Campylobacter, Arcobacter, Helicobacter pullorum, Enterobacter sakazakii, Mycobacterium avium spp. paratuberculosis, prions related to vCJD and others. The importance of the ability of many microbes to form VBNC forms is elaborated on. Research on culture independent methods may address this outstanding issue to the better understanding of emerging pathogens. The "demerging" of pathogens also occur, and examples of this are explained. The reaction of bacteria to stresses and sublethal treatments, and how exposure to one stress factor can confer resistance to other stresses, literally speaking causing contagious resistance, are explained. The implication of this e.g. in modern approaches of food preservation, such as Minimally processed Foods, is considerable. Intestinal colonization of EHEC may be regulated by Quorum sensing, and this ability of microbes plays an important role in the colonization of microbes in food and on food processing equipment, an important factor in the emergence of pathogens. The emergence of Saccharomyces cerevisiae, as an opportunistic human pathogen, used for centuries for food and production of alcoholic beverages, calls for research in molecular tools to distinguish between probiotic and clinical strains. Cyclospora cayetanensis and Norovirus outbreaks can no longer be designated as emerging pathogens, they share however one characteristic in the epidemiology of emerging nature, the importance of the hygiene in the primary production stage, including supply of potable water, and the application of GMP and the HACCP principles in the beginning of the food chain. Hepatitis E virus is a potential emerging food borne pathogen and swine may serve as a source of infection in human, a most challenging issue in greater part of the world raising pigs. Tick-borne encephalitis virus infection, either thick borne or caused by consumption of raw milk, is an increasing trend in the industrialized part of the world. Consumer awareness, ethics of food, sustainability in food production, and trust in foods, are of growing importance to the consumer. The reaction of the consumer to new technology, such as nanotechnology, is unpredictable. Many efforts should be devoted to communication of non-biased information to both the food producers as well as the consumer. PMID:17976849

Skovgaard, Niels

2007-12-15

221

Cellular defense processes regulated by pathogen-elicited receptor signaling  

NASA Astrophysics Data System (ADS)

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.

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

2011-06-01

222

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

223

Pathogenic microbes and community service through manipulation of innate immunity  

PubMed Central

The periodontal pathogen Porphyromonas gingivalis undermines major components of innate immunity, such as complement, Toll-like receptors (TLR), and their crosstalk pathways. At least in principle, these subversive activities could promote the adaptive fitness of the entire periodontal biofilm community. In this regard, the virulence factors responsible for complement and TLR exploitation (gingipain enzymes, atypical lipopolysaccharide molecules, and fimbriae) are released as components of readily diffusible membrane vesicles, which can thus become available to other biofilm organisms. This review summarizes important immune subversive tactics of P. gingivalis which might enable it to exert a supportive impact on the oral microbial community. PMID:21948363

Hajishengallis, George; Krauss, Jennifer L.; Liang, Shuang; McIntosh, Megan L.; Lambris, John D.

2011-01-01

224

Glucanase Induces Filamentation of the Fungal Pathogen Candida albicans  

PubMed Central

Candida albicans is the most common human fungal pathogen. Many organisms, including C. albicans, secrete glucanases under different environmental conditions. Here, we report a novel role for beta-1, 3- glucanase in inducing Candida albicans to form filaments at 22C and enhancing filamentation at 37C in nutrient-rich medium. Quorum sensing, the efg1-signaling and cek1 MAP kinase pathways are involved in this process. Our data suggest that the natural antifungal agent betaglucanase may support morphologic transformation of Candida albicans at a wide range of ambient temperatures. PMID:23737947

Xu, Hongbin; Nobile, Clarissa J.; Dongari-Bagtzoglou, Anna

2013-01-01

225

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

PubMed Central

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

Yoon, Jeong-Yeol; Kim, Bumsang

2012-01-01

226

[Notch signal pathway and chronic lymphocytic leukemia].  

PubMed

Chronic lymphocytic leukemia (CLL), an indolent B-cell malignancy, is characterized by heterogeneity of the clinical course. Notch signaling pathway is an evolutionarily conserved signaling pathway and involved in the normal regulation of cell survival, proliferation, differentiation, apoptosis and other physiological processes. In recent years, more and more researchers study the relationship between Notch signaling pathway and chronic lymphocytic leukemia and have found that Notch molecules present in CLL cells with high expression or mutation, which associated with the prognosis, anti-apoptosis, drug-resistance and so on. In this article, the recent advances of studies on CLL and Notch pathway, including the expression level of Notch molecules in CLL cells, the anti-apoptosis and drug-resistance of Notch molecules in CLL cells, the mutation of Notch molecules in CLL cells, the relation of Notch molecules with CLL prognosis and the application prospect of Notch molecule inhibitors are reviewed. PMID:25338610

Zhang, Jin Yan; Xu, Zhen Shu

2014-10-01

227

Hedgehog Signaling Pathway  

NSDL National Science Digital Library

The Hedgehog (Hh) signaling pathway is essential for development and tissue homeostasis in metazoans. Probably as a result of its potent influence on cell-fate outcomes, the Hh pathway when corrupted results in malformations and diseases such as cancer. Many of the pathway components that contribute to Hh-mediated signal transduction are presented.

Leni Jacob (University of Texas Southwestern Medical Center; Department of Cell Biology REV)

2007-10-09

228

Methods for the discovery of emerging pathogens.  

PubMed

Recently, there has been a steady increase in the number of recognized pathogenic microorganisms, specifically bacteria. The development of genetic technologies, MALDI-TOF mass spectrometry and new culturing techniques has significantly widened the repertoire of known microorganisms and therefore pathogenic microorganisms. The repertoire of infectious agents has been studied in various environments including water, soil, pets, livestock, wildlife and arthropods. Using different methods, many known pathogens can be identified in these samples; therefore, the impact of emergent pathogens on humans can be examined and novel pathogens can be identified. In this special issue, we discuss the identification of emerging pathogens in the environment and animals. PMID:25014736

Angelakis, Emmanouil; Raoult, Didier

2014-12-01

229

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 ...

230

Proteomics of foodborne bacterial pathogens  

Technology Transfer Automated Retrieval System (TEKTRAN)

This chapter focuses on recent research on foodborne bacterial pathogens that use mass spectrometry-based proteomic techniques as well as protein microarrays. Mass spectrometry ionization techniques (e.g. electrospray ionization and matrix-assisted laser desorption/ionization), analyzers (e.g. ion ...

231

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...

232

USEPA PERSPECTIVE ON CONTROLLING PATHOGENS  

EPA Science Inventory

EPA minimizes the risk of infectious diseases from the beneficial use of sludge by requiring its treatment to reduce pathogen levels below the detection limit. How new treatment processes can be shown equivalent to ones specified in 40CFR503 will be discussed together with ways t...

233

PATHOGEN SURVEILLANCE: Designs and Analyses  

E-print Network

;4 Individual vs. Population What conclusions can be made?What conclusions can be made? Uses and Benefits Pathogen Prevalence Level (APPL) ·Estimated Host Population Size ·Confidence in detection (95%) Population Size 10% APPL 5% APPL 2% APPL 50 100 250 500 2000 >100,000 20 23 25 26 27 30 35 45 50 55 60 60 50 75

Gray, Matthew

234

Pathogen Microevolution in High Resolution  

Microsoft Academic Search

Microbial genomics has revolutionized infectious diseases and epidemiology research and is facilitating the tracking and containment of emerging biological threats. Among the most serious contemporary infectious agents are multiple antibiotic-resistant strains of the human pathogen Staphylococcus aureus, which present a formidable public health challenge that is no longer limited to hospitalized patients. To address key hypotheses regarding microbial strain evolution

Ramy K. Aziz; Victor Nizet

2010-01-01

235

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...

236

Nuclear jasmonate and salicylate signaling and crosstalk in defense against pathogens  

PubMed Central

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 plants hormone signaling network to promote disease. PMID:23577014

Gimenez-Ibanez, Selena; Solano, Roberto

2013-01-01

237

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

PubMed Central

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

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

2014-01-01

238

A Rab-centric perspective of bacterial pathogen-occupied vacuoles  

PubMed Central

Summary The ability to create and maintain a specialized organelle that supports bacterial replication is an important virulence property for many intracellular pathogens. Living in a membrane-bound vacuole presents inherent challenges including the need to remodel a plasma membrane-derived organelle into a novel structure that will expand and provide essential nutrients to support replication, while also having the vacuole avoid membrane transport pathways that target bacteria for destruction in lysosomes. It is clear that pathogenic bacteria use different strategies to accomplish these tasks. The dynamics by which host Rab GTPases associate with pathogen-occupied vacuoles provides insight into the mechanisms used by different bacteria to manipulate host membrane transport. In this review we highlight some of the strategies bacteria use to maintain a pathogen-occupied vacuole by focusing on the Rab proteins involved in biogenesis and maintenance of these novel organelles. PMID:24034612

Sherwood, Racquel Kim; Roy, Craig R.

2013-01-01

239

Research Article  

E-print Network

Copyright 2011 S. Saska et al. 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 aim of this study was to develop and to evaluate the biological properties of bacterial cellulose-hydroxyapatite (BC-HA) nanocomposite membranes for bone regeneration. Nanocomposites were prepared from bacterial cellulose membranes sequentially incubated in solutions of CaCl2 followed by Na2HPO4. BC-HA membranes were evaluated in noncritical bone defects in rat tibiae at 1, 4, and 16 weeks. Thermogravimetric analyses showed that the amount of the mineral phase was 40%50 % of the total weight. Spectroscopy, electronic microscopy/energy dispersive X-ray analyses, and X-ray diffraction showed formation of HA crystals on BC nanofibres. Low crystallinity HA crystals presented Ca/P a molar ratio of 1.5 (calcium-deficient HA), similar to physiological bone. Fourier transformed infrared spectroscopy analysis showed bands assigned to phosphate and carbonate ions. In vivo tests showed no inflammatory reaction after 1 week. After 4 weeks, defects were observed to be completely filled in by new bone tissue. The BC-HA membranes were effective for bone regeneration. 1.

Bacterial Cellulose-hydroxyapatite Nanocomposites For; Bone Regeneration

240

Organomercury Pathway Map  

NSDL National Science Digital Library

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.

Nasevicius, Aidas.

241

The Molecular Pathogenicity of Fusarium Keratitis  

PubMed Central

Purpose The pathogenic mechanisms of fungal infection during human keratomycosis were investigated in an ex vivo corneal model that used strains of Fusarium oxysporum differing in the production of a fungal transcription factor. Methods A pacC- loss-of-function mutant and a pacCc dominant-activating mutant were constructed from a wild-type isolate of F. oxysporum, and the three strains were characterized by in vitro growth kinetics. Twenty-seven human donor corneas maintained in tissue culture were superficially scarified and topically inoculated with the wild-type, the pacC- loss-of-function mutant, or the pacCc dominant-activating strain. Relative hyphal invasion into the stroma was compared histopathologically in corneal sections. Results F. oxysporum strains demonstrated comparable exponential growth rates in vitro. Wild-type F. oxysporum invaded into corneal tissue within one day and penetrated through the anterior stroma during the next 4 days. The pacC- loss-of-function mutant invaded explanted corneas significantly less than the wild-type on day 1 (P<0.0001) and on day 3 (P=0.0003). The pacCc dominant-activating strain adhered and penetrated explanted corneas similar to the wild-type strain. Conclusion The PacC pathway regulating the transcription of fungal genes allows fungal adaptation to the ocular surface and enables invasion of the injured cornea by F. oxysporum. PMID:20856109

Hua, Xia; Yuan, Xiaoyong; Di Pietro, Antonio; Wilhelmus, Kirk R.

2010-01-01

242

Laribacter hongkongensis: an emerging pathogen of infectious diarrhea.  

PubMed

Laribacter hongkongensis is relatively a new name in the list of bacterial pathogens for gastroenteritis and travelers' diarrhea. Addition of another name increases burden on the enteric infections as a whole. L. hongkongensis belongs to Neisseriaceae family of ? subclass Proteobacteria. L. hongkongensis was initially isolated in Hong Kong from blood and empyema of an alcoholic cirrhotic patient in 2001, followed by reports from Korea and China, representing a total of 38 articles in PubMed until April 2013. As of now, there is no report from Indian subcontinent where infectious diarrhea is very much prevalent and a major burden. This review provides information about the microbiological characteristics, consideration of an emerging pathogen, relative pathogenicity, genome and proteome content, resistance toward multiple antibiotics, adaptability to different stress, and other features since its time of discovery. Investigation for this bacterium may avoid misidentification as other microbial flora. Further studies like the geographical distribution, type of infection, disease burden, pathogenicity, or genomic exploration of this bacterium will be useful in characterizing them properly. This bacterium may possibly be the emerging threat to public health. PMID:24481985

Raja, M Krishna; Ghosh, Asit Ranjan

2014-07-01

243

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

PubMed

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

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

2015-01-28

244

Identifying pathogenicity genes in the rubber tree anthracnose fungus Colletotrichum gloeosporioides through random insertional mutagenesis.  

PubMed

To gain more insight into the molecular mechanisms of Colletotrichum gloeosporioides pathogenesis, Agrobacterium tumefaciens-mediated transformation (ATMT) was used to identify mutants of C. gloeosporioides impaired in pathogenicity. An ATMT library of 4128 C. gloeosporioides transformants was generated. Transformants were screened for defects in pathogenicity with a detached copper brown leaf assay. 32 mutants showing reproducible pathogenicity defects were obtained. Southern blot analysis showed 60.4% of the transformants had single-site T-DNA integrations. 16 Genomic sequences flanking T-DNA were recovered from mutants by thermal asymmetric interlaced PCR, and were used to isolate the tagged genes from the genome sequence of wild-type C. gloeosporioides by Basic Local Alignment Search Tool searches against the local genome database of the wild-type C. gloeosporioides. One potential pathogenicity genes encoded calcium-translocating P-type ATPase. Six potential pathogenicity genes had no known homologs in filamentous fungi and were likely to be novel fungal virulence factors. Two putative genes encoded Glycosyltransferase family 28 domain-containing protein and Mov34/MPN/PAD-1 family protein, respectively. Five potential pathogenicity genes had putative function matched with putative protein of other Colletotrichum species. Two known C. gloeosporioides pathogenicity genes were also identified, the encoding Glomerella cingulata hard-surface induced protein and C. gloeosporioides regulatory subunit of protein kinase A gene involved in cAMP-dependent PKA signal transduction pathway. PMID:23602122

Cai, Zhiying; Li, Guohua; Lin, Chunhua; Shi, Tao; Zhai, Ligang; Chen, Yipeng; Huang, Guixiu

2013-07-19

245

RESEARCH ARTICLE Modeling population connectivity by ocean currents,  

E-print Network

RESEARCH ARTICLE Modeling population connectivity by ocean currents, a graph-theoretic approach species, population connectivity is determined largely by ocean currents transporting larvae and juveniles). Patterns in the dispersal graphs highlight pathways for larval dispersal along major ocean currents

Queensland, University of

246

Analyzing Pathogen Populations Using Molecular Markers  

Microsoft Academic Search

DNA probes are useful markers for studying pathogen population genetics. Repetitive probes may produce characteristic fingerprints\\u000a that identify strains or lineages of asexually-reproducing pathogens. Relatedness among strains can be inferred, giving insight\\u000a into the processes of race evolution, gene flow, and other aspects of pathogen population biology. Information about pathogen\\u000a population dynamics may be useful in designing improved strategies for

Rebecca J. Nelson

247

Response of soybean pathogens to glyceollin  

Technology Transfer Automated Retrieval System (TEKTRAN)

The ability to recognize pathogens and respond biochemically to prevent or inhibit pathogen invasion and colonization in plant cells is an active disease resistance response in plants. The involvement of soybean phytoalexin glyceollin in defense responses to the soybean pathogens Diaporthe phaseolor...

248

DETERMINANTS OF CONSUMER AWARENESS OF FOODBORNE PATHOGENS  

Microsoft Academic Search

Each year, microbial pathogens cause millions of cases of foodborne disease and result in many hospitalizations and deaths. Effective consumer education programs to promote safer food handling practices and other averting behaviors may benefit from consumer awareness of microbial pathogens. This paper investigates U.S. consumers?' awareness of four major microbial pathogens (Salmonella, Campylobacter, Listeria and E. coli) as food safety

Chung-Tung Jordan Lin; Kimberly L. Jensen; Steven T. Yen

2004-01-01

249

Awareness of foodborne pathogens among US consumers  

Microsoft Academic Search

Each year in the United States, microbial pathogens cause millions of cases of foodborne disease and result in many hospitalizations and deaths. Effective consumer education programs to promote safer food handling practices and other averting behaviors may benefit from consumer awareness of microbial pathogens. This paper investigates US consumers awareness of four major microbial pathogens (Salmonella, Campylobacter, Listeria and Escherichia

Chung-Tung Jordan Lin; Kimberly L. Jensen; Steven T. Yen

2005-01-01

250

77 FR 34783 - Highly Pathogenic Avian Influenza  

Federal Register 2010, 2011, 2012, 2013, 2014

...RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant Health Inspection...any subtype of highly pathogenic avian influenza (HPAI) is considered to exist. The...Newcastle disease and highly pathogenic avian influenza (HPAI). On January 24, 2011,...

2012-06-12

251

Review article Cardioprotective signaling to mitochondria  

E-print Network

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

Brand, Paul H.

252

Lagenidium giganteum Pathogenicity in Mammals.  

PubMed

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 25C and 37C, whereas the biological control strains developed normally at 25C 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

Vilela, Raquel; Taylor, John W; Walker, Edward D; Mendoza, Leonel

2015-02-01

253

Lagenidium giganteum Pathogenicity in Mammals  

PubMed Central

Infections of mammals by species in the phylum Oomycota taxonomically and molecularly similar to known Lagenidium giganteum strains have increased. During 20132014, 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 25C and 37C, whereas the biological control strains developed normally at 25C 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

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

2015-01-01

254

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

255

How do pathogens drive the evolution of paired receptors?  

PubMed

Paired receptors are families of membrane proteins characterized by similar extracellular regions but different transmembrane and cytoplasmic regions, meaning that some members can give inhibitory signals and others activating signals. Well-characterized examples include the KIR, SIRP, Ly49, Nkpr, and Siglec families. The difference in the repertoire of these genes in mouse and man indicates that these families have evolved rapidly. For example, KIRs are found in humans and not mice, and Ly49 shows the converse. These genes are often very polymorphic, e.g. KIR and the number of genes can vary as shown for Ly49 in different mouse strains. Paired receptors are expressed mainly on NK and myeloid cells and their evolution is thought to be pathogen driven. In this article, we review various receptor families for which pathogen interactions are known and discuss the possible molecular mechanisms driving their evolution. PMID:23280392

Akkaya, Munir; Barclay, A Neil

2013-02-01

256

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

PubMed

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

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

2013-03-15

257

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

PubMed Central

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 proteinprotein 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

Banfield, Mark J

2015-01-01

258

Molecular Mechanisms of Bacterial Pathogenicity  

NASA Astrophysics Data System (ADS)

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.

Fuchs, Thilo Martin

259

Pathogenic properties of Edwardsiella species.  

PubMed Central

The pathogenic characteristics of 35 Edwardsiella strains from clinical and environmental sources were investigated. Overall, most Edwardsiella tarda strains were invasive in HEp-2 cell monolayers, produced a cell-associated hemolysin and siderophores, and bound Congo red; many strains also expressed mannose-resistant hemagglutination against guinea pig erythrocytes. Edwardsiella hoshinae strains bound Congo red and were variable in their invasive and hemolytic capabilities while Edwardsiella ictaluri strains did not produce either factor; neither E. hoshinae nor E. ictaluri expressed mannose-resistant hemagglutination nor elaborated siderophores under the tested conditions. Selected strains of each species tested for mouse lethality indicated strain variability in pathogenic potential, with E. tarda strains being the most virulent; 50% lethal doses in individual strains did not correlate with plasmid content, chemotactic motility, serum resistance, or expression of selected enzyme activities. The results suggest some potential important differences in pathogenic properties that may help explain their environmental distribution and ability to cause disease in humans. Images PMID:1774326

Janda, J M; Abbott, S L; Kroske-Bystrom, S; Cheung, W K; Powers, C; Kokka, R P; Tamura, K

1991-01-01

260

Fructooligosacharides Reduce Pseudomonas aeruginosa PAO1 Pathogenicity through Distinct Mechanisms  

PubMed Central

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

Ortega-Gonzlez, Mercedes; Snchez de Medina, Fermn; Molina-Santiago, Carlos; Lpez-Posadas, Roco; Pacheco, Daniel; Krell, Tino; Martnez-Augustin, Olga; Abdelali, Daddaoua

2014-01-01

261

Pathways of fear and anxiety in dentistry: A review  

PubMed Central

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

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

2014-01-01

262

The chemical arsenal of Burkholderia pseudomallei is essential for pathogenicity.  

PubMed

Increasing evidence has shown that small-molecule chemistry in microbes (i.e., secondary metabolism) can modulate the microbe-host response in infection and pathogenicity. The bacterial disease melioidosis is conferred by the highly virulent, antibiotic-resistant pathogen Burkholderia pseudomallei (BP). Whereas some macromolecular structures have been shown to influence BP virulence (e.g., secretion systems, cellular capsule, pili), the role of the large cryptic secondary metabolome encoded within its genome has been largely unexplored for its importance to virulence. Herein we demonstrate that BP-encoded small-molecule biosynthesis is indispensible for in vivo BP pathogenicity. Promoter exchange experiments were used to induce high-level molecule production from two gene clusters (MPN and SYR) found to be essential for in vivo virulence. NMR structural characterization of these metabolites identified a new class of lipopeptide biosurfactants/biofilm modulators (the malleipeptins) and syrbactin-type proteasome inhibitors, both of which represent overlooked small-molecule virulence factors for BP. Disruption of Burkholderia virulence by inhibiting the biosynthesis of these small-molecule biosynthetic pathways may prove to be an effective strategy for developing novel melioidosis-specific therapeutics. PMID:24884988

Biggins, John B; Kang, Hahk-Soo; Ternei, Melinda A; DeShazer, David; Brady, Sean F

2014-07-01

263

Pathogenic Ubqln2 gains toxic properties to induce neuron death.  

PubMed

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 130days. 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 300days. 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

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

2015-03-01

264

Switch Region for Pathogenic Structural Change in Conformational Disease and Its Prediction  

PubMed Central

Many diseases are believed to be related to abnormal protein folding. In the first step of such pathogenic structural changes, misfolding occurs in regions important for the stability of the native structure. This destabilizes the normal protein conformation, while exposing the previously hidden aggregation-prone regions, leading to subsequent errors in the folding pathway. Sites involved in this first stage can be deemed switch regions of the protein, and can represent perfect binding targets for drugs to block the abnormal folding pathway and prevent pathogenic conformational changes. In this study, a prediction algorithm for the switch regions responsible for the start of pathogenic structural changes is introduced. With an accuracy of 94%, this algorithm can successfully find short segments covering sites significant in triggering conformational diseases (CDs) and is the first that can predict switch regions for various CDs. To illustrate its effectiveness in dealing with urgent public health problems, the reason of the increased pathogenicity of H5N1 influenza virus is analyzed; the mechanisms of the pandemic swine-origin 2009 A(H1N1) influenza virus in overcoming species barriers and in infecting large number of potential patients are also suggested. It is shown that the algorithm is a potential tool useful in the study of the pathology of CDs because: (1) it can identify the origin of pathogenic structural conversion with high sensitivity and specificity, and (2) it provides an ideal target for clinical treatment. PMID:20111584

Liu, Xin; Zhao, Ya-Pu

2010-01-01

265

Alternative pathway evaluation.  

PubMed

The alternative pathway of complement shares its terminal components (C3 and C5 through 9) with the classical pathway, but has several unique components, including factors D, B, and P (properdin). This unit presents methods for assaying total alternative pathway activity and the activity of factors B and D. Radial immunodiffusion (RID) can also be used to measure factor D, B, and P concentrations. PMID:18432715

Giclas, P C

2001-05-01

266

Fluorene Degradation Pathway Map  

NSDL National Science Digital Library

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.

Feng, Jingfeng.

267

Contamination of water resources by pathogenic bacteria  

PubMed Central

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

2014-01-01

268

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

PubMed

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

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

2014-08-19

269

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

PubMed Central

The intestinal mucosa plays a critical role in the hosts 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

Villena, Julio; Kitazawa, Haruki

2014-01-01

270

Regulation of tradeoffs between plant defenses against pathogens with different lifestyles  

PubMed Central

Plants activate distinct defense responses depending on the lifestyle of the attacker encountered. In these responses, salicylic acid (SA) and jasmonic acid (JA) play important signaling roles. SA induces defense against biotrophic pathogens that feed and reproduce on live host cells, whereas JA activates defense against necrotrophic pathogens that kill host cells for nutrition and reproduction. Cross-talk between these defense signaling pathways has been shown to optimize the response against a single attacker. However, its role in defense against multiple pathogens with distinct lifestyles is unknown. Here we show that infection with biotrophic Pseudomonas syringae, which induces SA-mediated defense, rendered plants more susceptible to the necrotrophic pathogen Alternaria brassicicola by suppression of the JA signaling pathway. This process was partly dependent on the cross-talk modulator NPR1. Surprisingly, this tradeoff was restricted to tissues adjacent to the site of initial infection; A. brassicicola infection in systemic tissue was not affected. Even more surprisingly, tradeoff occurred only with the virulent Pseudomonas strain. Avirulent strains that induced programmed cell death (PCD), an effective plant-resistance mechanism against biotrophs, did not cause suppression of JA-dependent defense. This result might be advantageous to the plant by preventing necrotrophic pathogen growth in tissues undergoing PCD. Our findings show that plants tightly control cross-talk between SA- and JA-dependent defenses in a previously unrecognized spatial and pathogen type-specific fashion. This process allows them to prevent unfavorable signal interactions and maximize their ability to concomitantly fend off multiple pathogens. PMID:17998535

Spoel, Steven H.; Johnson, Jessica S.; Dong, Xinnian

2007-01-01

271

The Genus Aeromonas: Taxonomy, Pathogenicity, and Infection  

PubMed Central

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

Janda, J. Michael; Abbott, Sharon L.

2010-01-01

272

The intrinsic resistome of bacterial pathogens  

PubMed Central

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

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

2013-01-01

273

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

PubMed

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

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

2014-11-01

274

Forest Ecosystem Responses to Exotic Pests and Pathogens in Eastern North America  

NSDL National Science Digital Library

This peer-reviewed article from BioScience investigates exotic pests and pathogens in eastern North America.The forests of eastern North America have been subjected to repeated introductions of exotic insect pests and pathogens over the last century, and several new pests are currently invading, or threatening to invade, the region. These pests and pathogens can have major short- and long-term impacts on forest ecosystem processes such as productivity, nutrient cycling, and support of consumer food webs. We identify six key features of the biology of exotic animal pests and the ecology of their hosts that are critical to predicting the general nature and severity of those impacts. Using three examples of introduced pests and pathogens in eastern forest ecosystems, we provide a conceptual framework for assessing potential ecosystem-scale effects.

GARY M. LOVETT, CHARLES D. CANHAM, MARY A. ARTHUR, KATHLEEN C. WEATHERS, and ROSS D. FITZHUGH (;)

2006-05-01

275

Insect antiviral innate immunity: pathways, effectors, and connections  

PubMed Central

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

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

2014-01-01

276

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

PubMed

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 small, interfering RNA pathway that responds through the detection of virus-derived double-stranded RNA to suppress virus replication. However, other innate antimicrobial pathways such as Imd, Toll, and 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

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

2013-12-13

277

Activation of the TLR3 pathway regulates IFN ? production in chickens  

Microsoft Academic Search

Toll-like receptors (TLRs) play key roles in the response to pathogens and in mammals the host response to virus critically relies on TLR3 to detect viral-derived dsRNA. However, in chickens there is a paucity of information about this pathway, and in view of the recent concerns with regard to highly pathogenic avian influenza, there is a clear need for understanding

Adam J. Karpala; John W. Lowenthal; Andrew G. Bean

2008-01-01

278

Rat Somatosensory Cerebropontocerebellar Pathways  

E-print Network

of the largest pathways in the mammalian brain (Tomasch, 1968, 1969). This pathway, which originates from large. After injecting anterograde axonal tracers into electrophysiologically defined parts of the SI, three parts of the cerebral cortex, reaches almost all regions of the cerebellum (for reviews, see rodal

De Schutter, Erik

279

Pathways with Friends  

NSDL National Science Digital Library

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).

Davies, Christian; Egan, Barbara; Hoelscher, Mary; Kuka, Chris; Malone, Molly; Starr, Harmony

2008-01-01

280

The Autonomous Pathogen Detection System  

SciTech Connect

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.

Dzenitis, J M; Makarewicz, A J

2009-01-13

281

Crystallization Pathways in Biomineralization  

NASA Astrophysics Data System (ADS)

A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

Weiner, Steve; Addadi, Lia

2011-08-01

282

Targeting the PI3-kinase/Akt/mTOR Signaling Pathway  

PubMed Central

Synopsis This article presents an overview of the PI3K/Akt/mTOR signaling pathway. As a central regulator of cell growth, protein translation, survival, and metabolism, activation of this signaling pathway contributes to the pathogenesis of many tumor types. Biochemical and genetic aberrations of this pathway observed in various cancer types will be explored. Lastly, pathway inhibitors both in development and already FDA-approved will be discussed. PMID:24012393

Hassan, Burhan; Akcakanat, Argun; Holder, Ashley M.; Meric-Bernstam, Funda

2013-01-01

283

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

PubMed Central

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

Muraille, Eric; Leo, Oberdan; Moser, Muriel

2014-01-01

284

Raphanusanin-mediated resistance to pathogens is light dependent in radish and Arabidopsis thaliana.  

PubMed

Raphanusanin (Ra) is a light-induced inhibitor of hypocotyl growth that responds to unilateral blue light illumination in radish seedlings. We have previously shown that Ra regulates genes that are involved in common defense mechanisms. Many genes that are induced by Ra are also positively regulated by early blue light. To extend the understanding of the role of Ra in pathogen defense, we evaluated the effects of Ra on radish and Arabidopsis thaliana (A. thaliana) infected with the necrotrophic pathogen Botrytis cinerea (B. cinerea) and biotrophic pathogen Pseudomonas syringae (P. syringae). Radish and A. thaliana were found to be resistant to both pathogens when treated with Ra, depending on the concentration used. Interestingly, Ra-mediated resistance to P. syringae is dependent on light because Ra-treated seedlings exhibited enhanced susceptibility to P. syringae infection when grown in the dark. In addition to regulating the biotic defense response, Ra inhibited seed germination and root elongation and enhanced the growth of root hairs in the presence of light in radish and A. thaliana. Our data suggest that Ra regulates the expression of a set of genes involved in defense signaling pathways and plays a role in pathogen defense and plant development. Our results show that light may be generally required not only for the accumulation of Ra but also for its activation during the pathogen defense response. PMID:24923677

Moehninsi; Miura, Kenji; Yamada, Kosumi; Shigemori, Hideyuki

2014-09-01

285

The emerging role of photorespiration and non-photorespiratory peroxisomal metabolism in pathogen defence.  

PubMed

Photorespiration represents one of the major highways of primary plant metabolism and is the most prominent example of metabolic cell organelle integration, since the pathway requires the concerted action of plastidial, peroxisomal, mitochondrial and cytosolic enzymes and organellar transport proteins. Oxygenation of ribulose-1,5-bisphosphate by Rubisco leads to the formation of large amounts of 2-phosphoglycolate, which are recycled to 3-phosphoglycerate by the photorespiratory C2 cycle, concomitant with stoichiometric production rates of H2 O2 in peroxisomes. Apart from its significance for agricultural productivity, a secondary function of photorespiration in pathogen defence has emerged only recently. Here, we summarise literature data supporting the crosstalk between photorespiration and pathogen defence and perform a meta-expression analysis of photorespiratory genes during pathogen attack. Moreover, we screened Arabidopsis proteins newly predicted using machine learning methods to be targeted to peroxisomes, the central H2 O2 -producing organelle of photorespiration, for homologues of known pathogen defence proteins and analysed their expression during pathogen infection. The analyses further support the idea that photorespiration and non-photorespiratory peroxisomal metabolism play multi-faceted roles in pathogen defence beyond metabolism of reactive oxygen species. PMID:23506300

Srhagen, K; Laxa, M; Peterhnsel, C; Reumann, S

2013-07-01

286

Botrytis cinerea Manipulates the Antagonistic Effects between Immune Pathways to Promote Disease Development in Tomato[C][W][OA  

PubMed Central

Plants have evolved sophisticated mechanisms to sense and respond to pathogen attacks. Resistance against necrotrophic pathogens generally requires the activation of the jasmonic acid (JA) signaling pathway, whereas the salicylic acid (SA) signaling pathway is mainly activated against biotrophic pathogens. SA can antagonize JA signaling and vice versa. Here, we report that the necrotrophic pathogen Botrytis cinerea exploits this antagonism as a strategy to cause disease development. We show that B. cinerea produces an exopolysaccharide, which acts as an elicitor of the SA pathway. In turn, the SA pathway antagonizes the JA signaling pathway, thereby allowing the fungus to develop its disease in tomato (Solanum lycopersicum). SA-promoted disease development occurs through Nonexpressed Pathogen Related1. We also show that the JA signaling pathway required for tomato resistance against B. cinerea is mediated by the systemin elicitor. These data highlight a new strategy used by B. cinerea to overcome the plants defense system and to spread within the host. PMID:21665999

El Oirdi, Mohamed; El Rahman, Taha Abd; Rigano, Luciano; El Hadrami, Abdelbasset; Rodriguez, Mara Cecilia; Daayf, Fouad; Vojnov, Adrian; Bouarab, Kamal

2011-01-01

287

Translational control by oncogenic signaling pathways.  

PubMed

Messenger RNA (mRNA) translation is highly regulated in cells and plays an integral role in the overall process of gene expression. The initiation phase of translation is considered to be the most rate-limiting and is often targeted by oncogenic signaling pathways to promote global protein synthesis and the selective translation of tumor-promoting mRNAs. Translational control is a crucial component of cancer development as it allows cancer cells to adapt to the altered metabolism that is generally associated with the tumor state. The phosphoinositide 3-kinase (PI3K)/Akt and Ras/mitogen-activated protein kinase (MAPK) pathways are strongly implicated in cancer etiology, and they exert their biological effects by modulating both global and specific mRNA translation. In addition to having respective translational targets, these pathways also impinge on the mechanistic/mammalian target of rapamycin (mTOR), which acts as a critical signaling node linking nutrient sensing to the coordinated regulation of cellular metabolism. mTOR is best known as a central regulator of protein synthesis and has been implicated in an increasing number of pathological conditions, including cancer. In this article, we describe the current knowledge on the roles and regulation of mRNA translation by various oncogenic signaling pathways, as well as the relevance of these molecular mechanisms to human malignancies. This article is part of a Special Issue entitled: Translation and cancer. PMID:25477072

Gao, Beichen; Roux, Philippe P

2014-12-01

288

The role of autophagy in genetic pathways influencing ageing  

Microsoft Academic Search

Autophagy is a conserved cellular degradation pathway for the breakdown of cytosolic macromolecules and organelles. Constitutive\\u000a autophagy has a housekeeping role and is essential for survival, development and metabolic regulation. Autophagy is also responsive\\u000a to stress and can degrade damaged proteins and organelles, oxidized lipids and intracellular pathogens. Defects in the autophagic\\u000a degradation system are linked to disease pathogenesis and

Maria Markaki; Nektarios Tavernarakis

289

The Arabidopsis PEPR pathway couples local and systemic plant immunity.  

PubMed

Recognition of microbial challenges leads to enhanced immunity at both the local and systemic levels. In Arabidopsis, EFR and PEPR1/PEPR2 act as the receptor for the bacterial elongation factor EF-Tu (elf18 epitope) and for the endogenous PROPEP-derived Pep epitopes, respectively. The PEPR pathway has been described to mediate defence signalling following microbial recognition. Here we show that PROPEP2/PROPEP3 induction upon pathogen challenges is robust against jasmonate, salicylate, or ethylene dysfunction. Comparative transcriptome profiling between Pep2- and elf18-treated plants points to co-activation of otherwise antagonistic jasmonate- and salicylate-mediated immune branches as a key output of PEPR signalling. Accordingly, as well as basal defences against hemibiotrophic pathogens, systemic immunity is reduced in pepr1 pepr2 plants. Remarkably, PROPEP2/PROPEP3 induction is essentially restricted to the pathogen challenge sites during pathogen-induced systemic immunity. Localized Pep application activates genetically separable jasmonate and salicylate branches in systemic leaves without significant PROPEP2/PROPEP3 induction. Our results suggest that local PEPR activation provides a critical step in connecting local to systemic immunity by reinforcing separate defence signalling pathways. PMID:24357608

Ross, Annegret; Yamada, Kohji; Hiruma, Kei; Yamashita-Yamada, Misuzu; Lu, Xunli; Takano, Yoshitaka; Tsuda, Kenichi; Saijo, Yusuke

2014-01-01

290

Lantibiotic production by pathogenic microorganisms.  

PubMed

Lantibiotics are ribosomally synthesised, post-translationally modified antimicrobial peptides produced by Gram positive bacteria, many which have broad-ranging antimicrobial activities. Lantibiotics have long been the subject of investigation with a view to their application as food preservatives or chemotherapeutic agents for clinical and veterinary medicine, while the associated biosynthetic machinery has been employed for peptide engineering purposes. However, although many lantibiotics are produced by generally regarded as safe or food-grade bacteria, it is increasingly apparent that a number of Gram positive pathogens, including strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans, Streptococcus uberis and Enterococcus faecalis, also produce these compounds. It is proposed that production of these antimicrobials may provide the associated microorganisms with a competitive advantage when colonizing/infecting a host, thereby enhancing the virulence of the producing strain. Here we review the production of lantibiotics by these pathogens and discuss how their production may contribute to their disease-causing potential. PMID:22708496

Daly, Karen M; Cotter, Paul D; Hill, Colin; Ross, R Paul

2012-09-01

291

Actin-Based Motility of Intracellular Microbial Pathogens  

PubMed Central

A diverse group of intracellular microorganisms, including Listeria monocytogenes, Shigella spp., Rickettsia spp., and vaccinia virus, utilize actin-based motility to move within and spread between mammalian host cells. These organisms have in common a pathogenic life cycle that involves a stage within the cytoplasm of mammalian host cells. Within the cytoplasm of host cells, these organisms activate components of the cellular actin assembly machinery to induce the formation of actin tails on the microbial surface. The assembly of these actin tails provides force that propels the organisms through the cell cytoplasm to the cell periphery or into adjacent cells. Each of these organisms utilizes preexisting mammalian pathways of actin rearrangement to induce its own actin-based motility. Particularly remarkable is that while all of these microbes use the same or overlapping pathways, each intercepts the pathway at a different step. In addition, the microbial molecules involved are each distinctly different from the others. Taken together, these observations suggest that each of these microbes separately and convergently evolved a mechanism to utilize the cellular actin assembly machinery. The current understanding of the molecular mechanisms of microbial actin-based motility is the subject of this review. PMID:11729265

Goldberg, Marcia B.

2001-01-01

292

Quorum sensing and biofilms in the pathogen, Streptococcus pneumoniae.  

PubMed

Bacteria are able to colonize and thrive in a variety of different environments as a biofilm, but only within the last half century new insights have been gained in this complex biosystem. Bacterial biofilms play a major role in human health by forming a defensive barrier against antibacterial chemical therapeutics and other potential pathogens, and in infectious disease when the bacteria invade normally sterile compartments. Quorum sensing is the signaling network for cell-to-cell communication and utilized by bacteria to regulate biofilms and other cellular processes. This review will describe recent advances in quorum sensing and biofilms. Initially, it will focus on Streptococcus pneumoniae biofilm regulation and the involvement of the ComABCDE pathway. As part of this review an original analysis of the genotypic and phenotypic variation of the signaling molecule, ComC and its cognate receptor ComD, firstly within the pneumococcal species and then within the genus Streptococcus will be presented. Additionally, a pathway similar to ComABCDE, the BlpABCSRH that regulates bacteriocin and immunity protein production that inhibit the growth of competing bacteria will be described. This review will then examine a third quorum sensing mechanism in the pneumococcus, the LuxS/AI-2, and present a novel gene and protein sequence comparative analysis that indicates its occurrence is more universal across bacterial genera compared with the Com pathway, with more sequence similarities between bacterial genera that are known to colonize the mucosal epithelium. PMID:25189864

Galante, Joana; Ho, Alfred C-Y; Tingey, Sarah; Charalambous, Bambos M

2015-01-01

293

Secretory pathway of trypanosomatid parasites.  

PubMed

The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs. PMID:11875130

McConville, Malcolm J; Mullin, Kylie A; Ilgoutz, Steven C; Teasdale, Rohan D

2002-03-01

294

A novel approach for differentiating pathogenic and non-pathogenic Leptospira based on molecular fingerprinting.  

PubMed

Leptospirosis is a worldwide, deadly zoonotic disease. Pathogenic Leptospira causes leptospirosis. The rapid and accurate identification of pathogenic and non-pathogenic Leptospira strains is essential for appropriate therapeutic management and timely intervention for infection control. The molecular fingerprint is a simple and rapid alternative tool for microorganisms identification, which is based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In this study, molecular fingerprint was performed to identify pathogenic strains of Leptospira. Phylogenetic analysis based on 16S rRNA gene sequences was used as the reference method. In addition, a label-free technique was used to reveal the different proteins of pathogenic or non-pathogenic Leptospira. A reference database was constructed using 30 Leptospira strains, including 16 pathogenic strains and 14 non-pathogenic strains. Two super reference spectra that were associated with pathogenicity were established. Overall, 33 Leptospira strains were used for validation, and 32 of 33 Leptospira strains could be identified on the species level and all the 33 could be classified as pathogenic or non-pathogenic. The super reference spectra and the major spectra projection (MSP) dendrogram correctly categorized the Leptospira strains into pathogenic and non-pathogenic groups, which was consistent with the 16S rRNA reference methods. Between the pathogenic and non-pathogenic strains, 108 proteins were differentially expressed. molecular fingerprint is an alternative to conventional molecular identification and can rapidly distinguish between pathogenic and non-pathogenic Leptospira strains. Therefore, molecular fingerprint may play an important role in the clinical diagnosis, treatment, surveillance, and tracking of epidemic outbreaks of leptospirosis. PMID:25464365

Xiao, Di; Zhang, Cuicai; Zhang, Huifang; Li, Xiuwen; Jiang, Xiugao; Zhang, Jianzhong

2014-11-20

295

The Akt signaling pathway  

PubMed Central

Studies using cultured melanoma cells and patient tumor biopsies have demonstrated deregulated PI3 kinase-Akt3 pathway activity in ?70% of melanomas. Furthermore, targeting Akt3 and downstream PRAS40 has been shown to inhibit melanoma tumor development in mice. Although these preclinical studies and several other reports using small interfering RNAs and pharmacological agents targeting key members of this pathway have been shown to retard melanoma development, analysis of early Phase I and Phase II clinical trials using pharmacological agents to target this pathway demonstrate the need for (1) selection of patients whose tumors have PI3 kinase-Akt pathway deregulation, (2) further optimization of therapeutic agents for increased potency and reduced toxicity, (3) the identification of additional targets in the same pathway or in other signaling cascades that synergistically inhibit the growth and progression of melanoma, and (4) better methods for targeted delivery of pharmaceutical agents inhibiting this pathway. In this review we discuss key potential targets in PI3K-Akt3 signaling, the status of pharmacological agents targeting these proteins, drugs under clinical development, and strategies to improve the efficacy of therapeutic agents targeting this pathway. PMID:22157148

Madhunapantula, SubbaRao V; Mosca, Paul J

2011-01-01

296

Defining "adequate" pathogen reduction performance for transfused blood components.  

PubMed

Pathogen reduction of labile blood products offers the opportunity to introduce to the blood banking community the same mechanism of protection that is employed for fractionated or pooled plasma products today--blood components that have been treated with methods to inactivate or reduce the infectivity of a variety of organisms that may contaminate donated blood and thus potentially transmit infection via transfusion. Due to the mechanisms of action, the methods employed in the plasma fractionation environment are not directly applicable to labile blood products. This article examines whether the same criteria of performance required for plasma derivatives (i.e., 6 log/mL reduction by multiple orthogonal methods) should be applied to the treatment of labile components and if not what criteria for performance might be sufficient. In conducting this analysis, we have considered what has been learned in the past several decades regarding the dynamics and infectivity of various pathogens and disease transmission by blood products, the introduction and progressive enhancement of testing methods based on serology and nucleic acid testing, and the performance characteristics for pathogen reduction technologies that are available today. PMID:20374558

Goodrich, Raymond P; Custer, Brian; Keil, Shawn; Busch, Michael

2010-08-01

297

ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence  

PubMed Central

The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence. PMID:24335436

Miyazaki, Taiga; Kohno, Shigeru

2014-01-01

298

A Link between Virulence and Homeostatic Responses to Hypoxia during Infection by the Human Fungal Pathogen Cryptococcus neoformans  

Microsoft Academic Search

Fungal pathogens of humans require molecular oxygen for several essential biochemical reactions, yet virtually nothing is known about how they adapt to the relatively hypoxic environment of infected tissues. We isolated mutants defective in growth under hypoxic conditions, but normal for growth in normoxic conditions, in Cryptococcus neoformans, the most common cause of fungal meningitis. Two regulatory pathways were identified:

Cheryl D Chun; Oliver W Liu; Hiten D Madhani

2007-01-01

299

Original article Sortase anchored proteins of Streptococcus uberis  

E-print Network

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

Boyer, Edmond

300

RESEARCH ARTICLE Open Access Klebsiella pneumoniae related community-  

E-print Network

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. Reported prior medication was high (42.5%). Patients' chest radiographs showed pneumonia (61.3% including

Paris-Sud XI, Université de

301

RESEARCH ARTICLE Open Access Comparative analysis of Klebsiella pneumoniae  

E-print Network

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. pneumoniae isolates of the capsular serotype K2 are among the most virulent. In order to identify novel

Paris-Sud XI, Université de

302

The main auxin biosynthesis pathway in Arabidopsis  

PubMed Central

The phytohormone auxin plays critical roles in the regulation of plant growth and development. Indole-3-acetic acid (IAA) has been recognized as the major auxin for more than 70 y. Although several pathways have been proposed, how auxin is synthesized in plants is still unclear. Previous genetic and enzymatic studies demonstrated that both TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA) and YUCCA (YUC) flavin monooxygenase-like proteins are required for biosynthesis of IAA during plant development, but these enzymes were placed in two independent pathways. In this article, we demonstrate that the TAA family produces indole-3-pyruvic acid (IPA) and the YUC family functions in the conversion of IPA to IAA in Arabidopsis (Arabidopsis thaliana) by a quantification method of IPA using liquid chromatographyelectrospray ionizationtandem MS. We further show that YUC protein expressed in Escherichia coli directly converts IPA to IAA. Indole-3-acetaldehyde is probably not a precursor of IAA in the IPA pathway. Our results indicate that YUC proteins catalyze a rate-limiting step of the IPA pathway, which is the main IAA biosynthesis pathway in Arabidopsis. PMID:22025724

Mashiguchi, Kiyoshi; Tanaka, Keita; Sakai, Tatsuya; Sugawara, Satoko; Kawaide, Hiroshi; Natsume, Masahiro; Hanada, Atsushi; Yaeno, Takashi; Shirasu, Ken; Yao, Hong; McSteen, Paula; Zhao, Yunde; Hayashi, Ken-ichiro; Kamiya, Yuji; Kasahara, Hiroyuki

2011-01-01

303

Activation of the jasmonic acid plant defence pathway alters the composition of rhizosphere bacterial communities.  

PubMed

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

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

2013-01-01

304

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

PubMed Central

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

Zhu, Fei; Zhang, Xiaobo

2013-01-01

305

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

PubMed Central

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

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

2013-01-01

306

Capsicum annuum WRKY protein CaWRKY1 is a negative regulator of pathogen defense  

Microsoft Academic Search

Summary Plants respond to pathogens by regulating a network of signaling pathways that fine-tune transcriptional activation of defense-related genes. The aim of this study was to determine the role of Capsicum annuum WRKY zinc finger-domain transcription factor 1 (CaWRKY1) in defense. In previous studies, CaWRKY1 was found to be rapidly induced in C. annuum (chili pepper) leaves by

Sang-Keun Oh; Kwang-Hyun Baek; Jeong Mee Park; So Young Yi; Seung Hun Yu; Sophien Kamoun; Doil Choi

2007-01-01

307

Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens  

PubMed Central

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 pathogens14. 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. difficiles 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

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

308

The Pathway Tools software  

Microsoft Academic Search

Motivation: Bioinformatics requires reusable software tools for creating model-organism databases (MODs). Results: The Pathway Tools is a reusable, production- quality software environment for creating a type of MOD called a Pathway\\/Genome Database (PGDB). A PGDB such as EcoCyc (see http:\\/\\/ecocyc.org) integrates our evolving understanding of the genes, proteins, metabolic network, and genetic network of an organism. This paper provides an

Peter D. Karp; Suzanne M. Paley; Pedro Romero

2002-01-01

309

Probing Pathways Periodically  

NSDL National Science Digital Library

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.

Timothy C. Elston (Chapel Hill;University of North Carolina REV)

2008-10-21

310

Pathogenic Roles for Fungal Melanins  

PubMed Central

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

Jacobson, Eric S.

2000-01-01

311

Growth Requirements of Pathogenic Leptospira  

PubMed Central

Nutritional requirements for growth at 30 C of Leptospira pomona and L. canicola have been determined. Both pathogenic serotypes initially required bovine serum albumin (BSA) for growth in a medium (SM-4) which permitted growth of the water isolate B-16. Requirement for BSA was eliminated by (i) removing much of the apparent toxicity of free fatty acids in Tween 80 on an anion exchange column, (ii) decreasing extended lag periods observed from small inocula by incorporation of pyruvate into the medium, (iii) the addition of acetate to permit full utilization of substrate fatty acids in Tween 80, and (iv) the addition of glycerol to decrease generation times. Physiologic significance of these findings is discussed, and the possibility is suggested that apparent toxicity of fatty acids for leptospires may result from their auto-oxidation products. The resulting protein-free medium (SM-5) permitted the growth of pathogens at 30 C to high cell yields in low inocula. Highly virulent and avirulent strains from the same clone of L. canicola Moulton were used to determine additional growth requirements associated with virulence. As incubation temperatures were increased from 30 C to those of mammalian hosts, virulent cells required biotin at 35 C and higher levels of K+ and Mg2+ at 37 C. Additional Fe2+ eliminated the necessity for removing the toxicity of Tween 80 by anion exchange. Significance of these physiologic studies are discussed in relationship to virulence. The final protein-free medium (SM-6) grew highly virulent L. canicola from tissue to high yields from low inocula at 37 C with no loss in virulence over several transfers. PMID:4716547

Staneck, Joseph L.; Henneberry, Richard C.; Cox, C. D.

1973-01-01

312

Seaweed polysaccharides and derived oligosaccharides stimulate defense responses and protection against pathogens in plants.  

PubMed

Plants interact with the environment by sensing "non-self" molecules called elicitors derived from pathogens or other sources. These molecules bind to specific receptors located in the plasma membrane and trigger defense responses leading to protection against pathogens. In particular, it has been shown that cell wall and storage polysaccharides from green, brown and red seaweeds (marine macroalgae) corresponding to ulvans, alginates, fucans, laminarin and carrageenans can trigger defense responses in plants enhancing protection against pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed polysaccharides also induce protection against viral, fungal and bacterial infections in plants. In particular, most seaweed polysaccharides and derived oligosaccharides trigger an initial oxidative burst at local level and the activation of salicylic (SA), jasmonic acid (JA) and/or ethylene signaling pathways at systemic level. The activation of these signaling pathways leads to an increased expression of genes encoding: (i) Pathogenesis-Related (PR) proteins with antifungal and antibacterial activities; (ii) defense enzymes such as pheylalanine ammonia lyase (PAL) and lipoxygenase (LOX) which determine accumulation of phenylpropanoid compounds (PPCs) and oxylipins with antiviral, antifugal and antibacterial activities and iii) enzymes involved in synthesis of terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus, seaweed polysaccharides and their derived oligosaccharides induced the accumulation of proteins and compounds with antimicrobial activities that determine, at least in part, the enhanced protection against pathogens in plants. PMID:22363237

Vera, Jeannette; Castro, Jorge; Gonzalez, Alberto; Moenne, Alejandra

2011-12-01

313

Seaweed Polysaccharides and Derived Oligosaccharides Stimulate Defense Responses and Protection Against Pathogens in Plants  

PubMed Central

Plants interact with the environment by sensing non-self molecules called elicitors derived from pathogens or other sources. These molecules bind to specific receptors located in the plasma membrane and trigger defense responses leading to protection against pathogens. In particular, it has been shown that cell wall and storage polysaccharides from green, brown and red seaweeds (marine macroalgae) corresponding to ulvans, alginates, fucans, laminarin and carrageenans can trigger defense responses in plants enhancing protection against pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed polysaccharides also induce protection against viral, fungal and bacterial infections in plants. In particular, most seaweed polysaccharides and derived oligosaccharides trigger an initial oxidative burst at local level and the activation of salicylic (SA), jasmonic acid (JA) and/or ethylene signaling pathways at systemic level. The activation of these signaling pathways leads to an increased expression of genes encoding: (i) Pathogenesis-Related (PR) proteins with antifungal and antibacterial activities; (ii) defense enzymes such as pheylalanine ammonia lyase (PAL) and lipoxygenase (LOX) which determine accumulation of phenylpropanoid compounds (PPCs) and oxylipins with antiviral, antifugal and antibacterial activities and iii) enzymes involved in synthesis of terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus, seaweed polysaccharides and their derived oligosaccharides induced the accumulation of proteins and compounds with antimicrobial activities that determine, at least in part, the enhanced protection against pathogens in plants. PMID:22363237

Vera, Jeannette; Castro, Jorge; Gonzalez, Alberto; Moenne, Alejandra

2011-01-01

314

A Nod to disease vectors: mitigation of pathogen sensing by arthropod saliva  

PubMed Central

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

Sakhon, Olivia S.; Severo, Maiara S.; Kotsyfakis, Michail; Pedra, Joao H. F.

2013-01-01

315

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...

316

Host-Pathogen Interactions: Redefining the Basic Concepts of Virulence and Pathogenicity  

Microsoft Academic Search

While preparing to teach the Microbial Pathogenesis grad- uate course at our institution, we found ourselves struggling to find basic definitions of virulence and pathogenicity that incor- porated the contributions of both the host and the pathogen. The generally used definition of a pathogen as a microbe that causes disease in a host (Table 1) seemed inadequate, because some microbes

ARTURO CASADEVALL; LIISE-ANNE PIROFSKI

1999-01-01

317

Plant-pathogen interactions and elevated CO2: morphological changes in favour of pathogens  

Microsoft Academic Search

Crop losses caused by pests and weeds have been estimated at 42% worldwide, with plant pathogens responsible for almost $10 billion worth of damage in the USA in 1994 alone. Elevated carbon dioxide (ECO2) and associated climate change have the potential to accelerate plant pathogen evolution, which may, in turn, affect virulence. Plant- pathogen interactions under increasing CO2 concentrations have

Janice Ann Lake; Ruth Nicola Wade

2009-01-01

318

ETHYLENE RESPONSE FACTOR1 Integrates Signals from Ethylene and Jasmonate Pathways in Plant Defense  

Microsoft Academic Search

Cross-talk between ethylene and jasmonate signaling pathways determines the activation of a set of defense re- sponses against pathogens and herbivores. However, the molecular mechanisms that underlie this cross-talk are poorly understood. Here, we show that ethylene and jasmonate pathways converge in the transcriptional activation of ETHYLENE RESPONSE FACTOR1 (ERF1), which encodes a transcription factor that regulates the expression of

Oscar Lorenzo; Raquel Piqueras; Jose J. Snchez-Serrano; Roberto Solano

2003-01-01

319

Publishing International Counseling Articles  

ERIC Educational Resources Information Center

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

Hohenshil, Thomas H.; Amundson, Norman E.

2011-01-01

320

c-KIT signaling is targeted by pathogenic Yersinia to suppress the host immune response  

PubMed Central

Background The pathogenic Yersinia species exhibit a primarily extracellular lifestyle through manipulation of host signaling pathways that regulate pro-inflammatory gene expression and cytokine release. To identify host genes that are targeted by Yersinia during the infection process, we performed an RNA interference (RNAi) screen based on recovery of host NF-?B-mediated gene activation in response to TNF-? stimulation upon Y. enterocolitica infection. Results We screened shRNAs against 782 genes in the human kinome and 26 heat shock genes, and identified 19 genes that exhibited ?40% relative increase in NF-?B reporter gene activity. The identified genes function in multiple cellular processes including MAP and ERK signaling pathways, ion channel activity, and regulation of cell growth. Pre-treatment with small molecule inhibitors specific for the screen hits c-KIT and CKII recovered NF-?B gene activation and/or pro-inflammatory TNF-? cytokine release in multiple cell types, in response to either Y. enterocolitica or Y. pestis infection. Conclusions We demonstrate that pathogenic Yersinia exploits c-KIT signaling in a T3SS-dependent manner to downregulate expression of transcription factors EGR1 and RelA/p65, and pro-inflammatory cytokines. This study is the first major functional genomics RNAi screen to elucidate virulence mechanisms of a pathogen that is primarily dependent on extracellular-directed immunomodulation of host signaling pathways for suppression of host immunity. PMID:24206648

2013-01-01

321

Vibrio parahaemolyticus cell biology and pathogenicity determinants  

PubMed Central

Vibrio parahaemolyticus is a significant cause of gastroenteritis worldwide. Characterization of this pathogen has revealed a unique repertoire of virulence factors that allow for colonization of the human host and disease. The following describes the known pathogenicity determinants while establishing the need for continued research. PMID:21782964

Broberg, Christopher A.; Calder, Thomas J.; Orth, Kim

2011-01-01

322

Resistance to Bacterial Pathogens in Plants  

E-print Network

with defense signaling. Bacteria overcome the third layer either by modifying or eliminating existing effectors must overcome to access cell nutrients. To breach these barriers, many plant pathogenic bacteria, pathogens must overcome three layers of defense: (1) preformed physical barriers; (2) a cell

Innes, Roger

323

Viroids: petite RNA pathogens with distinguished talents  

Microsoft Academic Search

Viroids are small, circular, single-stranded RNA molecules that cause several infectious plant diseases. Viroids do not encode any pathogen-specific peptides but nonetheless, the subviral pathogens replicate autonomously and spread in the plant by recruiting host proteins via functional motifs encoded in their RNA genome. During the past couple of years, considerable progress has been made towards comprehending how viroids interact

Martin Tabler; Mina Tsagris

2004-01-01

324

Signal perception in plant pathogen defense  

Microsoft Academic Search

Highly sensitive and specific recognition systems for microbial pathogens are essential for disease resistance in plants. Structurally diverse elicitors from various pathogens have been identified and shown to trigger plant defense mechanisms. Elicitor recognition by the plant is assumed to be mediated by receptors. Plant receptors for fungus-derived elicitors appear to reside preferentially in the plasma membrane, whereas viral and

T. Nrnberger

1999-01-01

325

Drug-resistant plasmids from fish pathogens.  

PubMed

The epidemiological surveillance of drug-resistant strains of the fish pathogenic bacteria Vibrio anguillarum and Pasteurella piscicida carrying transferable R plasmids in fish farms is described. The DNA structure of R plasmids, and the drug-resistant determinants of R plasmids from the fish pathogens Aeromonas hydrophila,aeromonas salmonicida, Edwardsiella tarda, V. anguillarum, and P. piscicida are discussed. PMID:3079184

Aoki, T

1988-07-01

326

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...

327

Incidence and Pathogenic Effect of Streptococcus pseudopneumoniae  

PubMed Central

We evaluated the incidence of Streptococcus pseudopneumoniae in clinical isolates by phenotypic methods and DNA-DNA hybridization. The pathogenic role of this organism was investigated with the mouse peritonitis/sepsis model. Our results show a low incidence (1/120 pneumococcal isolates) and a potential pathogenic effect for S. pseudopneumoniae. PMID:16757628

Harf-Monteil, Colette; Granello, Carole; Le Brun, Ccile; Monteil, Henri; Riegel, Philippe

2006-01-01

328

Pathogens' exploitation of the intestinal food web.  

PubMed

Competition for nutrients is a key factor controlling pathogen colonization within the gastrointestinal tract. In this issue, Ferreyra etal. (2014) and Curtis etal. (2014) show that diverse enteric pathogens can exploit a metabolic byproduct from the commensal microbiota, succinate, to enhance their own virulence expression and proliferation. PMID:25498340

Pham N, Tu Anh; Lawley, Trevor D

2014-12-10

329

76 FR 24793 - Highly Pathogenic Avian Influenza  

Federal Register 2010, 2011, 2012, 2013, 2014

...RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant Health Inspection...any subtype of highly pathogenic avian influenza is considered to exist. The interim...vaccinated for certain types of avian influenza, or that have moved through...

2011-05-03

330

Arthropods vector grapevine trunk disease pathogens.  

PubMed

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

Moyo, P; Allsopp, E; Roets, F; Mostert, L; Halleen, F

2014-10-01

331

MicroRNAs: New Regulators of Toll-Like Receptor Signalling Pathways  

PubMed Central

Toll-like receptors (TLRs), a critical family of pattern recognition receptors (PRRs), are responsible for the innate immune responses via signalling pathways to provide effective host defence against pathogen infections. However, TLR-signalling pathways are also likely to stringently regulate tissue maintenance and homeostasis by elaborate modulatory mechanisms. MicroRNAs (miRNAs) have emerged as key regulators and as an essential part of the networks involved in regulating TLR-signalling pathways. In this review, we highlight our understanding of the regulation of miRNA expression profiles by TLR-signalling pathways and the regulation of TLR-signalling pathways by miRNAs. We focus on the roles of miRNAs in regulating TLR-signalling pathways by targeting multiple molecules, including TLRs themselves, their associated signalling proteins and regulatory molecules, and transcription factors and functional cytokines induced by them, at multiple levels. PMID:24772440

He, Xiaobing; Jing, Zhizhong; Cheng, Guofeng

2014-01-01

332

The care pathway: concepts and theories: an introduction  

PubMed Central

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

Schrijvers, Guus; van Hoorn, Arjan; Huiskes, Nicolette

2012-01-01

333

Learning Cellular Sorting Pathways Using Protein Interactions and Sequence Motifs  

PubMed Central

Abstract Proper subcellular localization is critical for proteins to perform their roles in cellular functions. Proteins are transported by different cellular sorting pathways, some of which take a protein through several intermediate locations until reaching its final destination. The pathway a protein is transported through is determined by carrier proteins that bind to specific sequence motifs. In this article, we present a new method that integrates protein interaction and sequence motif data to model how proteins are sorted through these sorting pathways. We use a hidden Markov model (HMM) to represent protein sorting pathways. The model is able to determine intermediate sorting states and to assign carrier proteins and motifs to the sorting pathways. In simulation studies, we show that the method can accurately recover an underlying sorting model. Using data for yeast, we show that our model leads to accurate prediction of subcellular localization. We also show that the pathways learned by our model recover many known sorting pathways and correctly assign proteins to the path they utilize. The learned model identified new pathways and their putative carriers and motifs and these may represent novel protein sorting mechanisms. Supplementary results and software implementation are available from http://murphylab.web.cmu.edu/software/2010_RECOMB_pathways/. PMID:21999284

Lin, Tien-Ho; Bar-Joseph, Ziv

2011-01-01

334

Alveolar macrophages transport pathogens to lung draining lymph nodes.  

PubMed

The first step in inducing pulmonary adaptive immunity to allergens and airborne pathogens is Ag acquisition and transport to the lung draining lymph nodes (dLN). Dendritic cells (DC) sample the airways, and active transfer of Ag to the lung dLN is considered an exclusive property of migratory DC. However, alveolar macrophages (AM) are the first phagocytes to contact inhaled particulate matter. Although having well-defined immunoregulatory capabilities, AM are generally considered as restricted to the alveoli. We show that murine AM constitutively migrate from lung to dLN and that following exposure to Streptococcus pneumoniae, AM rapidly transport bacteria to this site. Thus AM, and not DC, appear responsible for the earliest delivery of these bacteria to secondary lymphoid tissue. The identification of this novel transport pathway has important consequences for our understanding of lung immunity and suggests more widespread roles for macrophages in the transport of Ags to lymphoid organs than previously appreciated. PMID:19620319

Kirby, Alun C; Coles, Mark C; Kaye, Paul M

2009-08-01

335

Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens  

PubMed Central

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

Nan, Yuchen; Nan, Guoxin; Zhang, Yan-Jin

2014-01-01

336

Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals  

PubMed Central

It is now affordable to order clinically interpreted whole genome sequence reports from clinical laboratories. One major component of these reports is derived from the knowledge base of previously identified pathogenic variants, including research articles, locus specific and other databases. While over 150,000 such pathogenic variants have been identified, many of these were originally discovered in small cohort studies of affected individuals, so their applicability to asymptomatic populations is unclear. We analyzed the prevalence of a large set of pathogenic variants from the medical and scientific literature in a large set of asymptomatic individuals (N=1,092) and found 8.5% of these pathogenic variants in at least one individual. In the average individual in the 1000 Genomes Project, previously identified pathogenic variants occur on average 294 times (?= 25.5) in homozygous form and 942 times (? = 68.2) in heterozygous form. We also find that many of these pathogenic variants are frequently occurring: there are 3,744 variants with MAF >= 0.01 (4.6%) and 2,837 variants with MAF >= 0.05 (3.5%). This indicates that many of these variants may be erroneous findings or have lower penetrance than previously expected. PMID:23818451

Cassa, Christopher A.; Tong, Mark Y.; Jordan, Daniel M.

2013-01-01

337

Ras Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans  

PubMed Central

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 pathwaythe Ras pathwayto 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

Inglis, Diane O.

2013-01-01

338

Alginate Production by Plant-Pathogenic Pseudomonads  

PubMed Central

Eighteen plant-pathogenic and three non-plant-pathogenic pseudomonads were tested for the ability to produce alginic acid as an exopolysaccharide in vitro. Alginate production was demonstrated for 10 of 13 fluorescent plant-pathogenic pseudomonads tested with glucose or gluconate as the carbon source, but not for all 5 nonfluorescent plant pathogens and all 3 non-plant pathogens tested. With sucrose as the carbon source, some strains produced alginate while others produced both polyfructan (levan) and alginate. Alginates ranged from <1 to 28% guluronic acid, were acetylated, and had number-average molecular weights of 11.3 103 to 47.1 103. Polyfructans and alginates were not elicitors of the soybean phytoalexin glyceollin when applied to wounded cotyledon surfaces and did not induce prolonged water soaking of soybean leaf tissues. All or most pseudomonads in rRNA-DNA homology group I may be capable of synthesizing alginate as an exopolysaccharide. PMID:16347146

Fett, William F.; Osman, Stanley F.; Fishman, Marshall L.; Siebles, T. S.

1986-01-01

339

Phytophthora parasitica: a model oomycete plant pathogen  

PubMed Central

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

Meng, Yuling; Zhang, Qiang; Ding, Wei; Shan, Weixing

2014-01-01

340

Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum  

SciTech Connect

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 pathogens ability to survive and proliferate.

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

341

Algae as Reservoirs for Coral Pathogens  

PubMed Central

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

Sweet, Michael J.; Bythell, John C.; Nugues, Maggy M.

2013-01-01

342

IgG1 Is Pathogenic in Leishmania mexicana Infection  

PubMed Central

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

Chu, Niansheng; Thomas, Bolaji N.; Patel, Supriya R.; Buxbaum, Laurence U.

2010-01-01

343

Subtilisin-like proteases in plantpathogen recognition and immune priming: a perspective  

PubMed Central

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

Figueiredo, Andreia; Monteiro, Filipa; Sebastiana, Mnica

2014-01-01

344

Terrific Protein Traffic: The Mystery of Effector Protein Delivery by Filamentous Plant Pathogens  

NSDL National Science Digital Library

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.

Ralph Panstruga (Max-Planck Institute for Plant Breeding Research; Department of Plant-Microbe Interactions)

2009-05-08

345

Pathogenic psychrotolerant sporeformers: an emerging challenge for low-temperature storage of minimally processed foods.  

PubMed

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

Markland, Sarah M; Farkas, Daniel F; Kniel, Kalmia E; Hoover, Dallas G

2013-05-01

346

Quantitative Resistance of Potato to Pectobacterium atrosepticum and Phytophthora infestans: Integrating PAMP-Triggered Response and Pathogen Growth  

PubMed Central

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

Krner, Alexander; Hamelin, Galle; Andrivon, Didier; Val, Florence

2011-01-01

347

Quantitative resistance of potato to Pectobacterium atrosepticum and Phytophthora infestans: integrating PAMP-triggered response and pathogen growth.  

PubMed

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

Krner, Alexander; Hamelin, Galle; Andrivon, Didier; Val, Florence

2011-01-01

348

Evolution of Pathogen Specialisation in a Host Metapopulation: Joint Effects of Host and Pathogen Dispersal  

PubMed Central

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

Papax, Julien; Burdon, Jeremy J.; Lannou, Christian; Thrall, Peter H.

2014-01-01

349

Pathogen resistance of transgenic tobacco plants producing caffeine.  

PubMed

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

Kim, Yun-Soo; Sano, Hiroshi

2008-02-01

350

Plant genes involved in harbouring symbiotic rhizobia or pathogenic nematodes.  

PubMed

The establishment and development of plant-microorganism interactions involve impressive transcriptomic reprogramming of target plant genes. The symbiont (Sinorhizobium meliloti) and the root knot-nematode pathogen (Meloidogyne incognita) induce the formation of new root organs, the nodule and the gall, respectively. Using laser-assisted microdissection, we specifically monitored, at the cell level, Medicago gene expression in nodule zone II cells, which are preparing to receive rhizobia, and in gall giant and surrounding cells, which play an essential role in nematode feeding and constitute the typical root swollen structure, respectively. We revealed an important reprogramming of hormone pathways and C1 metabolism in both interactions, which may play key roles in nodule and gall neoformation, rhizobia endocytosis and nematode feeding. Common functions targeted by rhizobia and nematodes were mainly down-regulated, whereas the specificity of the interaction appeared to involve up-regulated genes. Our transcriptomic results provide powerful datasets to unravel the mechanisms involved in the accommodation of rhizobia and root-knot nematodes. Moreover, they raise the question of host specificity and the evolution of plant infection mechanisms by a symbiont and a pathogen. PMID:22360638

Damiani, Isabelle; Baldacci-Cresp, Fabien; Hopkins, Julie; Andrio, Emilie; Balzergue, Sandrine; Lecomte, Philippe; Puppo, Alain; Abad, Pierre; Favery, Bruno; Hrouart, Didier

2012-04-01

351

Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection.  

PubMed

Metazoans identify and eliminate bacterial pathogens in microbe-rich environments such as the intestinal lumen; however, the mechanisms are unclear. Host cells could potentially use intracellular surveillance or stress response programs to detect pathogens that target monitored cellular activities and then initiate innate immune responses. Mitochondrial function is evaluated by monitoring mitochondrial protein import efficiency of the transcription factor ATFS-1, which mediates the mitochondrial unfolded protein response (UPR(mt)). During mitochondrial stress, mitochondrial import is impaired, allowing ATFS-1 to traffic to the nucleus where it mediates a transcriptional response to re-establish mitochondrial homeostasis. Here we examined the role of ATFS-1 in Caenorhabditis elegans during pathogen exposure, because during mitochondrial stress ATFS-1 induced not only mitochondrial protective genes but also innate immune genes that included a secreted lysozyme and anti-microbial peptides. Exposure to the pathogen Pseudomonas aeruginosa caused mitochondrial dysfunction and activation of the UPR(mt). C. elegans lacking atfs-1 were susceptible to P. aeruginosa, whereas hyper-activation of ATFS-1 and the UPR(mt) improved clearance of P. aeruginosa from the intestine and prolonged C. elegans survival in a manner mainly independent of known innate immune pathways. We propose that ATFS-1 import efficiency and the UPR(mt) is a means to detect pathogens that target mitochondria and initiate a protective innate immune response. PMID:25274306

Pellegrino, Mark W; Nargund, Amrita M; Kirienko, Natalia V; Gillis, Reba; Fiorese, Christopher J; Haynes, Cole M

2014-12-18

352

Cgl-SLT2 is required for appressorium formation, sporulation and pathogenicity in Colletotrichum gloeosporioides  

PubMed Central

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

Yong, H.Y.; Bakar, F.D.A.; Illias, R.M.; Mahadi, N.M.; Murad, A.M.A.

2013-01-01

353

Distinctive expansion of potential virulence genes in the genome of the oomycete fish pathogen Saprolegnia parasitica.  

PubMed

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

Jiang, Rays H Y; de Bruijn, Irene; Haas, Brian J; Belmonte, Rodrigo; Lbach, Lars; Christie, James; van den Ackerveken, Guido; Bottin, Arnaud; Bulone, Vincent; Daz-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

354

Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica  

PubMed Central

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

Belmonte, Rodrigo; Lbach, Lars; Christie, James; van den Ackerveken, Guido; Bottin, Arnaud; Bulone, Vincent; Daz-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

355

Early pathogenic care and the development of ADHD-like symptoms.  

PubMed

Early pathogenic care that is characterised by disregard for the child's basic emotional needs can lead to severe global psychosocial and cognitive dysfunction and deviant developmental trajectories of brain maturation. Reactive attachment disorder (RAD) is a developmental disorder associated with early pathogenic care that is characterised by markedly disturbed ways of relating socially in most contexts. In addition to other severe emotional dysfunctions, children suffering from RAD often display a high number of comorbid attention deficit/hyperactivity disorder (ADHD) symptoms such as inattention, impulsivity and hyperactivity. It is not yet clear whether ADHD-like symptoms in children exposed to pathogenic care represent a true comorbidity of ADHD or similarities in behavioural dysfunction with a different neurodevelopmental pathway in terms of a phenocopy. In this review, we summarise the findings on the neurobiological consequences of early pathogenic care. Pathogenic care is considered a form of care by a primary caretaker involving a lack or a loss of expectable care, e.g., by early separation, frequent change in caregivers, institutionalisation or neglect. The reviewed studies suggest that a primary dysfunction of limbic brain circuits after early pathogenic care might lead to an interference by motivational or emotional cues impinging on prefrontal executive functions resulting in behavioural similarities with ADHD. Thus, the complex phenotype observed after early pathogenic care might be best described by a dimensional approach with behavioural and neurobiological similarities to ADHD coinciding to a certain degree as a function of early experience. Based on this evidence, suggestions for the treatment of ADHD-like symptoms in children after adverse early life experiences are provided. PMID:22661337

Dahmen, Brigitte; Ptz, Vanessa; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2012-09-01

356

Pathogenicity and virulence: another view.  

PubMed Central

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

Isenberg, H D

1988-01-01

357

Myocyte Adrenoceptor Signaling Pathways  

NSDL National Science Digital Library

Adrenoceptors (ARs), members of the G proteinâcoupled 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.

Yang Xiang (Stanford Medical Center;Department of Molecular and Cellular Physiology); Brian Kobilka (Stanford Medical Center;Department of Molecular and Cellular Physiology)

2003-06-06

358

343RESEARCH ARTICLE INTRODUCTION  

E-print Network

pathways interact in a network that controls epithelial patterning in Drosophila oogenesis, an established signaling, Br regulates the Dpp pathway in late stages of oogenesis by controlling the expression in the spatial pattern of Dpp signaling. As a result, the late phase of Dpp signaling in oogenesis has a clear

Shvartsman, Stanislav "Stas"

359

Impact of Chemotherapy on Thrombin Generation and on the Protein C Pathway in Breast Cancer Patients  

Microsoft Academic Search

Although thromboembolism is a problematic complication of chemotherapy, the pathogenic mechanisms by which chemotherapeutic agents exert prothrombotic effects in vivo are unclear.The objective of this study was to examine the effects of adjuvant chemotherapy on thrombin generation, the protein C anticoagulant pathway, and microparticle tissue factor (MP TF) activity in 26 breast cancer patients (stages I to III). The patients

Som D. Mukherjee; Laura L. Swystun; Nigel Mackman; Jian-Guo Wang; Gregory Pond; Mark N. Levine; Patricia C. Liaw

2011-01-01

360

Diversity in the protein N-glycosylation pathways among campylobacter species  

Technology Transfer Automated Retrieval System (TEKTRAN)

The foodborne bacterial pathogen, Campylobacter jejuni, possesses an N-linked protein glycosylation (pgl) pathway involved in adding conserved heptasaccharides to asparaginecontaining motifs of >60 proteins, and releasing the same glycan into its periplasm as free oligosaccharides. In this study, co...

361

Induction of Inflammation by West Nile virus Capsid through the Caspase9 Apoptotic Pathway  

Microsoft Academic Search

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paraly- sis or death. We report that the WNV capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway

Joo-Sung Yang; Mathura P. Ramanathan; Karuppiah Muthumani; Andrew Y. Choo; Sung-Ha Jin; Qian-Chun Yu; Daniel S. Hwang; Daniel K. Choo; Mark D. Lee; Kesen Dang; J. Joseph. Kim; David B. Weiner

362

Coordinate Regulation of the Tryptophan Biosynthetic Pathway and Indolic Phytoalexin Accumulation in Arabidopsis  

Microsoft Academic Search

Little is known about the mechanisms that couple regulation of secondary metabolic pathways to the synthesis of pri- mary metabolic precursors. Camalexin, an indolic secondary metabolite, appears to be the major phytoalexin in Arabidopsis. It was previously shown that camalexin accumulation is caused by infection with plant pathogens, by abiotic elicitors, and in spontaneous lesions in the accelerated cell death

Jianmin Zhao; Boyce Thompson

1996-01-01

363

Pathogen webs in collapsing honey bee colonies.  

PubMed

Recent losses in honey bee colonies are unusual in their severity, geographical distribution, and, in some cases, failure to present recognized characteristics of known disease. Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens. Here we explore the incidence and abundance of currently known honey bee pathogens in colonies suffering from Colony Collapse Disorder (CCD), otherwise weak colonies, and strong colonies from across the United States. Although pathogen identities differed between the eastern and western United States, there was a greater incidence and abundance of pathogens in CCD colonies. Pathogen loads were highly covariant in CCD but not control hives, suggesting that CCD colonies rapidly become susceptible to a diverse set of pathogens, or that co-infections can act synergistically to produce the rapid depletion of workers that characterizes the disorder. We also tested workers from a CCD-free apiary to confirm that significant positive correlations among pathogen loads can develop at the level of individual bees and not merely as a secondary effect of CCD. This observation and other recent data highlight pathogen interactions as important components of bee disease. Finally, we used deep RNA sequencing to further characterize microbial diversity in CCD and non-CCD hives. We identified novel strains of the recently described Lake Sinai viruses (LSV) and found evidence of a shift in gut bacterial composition that may be a biomarker of CCD. The results are discussed with respect to host-parasite interactions and other environmental stressors of honey bees. PMID:22927991

Cornman, R Scott; Tarpy, David R; Chen, Yanping; Jeffreys, Lacey; Lopez, Dawn; Pettis, Jeffery S; vanEngelsdorp, Dennis; Evans, Jay D

2012-01-01

364

Common themes in microbial pathogenicity revisited.  

PubMed Central

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics. PMID:9184008

Finlay, B B; Falkow, S

1997-01-01

365

Pathogen Webs in Collapsing Honey Bee Colonies  

PubMed Central

Recent losses in honey bee colonies are unusual in their severity, geographical distribution, and, in some cases, failure to present recognized characteristics of known disease. Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens. Here we explore the incidence and abundance of currently known honey bee pathogens in colonies suffering from Colony Collapse Disorder (CCD), otherwise weak colonies, and strong colonies from across the United States. Although pathogen identities differed between the eastern and western United States, there was a greater incidence and abundance of pathogens in CCD colonies. Pathogen loads were highly covariant in CCD but not control hives, suggesting that CCD colonies rapidly become susceptible to a diverse set of pathogens, or that co-infections can act synergistically to produce the rapid depletion of workers that characterizes the disorder. We also tested workers from a CCD-free apiary to confirm that significant positive correlations among pathogen loads can develop at the level of individual bees and not merely as a secondary effect of CCD. This observation and other recent data highlight pathogen interactions as important components of bee disease. Finally, we used deep RNA sequencing to further characterize microbial diversity in CCD and non-CCD hives. We identified novel strains of the recently described Lake Sinai viruses (LSV) and found evidence of a shift in gut bacterial composition that may be a biomarker of CCD. The results are discussed with respect to host-parasite interactions and other environmental stressors of honey bees. PMID:22927991

Cornman, R. Scott; Tarpy, David R.; Chen, Yanping; Jeffreys, Lacey; Lopez, Dawn; Pettis, Jeffery S.; vanEngelsdorp, Dennis; Evans, Jay D.

2012-01-01

366

Melanin biosynthesis pathway in Agaricus bisporus mushrooms.  

PubMed

With the full genome sequence of Agaricus bisporus available, it was possible to investigate the genes involved in the melanin biosynthesis pathway of button mushrooms. Based on different BLAST and alignments, genes were identified in the genome which are postulated to be involved in this pathway. Seven housekeeping genes were tested of which 18S rRNA was the only housekeeping gene that was stably expressed in various tissues of different developmental stages. Gene expression was determined for most gene homologs (26 genes) involved in the melanin pathway. Of the analysed genes, those encoding polyphenol oxidase (PPO), the PPO co-factor L-chain (unique for A. bisporus), and a putative transcription factor (photoregulator B) were among the highest expressed in skin tissue. An in depth look was taken at the clustering of several PPO genes and the PPO co-factor gene on chromosome 5, which showed that almost 25% of the protein encoding genes in this cluster have a conserved NACHT and WD40 domain or a P-loop nucleoside triphosphate hydrolase. This article will be the start for an in depth study of the melanin pathway and its role in quality losses of this economically important product. PMID:23123422

Weijn, A; Bastiaan-Net, S; Wichers, H J; Mes, J J

2013-06-01

367

Microfluidic Systems for Pathogen Sensing: A Review  

PubMed Central

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

Mairhofer, Jrgen; Roppert, Kriemhilt; Ertl, Peter

2009-01-01

368

Threats and opportunities of plant pathogenic bacteria.  

PubMed

Plant pathogenic bacteria can have devastating effects on plant productivity and yield. Nevertheless, because these often soil-dwelling bacteria have evolved to interact with eukaryotes, they generally exhibit a strong adaptivity, a versatile metabolism, and ingenious mechanisms tailored to modify the development of their hosts. Consequently, besides being a threat for agricultural practices, phytopathogens may also represent opportunities for plant production or be useful for specific biotechnological applications. Here, we illustrate this idea by reviewing the pathogenic strategies and the (potential) uses of five very different (hemi)biotrophic plant pathogenic bacteria: Agrobacterium tumefaciens, A. rhizogenes, Rhodococcus fascians, scab-inducing Streptomyces spp., and Pseudomonas syringae. PMID:24216222

Tarkowski, Petr; Vereecke, Danny

2014-01-01

369

Articles About Reflexology  

NSDL National Science Digital Library

This collection of articles, provided by Positive Health Magazine, provides information on reflexology for stroke; vertical reflexology; precision reflexology; reflexology for skin disorders; and integrating color with reflexology. The collection of articles also offers some case studies in reflexology. Most of the articles are lengthy and provide helpful color illustrations. The articles would be of interest to aspiring and practicing reflexologists, as well as massage therapists and other practitioners of therapeutic massage.

370

Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria  

PubMed Central

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.

Bravo-Patio, Alejandro; Baizabal-Aguirre, Vctor M.

2014-01-01

371

A Pathway Idea for Model Building  

PubMed Central

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 Lvy 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

Mathai, A.M.; Moschopoulos, Panagis

2013-01-01

372

Pathways to School Success  

ERIC Educational Resources Information Center

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

University of Pittsburgh Office of Child Development, 2012

2012-01-01

373

Environmental Science: Sample Pathway  

E-print Network

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

Goldberg, Bennett

374

PATHOGEN EQUIVALENCY COMMITTEE UPDATE: PFRP EQUIVALENCY DETERMINATIONS  

EPA Science Inventory

This presentation will: Review the mandate of the Pathogen Equivalency Committee Review the PEC's current membership of 10 Discuss how a typical application is evaluated Note where information can be found List present deliberations/applications and describe t...

375

Phytophthora infestans: populations, pathogenicity and phenylamides.  

PubMed

Isolates of Phytophthora infestans (Mont) de Bary (the potato and tomato late blight pathogen) resistant to phenylamides appeared in Europe and North America in the late 1970s and early 1990s respectively. Concurrent, but coincidentally, with both these events there were radical structural shifts in the pathogen populations as immigrant genotypes from Mexico displaced the indigenous populations. Both A1 and A2 mating type isolates are now present in blighted crops, permitting alternative inoculum via germinating sexually produced oospores to influence dynamics of late blight populations. Studies of inheritance of ploidy, host-specific pathogenicity, mating type and resistance to antibiotics and phenylamide fungicides have provided insight into mechanisms of variation in this potent pathogen. PMID:12233186

Shattock, Richard C

2002-09-01

376

Ecological Database of the World's Insect Pathogens  

NSDL National Science Digital Library

A search enabled relational database focusing on pathogens of insects including non-viral, viral, and nematodes, for purposes of insect control. This page does not include information about Bacillus thuringiensis (Bt). (shows 2002 as last update)

0000-00-00

377

Genetic variation in Drosophila melanogaster pathogen susceptibility  

PubMed Central

SUMMARY Genetic variation in susceptibility to pathogens is a central concern both to evolutionary and medical biologists, and for the implementation of biological control programmes. We have investigated the extent of such variation in Drosophila melanogaster, a major model organism for immunological research. We found that within populations, different Drosophila genotypes show wide-ranging variation in their ability to survive infection with the entomopathogenic fungus Beauveria bassiana. Furthermore, striking divergence in susceptibility has occurred between genotypes from temperate and tropical African locations. We hypothesize that this may have been driven by adaptation to local differences in pathogen exposure or host ecology. Genetic variation within populations may be maintained by temporal or spatial variation in the costs and benefits of pathogen defence. Insect pathogens are employed widely as biological control agents and entomopathogenic fungi are currently being developed for reducing malaria transmission by mosquitoes. Our data highlight the need for concern about resistance evolution to these novel biopesticides in vector populations. PMID:16497252

TINSLEY, M. C.; BLANFORD, S.; JIGGINS, F. M.

2007-01-01

378

Aquatic eutrophication promotes pathogenic infection in amphibians  

E-print Network

Aquatic eutrophication promotes pathogenic infection in amphibians Pieter T. J. Johnson* , Jonathan Ribeiroia ondatrae sequentially infects birds, snails, and amphibian larvae, frequently causing severe limb of snail hosts, and, ultimately, the intensity of infection in amphibians. Infection also negatively

Johnson, Pieter

379

Exposure Control--OSHA's Bloodborne Pathogens Standard.  

ERIC Educational Resources Information Center

Explains schools' responsibilities in complying with the Occupational Safety and Health Administration's (OSHA) Bloodborne Pathogens Standard. Describes exposure determination plan, protective equipment, housekeeping practices, labeling of waste, training employees, hepatitis B vaccinations, postexposure evaluation and medical follow-up, and

Granville, Mark F.

1993-01-01

380

Jasmonate Signaling Pathway  

NSDL National Science Digital Library

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.

Robin Liechti (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV); Aurelie Gfeller (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV); Edward E. Farmer (University of Lausanne;Gene Expression Laboratory and Faculty of Biology and Medicine REV)

2006-02-14

381

Pathway-based classification of cancer subtypes  

PubMed Central

Background Molecular markers based on gene expression profiles have been used in experimental and clinical settings to distinguish cancerous tumors in stage, grade, survival time, metastasis, and drug sensitivity. However, most significant gene markers are unstable (not reproducible) among data sets. We introduce a standardized method for representing cancer markers as 2-level hierarchical feature vectors, with a basic gene level as well as a second level of (more stable) pathway markers, for the purpose of discriminating cancer subtypes. This extends standard gene expression arrays with new pathway-level activation features obtained directly from off-the-shelf gene set enrichment algorithms such as GSEA. Such so-called pathway-based expression arrays are significantly more reproducible across datasets. Such reproducibility will be important for clinical usefulness of genomic markers, and augment currently accepted cancer classification protocols. Results The present method produced more stable (reproducible) pathway-based markers for discriminating breast cancer metastasis and ovarian cancer survival time. Between two datasets for breast cancer metastasis, the intersection of standard significant gene biomarkers totaled 7.47% of selected genes, compared to 17.65% using pathway-based markers; the corresponding percentages for ovarian cancer datasets were 20.65% and 33.33% respectively. Three pathways, consisting of Type_1_diabetes mellitus, Cytokine-cytokine_receptor_interaction and Hedgehog_signaling (all previously implicated in cancer), are enriched in both the ovarian long survival and breast non-metastasis groups. In addition, integrating pathway and gene information, we identified five (ID4, ANXA4, CXCL9, MYLK, FBXL7) and six (SQLE, E2F1, PTTG1, TSTA3, BUB1B, MAD2L1) known cancer genes significant for ovarian and breast cancer respectively. Conclusions Standardizing the analysis of genomic data in the process of cancer staging, classification and analysis is important as it has implications for both pre-clinical as well as clinical studies. The paradigm of diagnosis and prediction using pathway-based biomarkers as features can be an important part of the process of biomarker-based cancer analysis, and the resulting canonical (clinically reproducible) biomarkers can be important in standardizing genomic data. We expect that identification of such canonical biomarkers will improve clinical utility of high-throughput datasets for diagnostic and prognostic applications. Reviewers This article was reviewed by John McDonald (nominated by I. King Jordon), Eugene Koonin, Nathan Bowen (nominated by I. King Jordon), and Ekaterina Kotelnikova (nominated by Mikhail Gelfand). PMID:22759382

2012-01-01

382

[Effects of probiotics on pathogenic mycobacteria].  

PubMed

A procedure has been developed to study the antagonistic effect of probitics on pathogenic Mycobacterium tuberculosis, by employing the cultural filtrates obtained after joint incubation of a probiotic and an antagonistic strain in the liquid nutrient medium. It has been shown that two probiotics actively elaborate bactericidal agents that suppress the growth of pathogenic mycobacteria and reduce the number of colony-forming units in the solid egg culture medium by 2-17 times. PMID:17718071

Lazovskaia, A L; Borob'eva, Z G; Slinina, K N; Kul'chitsaia, M A

2007-01-01

383

Perception of conserved pathogen elicitors at the plasma membrane leads to relocalization of the Arabidopsis PEN3 transporter  

PubMed Central

The Arabidopsis PENETRATION RESISTANCE 3 (PEN3) ATP binding cassette transporter participates in nonhost resistance to fungal and oomycete pathogens and is required for full penetration resistance to the barley powdery mildew Blumeria graminis f. sp. hordei. PEN3 resides in the plasma membrane and is recruited to sites of attempted penetration by invading fungal appressoria, where the transporter shows strong focal accumulation. We report that recruitment of PEN3 to sites of pathogen detection is triggered by perception of pathogen-associated molecular patterns, such as flagellin and chitin. PEN3 recruitment requires the corresponding pattern recognition receptors but does not require the BAK1 coreceptor. Pathogen- and pathogen-associated molecular pattern-induced focal accumulation of PEN3 and the PENETRATION RESISTANCE 1 (PEN1) syntaxin show differential sensitivity to specific pharmacological inhibitors, indicating distinct mechanisms for recruitment of these defense-associated proteins to the hostpathogen interface. Focal accumulation of PEN3 requires actin but is not affected by inhibitors of microtubule polymerization, secretory trafficking, or protein synthesis, and plasmolysis experiments indicate that accumulation of PEN3 occurs outside of the plasma membrane within papillae. Our results implicate pattern recognition receptors in the recruitment of defense-related proteins to sites of pathogen detection. Additionally, the process through which PEN3 is recruited to the hostpathogen interface is independent of new protein synthesis and BFA-sensitive secretory trafficking events, suggesting that existing PEN3 is redirected through an unknown trafficking pathway to sites of pathogen detection for export into papillae. PMID:23836668

Underwood, William; Somerville, Shauna C.

2013-01-01

384

Single-molecule nanocatalysis reveals heterogeneous reaction pathways and  

E-print Network

- state accumulation of redox reactions catalysed by single Au nanocrystals19 . Here, we study the realARTICLES Single-molecule nanocatalysis reveals heterogeneous reaction pathways and catalytic in ensemble measurements. Using a single-nanoparticle single-turnover approach, we study the redox catalysis

Chen, Peng

385

Exploring the Ubiquitin-Proteasome Protein Degradation Pathway in Yeast  

ERIC Educational Resources Information Center

This article describes an undergraduate biochemistry laboratory investigating the ubiquitin-proteasome pathway in yeast. In this exercise, the enzyme beta-galactosidase (beta-gal) is expressed in yeast under the control of a stress response promoter. Following exposure to heat stress to induce beta-gal expression, cycloheximide is added to halt

Will, Tamara J.; McWatters, Melissa K.; McQuade, Kristi L.

2006-01-01

386

Pathways to STEMM Professions for Students from Noncollege Homes  

ERIC Educational Resources Information Center

In this article we use data from the Longitudinal Study of American Youth to examine the influence of parent education on pathways to science, technology, engineering, mathematics, and medicine (STEMM) professions. Building on a general model of factors related to STEMM education and employment, we employ a two-group structural equation model to

Miller, Jon D.; Pearson, Willie, Jr.

2012-01-01

387

Using Drosophila melanogaster to map human cancer pathways  

Microsoft Academic Search

The development of human cancer is a multistep process, involving the cooperation of mutations in signalling, cell-cycle and cell-death pathways, as well as interactions between the tumour and the tumour microenvironment. To dissect the steps of tumorigenesis, simple animal models are needed. This article discusses the use of the genetically amenable, multicellular organism, the vinegar fly Drosophila melanogaster. In particular,

Anthony M. Brumby; Helena E. Richardson

2005-01-01

388

Pathways to Childlessness and Late-Life Outcomes  

ERIC Educational Resources Information Center

Via a simultaneous analysis of different life course pathways (marital, occupational, and childbearing histories) and different outcomes, this article addresses the question When does childlessness matter in late life and how? Survey data from Amsterdam (N = 661) and Berlin, Germany (N = 516) are used. Lifelong childlessness results in smaller

Dykstra, Pearl A.; Wagner, Michael

2007-01-01

389

Cell Stem Cell Molecular Pathway and Cell State Responsible  

E-print Network

Cell Stem Cell Article Molecular Pathway and Cell State Responsible for Dissociation-Induced Apoptosis in Human Pluripotent Stem Cells Masatoshi Ohgushi,1,2 Michiru Matsumura,1,2 Mototsugu Eiraku,1 Sasai1,2,* 1Organogenesis and Neurogenesis Group 2Division of Human Stem Cell Technology 3Laboratory

South Bohemia, University of

390

Spontaneous Neurotransmission: An Independent Pathway for Neuronal Signaling?  

NSDL National Science Digital Library

Recent findings suggest that spontaneous neurotransmission is a bona fide pathway for interneuronal signaling that operates independent of evoked transmission via distinct presynaptic as well as postsynaptic substrates. This article will examine the role of spontaneous release events in neuronal signaling by focusing on aspects that distinguish this process from evoked neurotransmission, and evaluate the mechanisms that may underlie this segregation.

Ege T. Kavalali (University of Texas, Southwestern Medical Center Departments of Neuroscience and Physiology); ChiHye Chung (University of Texas, Southwestern Medical Center Department of Neuroscience); Mikhail Khvotchev (University of Texas, southwestern Medical Center Department of Neroscience); Jeremy Leitz (University of Texas, Southwestern Medical Center Department of Neroscience); Elena Nosyreva (University of Texas, Southwestern Medical Center Department of Neroscience); Jesica Raingo (University of Texas, Southwestern Medical Center Department of Neroscience)

2011-02-01

391

Proteases Produced by Vibrio cholerae and Other Pathogenic Vibrios: Pathogenic Roles and Expression  

Microsoft Academic Search

\\u000a Pathogenic vibrios produce various pathogenic factors such as enterotoxin, hemolysin, cytotoxin, protease, siderophore, adhesive\\u000a factor, and hemagglutinin. Direct toxic factors such as enterotoxin, hemolysin, and cytotoxin are related to the symptoms,\\u000a whereas siderophore and adhesive factors may cause indirect factors, which play roles in the establishment of the infection.\\u000a The proteases produced by pathogenic vibrios are long recognized to play

Sumio Shinoda

392

Regulation of Host Cell Transcriptional Physiology by the Avian Pneumovirus Provides Key Insights into Host-Pathogen Interactions  

PubMed Central

Infection with a viral pathogen triggers several pathways in the host cell that are crucial to eliminating infection, as well as those that are used by the virus to enhance its replication and virulence. We have here used suppression subtractive hybridization and cDNA microarray analyses to characterize the host transcriptional response in an avian pneumovirus model of infection. The results of our investigations reveal a dynamic host response that includes the regulation of genes with roles in a vast array of cellular functions as well as those that have not been described previously. The results show a considerable upregulation in transcripts representing the interferon-activated family of genes, predicted to play a role in virus replication arrest. The analysis also identified transcripts for proinflammatory leukocyte chemoattractants, adhesion molecules, and complement that were upregulated and may account for the inflammatory pathology that is the hallmark of viral respiratory infection. Interestingly, alterations in the transcription of several genes in the ubiquitin and endosomal protein trafficking pathways were observed, suggesting a role for these pathways in virus maturation and budding. Taken together, the results of our investigations provide key insights into individual genes and pathways that constitute the host cell's response to avian pneumovirus infection, and they have enabled the development of resources and a model of host-pathogen interaction for an important avian respiratory tract pathogen. PMID:12663796

Munir, Shirin; Kapur, Vivek

2003-01-01

393

Genome dynamics in major bacterial pathogens  

PubMed Central

Pathogenic bacteria continuously encounter multiple forms of stress in their hostile environments, which leads to DNA damage. With the new insight into biology offered by genome sequences, the elucidation of the gene content encoding proteins provides clues toward understanding the microbial lifestyle related to habitat and niche. Campylobacter jejuni, Haemophilus influenzae, Helicobacter pylori, Mycobacterium tuberculosis, the pathogenic Neisseria, Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus are major human pathogens causing detrimental morbidity and mortality at a global scale. An algorithm for the clustering of orthologs was established in order to identify whether orthologs of selected genes were present or absent in the genomes of the pathogenic bacteria under study. Based on the known genes for the various functions and their orthologs in selected pathogenic bacteria, an overview of the presence of the different types of genes was created. In this context, we focus on selected processes enabling genome dynamics in these particular pathogens, namely DNA repair, recombination and horizontal gene transfer. An understanding of the precise molecular functions of the enzymes participating in DNA metabolism and their importance in the maintenance of bacterial genome integrity has also, in recent years, indicated a future role for these enzymes as targets for therapeutic intervention. PMID:19396949

Ambur, Ole Herman; Davidsen, Tonje; Frye, Stephan A; Balasingham, Seetha V; Lagesen, Karin; Rognes, Torbjrn; Tnjum, Tone

2009-01-01

394

Adenoid Reservoir for Pathogenic Biofilm Bacteria?  

PubMed Central

Biofilms of pathogenic bacteria are present on the middle ear mucosa of children with chronic otitis media (COM) and may contribute to the persistence of pathogens and the recalcitrance of COM to antibiotic treatment. Controlled studies indicate that adenoidectomy is effective in the treatment of COM, suggesting that the adenoids may act as a reservoir for COM pathogens. To investigate the bacterial community in the adenoid, samples were obtained from 35 children undergoing adenoidectomy for chronic OM or obstructive sleep apnea. We used a novel, culture-independent molecular diagnostic methodology, followed by confocal microscopy, to investigate the in situ distribution and organization of pathogens in the adenoids to determine whether pathogenic bacteria exhibited criteria characteristic of biofilms. The Ibis T5000 Universal Biosensor System was used to interrogate the extent of the microbial diversity within adenoid biopsy specimens. Using a suite of 16 broad-range bacterial primers, we demonstrated that adenoids from both diagnostic groups were colonized with polymicrobial biofilms. Haemophilus influenzae was present in more adenoids from the COM group (P = 0.005), but there was no significant difference between the two patient groups for Streptococcus pneumoniae or Staphylococcus aureus. Fluorescence in situ hybridization, lectin binding, and the use of antibodies specific for host epithelial cells demonstrated that pathogens were aggregated, surrounded by a carbohydrate matrix, and localized on and within the epithelial cell surface, which is consistent with criteria for bacterial biofilms. PMID:21307211

Nistico, L.; Kreft, R.; Gieseke, A.; Coticchia, J. M.; Burrows, A.; Khampang, P.; Liu, Y.; Kerschner, J. E.; Post, J. C.; Lonergan, S.; Sampath, R.; Hu, F. Z.; Ehrlich, G. D.; Stoodley, P.; Hall-Stoodley, L.

2011-01-01

395

Antibody-mediated resistance against plant pathogens.  

PubMed

Plant diseases have a significant impact on the yield and quality of crops. Many strategies have been developed to combat plant diseases, including the transfer of resistance genes to crops by conventional breeding. However, resistance genes can only be introgressed from sexually-compatible species, so breeders need alternative measures to introduce resistance traits from more distant sources. In this context, genetic engineering provides an opportunity to exploit diverse and novel forms of resistance, e.g. the use of recombinant antibodies targeting plant pathogens. Native antibodies, as a part of the vertebrate adaptive immune system, can bind to foreign antigens and eliminate them from the body. The ectopic expression of antibodies in plants can also interfere with pathogen activity to confer disease resistance. With sufficient knowledge of the pathogen life cycle, it is possible to counter any disease by designing expression constructs so that pathogen-specific antibodies accumulate at high levels in appropriate sub-cellular compartments. Although first developed to tackle plant viruses and still used predominantly for this purpose, antibodies have been targeted against a diverse range of pathogens as well as proteins involved in plant-pathogen interactions. Here we comprehensively review the development and implementation of antibody-mediated disease resistance in plants. PMID:21872654

Safarnejad, Mohammad Reza; Jouzani, Gholamreza Salehi; Tabatabaei, Meisam; Tabatabaie, Meisam; Twyman, Richard M; Schillberg, Stefan

2011-01-01

396

The secretory pathway: exploring yeast diversity.  

PubMed

Protein secretion is an essential process for living organisms. In eukaryotes, this encompasses numerous steps mediated by several hundred cellular proteins. The core functions of translocation through the endoplasmic reticulum membrane, primary glycosylation, folding and quality control, and vesicle-mediated secretion are similar from yeasts to higher eukaryotes. However, recent research has revealed significant functional differences between yeasts and mammalian cells, and even among diverse yeast species. This review provides a current overview of the canonical protein secretion pathway in the model yeast Saccharomyces cerevisiae, highlighting differences to mammalian cells as well as currently unresolved questions, and provides a genomic comparison of the S. cerevisiae pathway to seven other yeast species where secretion has been investigated due to their attraction as protein production platforms, or for their relevance as pathogens. The analysis of Candida albicans, Candida glabrata, Kluyveromyces lactis, Pichia pastoris, Hansenula polymorpha, Yarrowia lipolytica, and Schizosaccharomyces pombe reveals that many - but not all - secretion steps are more redundant in S. cerevisiae due to duplicated genes, while some processes are even absent in this model yeast. Recent research obviates that even where homologous genes are present, small differences in protein sequence and/or differences in the regulation of gene expression may lead to quite different protein secretion phenotypes. PMID:23480475

Delic, Marizela; Valli, Minoska; Graf, Alexandra B; Pfeffer, Martin; Mattanovich, Diethard; Gasser, Brigitte

2013-11-01

397

MICROBIOLOGY: A Fifth Pathway of Carbon Fixation  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Genome sequence analyses and enzymatic studies reveal a novel CO2 fixation cycle in some autotrophic archaea. Autotrophs are organisms that can grow using carbon dioxide (CO2) as their sole source of carbon. Four mechanisms are known by which autotrophic organisms fix carbon. Berg et al. describe a fifth autotrophic CO2 fixation pathway in archaea that may have been used by some of the earliest organisms on Earth.

Rudolf K. Thauer (Max Planck Institute for Terrestrial Microbiology;)

2007-12-14

398

Evolutionary Rate Variation in Anthocyanin Pathway Genes Yingqing Lu and Mark D. Rausher  

E-print Network

Evolutionary Rate Variation in Anthocyanin Pathway Genes Yingqing Lu and Mark D. Rausher Department of the anthocyanin pigment pathway have evolved less rapidly than downstream enzymes. In this article we show analysis of rates of anthocyanin structural gene evolution, Rausher, Miller, and Tiffin (1999) demonstrated

Rausher, Mark D.

399

Responding to directional cues: a tale of two cells [biochemical signaling pathways  

Microsoft Academic Search

The study of biochemical signaling pathways is of immense importance. Abnormalities in cell signaling have been linked to the development of many serious diseases. In this article, the author has presented two of the best-understood signaling pathways in eukaryotic cells and illustrated the similarities between traditional control engineering tasks, including step disturbance rejection and amplification. The illustrations have shown how

Saurabh Paliwal; Lan Ma; J. Krishnan; Andre Levchenko; Pablo A. Iglesias

2004-01-01

400

Molecular Cell Short Article  

E-print Network

metabolism or by ionizing radiation and chemotherapeutic drugs. Their repair is critical for the successful pathway are linked to immunodefi- ciency, cancer predisposition, and other diseases. A critical question

Lahav, Galit

401

The 3-Hydroxy-2-Butanone Pathway Is Required for Pectobacterium carotovorum Pathogenesis  

PubMed Central

Pectobacterium species are necrotrophic bacterial pathogens that cause soft rot diseases in potatoes and several other crops worldwide. Gene expression data identified Pectobacterium carotovorum subsp. carotovorum budB, which encodes the ?-acetolactate synthase enzyme in the 2,3-butanediol pathway, as more highly expressed in potato tubers than potato stems. This pathway is of interest because volatiles produced by the 2,3-butanediol pathway have been shown to act as plant growth promoting molecules, insect attractants, and, in other bacterial species, affect virulence and fitness. Disruption of the 2,3-butanediol pathway reduced virulence of P. c. subsp. carotovorum WPP14 on potato tubers and impaired alkalinization of growth medium and potato tubers under anaerobic conditions. Alkalinization of the milieu via this pathway may aid in plant cell maceration since Pectobacterium pectate lyases are most active at alkaline pH. PMID:21876734

Marquez-Villavicencio, Maria del Pilar; Weber, Brooke; Witherell, R. Andrews; Willis, David K.; Charkowski, Amy O.

2011-01-01

402

Pathway and Resource Overview (Presentation)  

SciTech Connect

This presentation provides information about hydrogen pathway analysis, which is analysis of the total levelized cost (including return on investment). Well-to-wheels (WTW) energy use, and WTW emissions for hydrogen production, delivery, and distribution pathways.

Ruth, M. F.

2009-11-16

403

Pathways to Science: STEM  

NSDL National Science Digital Library

Sponsored by NASA and the National Science Foundation, the Pathways to Science Project was created by the Institute for Broadening Participation to support "pathways to the STEM fields: science, technology, engineering, and mathematics." The project works on connecting underrepresented groups with STEM programs, funding, mentoring, and resources. The "Students" area features a sign-in area where students can sign up to receive targeted emails that will inform them of new STEM-focused scholarship and mentoring opportunities. The "Programs" area features a database of over 1500 programs designed for K-8 students, college educators, and undergraduate students. Additionally, the site also includes a "News" area where users can learn about recent success stories from universities around the United States, along with the particulars of upcoming conferences and seminars.

404

Arabidopsis Cytokinin Signaling Pathway  

NSDL National Science Digital Library

Cytokinins are essential plant hormones that control cell division, shoot meristem initiation, leaf and root differentiation, vasculature patterning, chloroplast biogenesis, photomorphogenesis, fertility, seed development, senescence, and stress tolerance. The Arabidopsis cytokinin signal transduction pathway involves hybrid histidine protein kinases [AHK2, AHK3, and AHK4 (also known as CRE1or WOL)] as cytokinin receptors, histidine phosphotransfer proteins (AHPs), and nuclear response regulators (ARRs) that serve as transcriptional regulators. There are four major steps in the cytokinin phosphorelay: (i) AHK sensing and signaling, (ii) AHP nuclear translocation, (iii) ARR-dependent transcriptional activation, and (iv) a negative-feedback loop through cytokinin-inducible ARR gene products. Each step is executed by components encoded by multigene families. The effects of cytokinin depend on cell type, environment, and developmental stage. The response is frequently the outcome of interactions with other plant signaling pathways.

Bruno Muller (Department of Molecular Biology at Massachusetts General Hospital and Department of Genetics at Harvard Medical School; REV)

2007-10-09

405

Pathogenic and Obesogenic Factors Associated with Inflammation in Chinese Children, Adolescents and Adults  

PubMed Central

Objectives Influenced by pathogen exposure and obesity, inflammation provides a critical biological pathway linking changing environments to the development of cardiometabolic disease. This study tests the relative contribution of obesogenic and pathogenic factors to moderate and acute CRP elevations in Chinese children, adolescents and adults. Methods Data come from 8795 participants in the China Health and Nutrition Study. Age-stratified multinomial logistic models were used to test the association between illness history, pathogenic exposures, adiposity, health behaviors and moderate (1-10 mg/L in children and 3-10 mg/L in adults) and acute (>10mg/L) CRP elevations, controlling for age, sex and clustering by household. Backward model selection was used to assess which pathogenic and obesogenic predictors remained independently associated with moderate and acute CRP levels when accounting for simultaneous exposures. Results Overweight was the only significant independent risk factor for moderate inflammation in children (RRR 2.10, 95%CI 1.13-3.89). History of infectious (RRR 1.28, 95%CI 1.08-1.52) and non-communicable (RRR 1.37, 95%CI 1.12-1.69) disease, overweight (RRR 1.66, 95%CI 1.45-1.89) and high waist circumference (RRR 1.63, 95%CI 1.42-1.87) were independently associated with a greater likelihood of moderate inflammation in adults while history of infectious disease (RRR 1.87, 95%CI 1.35-2.56) and overweight (RRR 1.40, 95%CI 1.04-1.88) were independently associated with acute inflammation. Environmental pathogenicity was associated with a reduced likelihood of moderate inflammation, but a greater likelihood of acute inflammation in adults. Conclusions These results highlight the importance of both obesogenic and pathogenic factors in shaping inflammation risk in societies undergoing nutritional and epidemiological transitions. PMID:24123588

Thompson, Amanda L.; Houck, Kelly M.; Adair, Linda; Gordon-Larsen, Penny; Du, Shufa; Zhang, Bing; Popkin, Barry

2014-01-01

406

Dynamic Evolution of Pathogenicity Revealed by Sequencing and Comparative Genomics of 19 Pseudomonas syringae Isolates  

PubMed Central

Closely related pathogens may differ dramatically in host range, but the molecular, genetic, and evolutionary basis for these differences remains unclear. In many Gram- negative bacteria, including the phytopathogen Pseudomonas syringae, type III effectors (TTEs) are essential for pathogenicity, instrumental in structuring host range, and exhibit wide diversity between strains. To capture the dynamic nature of virulence gene repertoires across P. syringae, we screened 11 diverse strains for novel TTE families and coupled this nearly saturating screen with the sequencing and assembly of 14 phylogenetically diverse isolates from a broad collection of diseased host plants. TTE repertoires vary dramatically in size and content across all P. syringae clades; surprisingly few TTEs are conserved and present in all strains. Those that are likely provide basal requirements for pathogenicity. We demonstrate that functional divergence within one conserved locus, hopM1, leads to dramatic differences in pathogenicity, and we demonstrate that phylogenetics-informed mutagenesis can be used to identify functionally critical residues of TTEs. The dynamism of the TTE repertoire is mirrored by diversity in pathways affecting the synthesis of secreted phytotoxins, highlighting the likely role of both types of virulence factors in determination of host range. We used these 14 draft genome sequences, plus five additional genome sequences previously reported, to identify the core genome for P. syringae and we compared this core to that of two closely related non-pathogenic pseudomonad species. These data revealed the recent acquisition of a 1 Mb megaplasmid by a sub-clade of cucumber pathogens. This megaplasmid encodes a type IV secretion system and a diverse set of unknown proteins, which dramatically increases both the genomic content of these strains and the pan-genome of the species. PMID:21799664

Romanchuk, Artur; Chang, Jeff H.; Mukhtar, M. Shahid; Cherkis, Karen; Roach, Jeff; Grant, Sarah R.; Jones, Corbin D.; Dangl, Jeffery L.

2011-01-01

407

TABLE OF CONTENTS ARTICLE PAGE  

E-print Network

OR TECHNOLOGICAL CHANGE ........................ 48 ARTICLE 25- TRANSPORTATION ALLOWANCE ­ JOB POSTINGS................................................................................... 17................................................................................. 49 ARTICLE 27- PROFESSIONAL DEVELOPMENT/ORIENTATION.............................. 51 ARTICLE 28

Abolmaesumi, Purang

408

Classical pathway evaluation.  

PubMed

This unit describes several assay methods that can be used to determine the functional status of the classical pathway of complement and to quantitate its component proteins. The classical pathway includes C1qrs, C2, C4, C3, C5, C6, C7, C8, and C9, listed in the order in which they interact. Two CH(50) assay procedures are presented that test total classical pathway function; one is carried out in test tubes, whereas the alternate protocol describes a variation that is carried out in 96-well microtiter plates. Three support protocols describe preparing serum and erythrocyte-antibody complexes (EA) for use in CH(50) assays,and titrating of hemolysin for use in EA preparation. As an alternative to functional assays, radial immunodiffusion (RID) methods are also presented. These can be used to measure the concentrations of most circulating complement proteins and to evaluate the functional status of C1-esterase inhibitor. A fourth support protocol provides a method to determine antibody concentrations for RID assays. PMID:18432714

Giclas, P C

2001-05-01

409

Article Watch: September 2013  

PubMed Central

This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, GRU-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606; Phone: 706-713-2216; Fax: 706-713-2221; E-mail: cslaught@uga.edu; or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association.

Slaughter, Clive A.

2013-01-01

410

Method of drying articles  

DOEpatents

A method of drying a green particulate article includes the steps of: (a) Providing a green article which includes a particulate material and a pore phase material, the pore phase material including a solvent; and (b) contacting the green article with a liquid desiccant for a period of time sufficient to remove at least a portion of the solvent from the green article, the pore phase material acting as a semipermeable barrier to allow the solvent to be sorbed into the liquid desiccant, the pore phase material substantially preventing the liquid desiccant from entering the pores. 3 figs.

Janney, M.A.; Kiggans, J.O. Jr.

1999-03-23

411

Method of drying articles  

DOEpatents

A method of drying a green particulate article includes the steps of: a. Providing a green article which includes a particulate material and a pore phase material, the pore phase material including a solvent; and b. contacting the green article with a liquid desiccant for a period of time sufficient to remove at least a portion of the solvent from the green article, the pore phase material acting as a semipermeable barrier to allow the solvent to be sorbed into the liquid desiccant, the pore phase material substantially preventing the liquid desiccant from entering the pores.

Janney, Mark A. (Knoxville, TN); Kiggans, Jr., James O. (Oak Ridge, TN)

1999-01-01

412

Infection of zebrafish embryos with intracellular bacterial pathogens.  

PubMed

Zebrafish (Danio rerio) embryos are increasingly used as a model for studying the function of the vertebrate innate immune system in host-pathogen interactions. The major cell types of the innate immune system, macrophages and neutrophils, develop during the first days of embryogenesis prior to the maturation of lymphocytes that are required for adaptive immune responses. The ease of obtaining large numbers of embryos, their accessibility due to external development, the optical transparency of embryonic and larval stages, a wide range of genetic tools, extensive mutant resources and collections of transgenic reporter lines, all add to the versatility of the zebrafish model. Salmonella enterica serovar Typhimurium (S. typhimurium) and Mycobacterium marinum can reside intracellularly in macrophages and are frequently used to study host-pathogen interactions in zebrafish embryos. The infection processes of these two bacterial pathogens are interesting to compare because S. typhimurium infection is acute and lethal within one day, whereas M. marinum infection is chronic and can be imaged up to the larval stage. The site of micro-injection of bacteria into the embryo determines whether the infection will rapidly become systemic or will initially remain localized. A rapid systemic infection can be established by micro-injecting bacteria directly into the blood circulation via the caudal vein at the posterior blood island or via the Duct of Cuvier, a wide circulation channel on the yolk sac connecting the heart to the trunk vasculature. At 1 dpf, when embryos at this stage have phagocytically active macrophages but neutrophils have not yet matured, injecting into the blood island is preferred. For injections at 2-3 dpf, when embryos also have developed functional (myeloperoxidase-producing) neutrophils, the Duct of Cuvier is preferred as the injection site. To study directed migration of myeloid cells towards local infections, bacteria can be injected into the tail muscle, otic vesicle, or hindbrain ventricle. In addition, the notochord, a structure that appears to be normally inaccessible to myeloid cells, is highly susceptible to local infection. A useful alternative for high-throughput applications is the injection of bacteria into the yolk of embryos within the first hours after fertilization. Combining fluorescent bacteria and transgenic zebrafish lines with fluorescent macrophages or neutrophils creates ideal circumstances for multi-color imaging of host-pathogen interactions. This video article will describe detailed protocols for intravenous and local infection of zebrafish embryos with S. typhimurium or M. marinum bacteria and for subsequent fluorescence imaging of the interaction with cells of the innate immune system. PMID:22453760

Benard, Erica L; van der Sar, Astrid M; Ellett, Felix; Lieschke, Graham J; Spaink, Herman P; Meijer, Annemarie H

2012-01-01

413

Vibrio vulnificusBiotype 2, Pathogenic for Eels, Is Also an Opportunistic Pathogen for Humans  

Microsoft Academic Search

We report that the eel pathogen Vibrio vulnificus biotype 2 is also an opportunistic pathogen for humans. Results from a detailed comparative study using reference strains of both biotypes revealed that the clinical strain ATCC 33817, originally isolated from a human leg wound and classified as V. vulnificus (no reference on its biotype is noted), belongs to biotype 2 of

CARMEN AMARO; ANDELENA G. BIOSCA

414

Pathogenicity of reassortant H5N1 highly pathogenic avian influenza viruses in domestic ducks  

Technology Transfer Automated Retrieval System (TEKTRAN)

The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks has increased over time. These changes in virulence have been reported with viruses from countries with high population of domestic ducks, including Egypt. In order to understand which viral genes are contri...

415

Pathogenicity of two Egyptian H5N1 highly pathogenic avian influenza viruses in domestic ducks  

Technology Transfer Automated Retrieval System (TEKTRAN)

Domestic ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Interestingly, the pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in ducks. These changes in vir...

416

An easy operating pathogen microarray (EOPM) platform for rapid screening of vertebrate pathogens  

PubMed Central

Background Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. Methods An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. Results Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. Conclusions EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control. PMID:24053492

2013-01-01

417

Plant pathogens: how can molecular genetic information on plant pathogens assist in breeding disease resistant crops  

Microsoft Academic Search

Numerous phytopathogenic fungi and Oomycete species cause disease on crop plants. Over the past 17 years a combination of protein purification and forward and reverse genetics has lead to the identification of > 150 distinct pathogenicity and virulence genes required by pathogens to cause disease. Many conserved molecular mechanisms are now recognised that underpin the pathogenesis of very diverse species.

Kim Hammond-Kosack; Martin Urban; Thomas Baldwin; Arsalan Daudi; Jason Rudd; John Keon; John Lucas; Kerry Maguire; Dmitry Kornyukhin; Hai-Chun Jing; Chris Bass; John Antoniw

2004-01-01

418

Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with the insect pathogen Photorhabdus luminescens  

Microsoft Academic Search

BACKGROUND: The Gram-negative bacterium Photorhabdus asymbiotica (Pa) has been recovered from human infections in both North America and Australia. Recently, Pa has been shown to have a nematode vector that can also infect insects, like its sister species the insect pathogen P. luminescens (Pl). To understand the relationship between pathogenicity to insects and humans in Photorhabdus we have sequenced the

Paul Wilkinson; Nicholas R Waterfield; Lisa Crossman; Craig Corton; Maria Sanchez-Contreras; Isabella Vlisidou; Andrew Barron; Alexandra Bignell; Louise Clark; Douglas Ormond; Matthew Mayho; Nathalie Bason; Frances Smith; Mark Simmonds; Carol Churcher; David Harris; Nicholas R Thompson; Michael Quail; Julian Parkhill; Richard H ffrench-Constant

2009-01-01

419

THERMAL INACTIVATION OF FOODBORNE PATHOGENS AND THE USDA PATHOGEN MODELING PROGRAM  

Technology Transfer Automated Retrieval System (TEKTRAN)

The use of heat to inactivate foodborne pathogens is a critical control point and the most common means of assuring the microbiological safety of processed foods. A key to optimization of the heating step is defining the target pathogens' heat resistance. Sufficient evidence exists to document tha...

420

Evolution of a simian immunodeficiency virus pathogen.  

PubMed

Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-kappaB binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3' half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5' half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU. PMID:9420239

Edmonson, P; Murphey-Corb, M; Martin, L N; Delahunty, C; Heeney, J; Kornfeld, H; Donahue, P R; Learn, G H; Hood, L; Mullins, J I

1998-01-01

421

A bacterial pathogen uses dimethylsulfoniopropionate as a cue to target heat-stressed corals.  

PubMed

Diseases are an emerging threat to ocean ecosystems. Coral reefs, in particular, are experiencing a worldwide decline because of disease and bleaching, which have been exacerbated by rising seawater temperatures. Yet, the ecological mechanisms behind most coral diseases remain unidentified. Here, we demonstrate that a coral pathogen, Vibrio coralliilyticus, uses chemotaxis and chemokinesis to target the mucus of its coral host, Pocillopora damicornis. A primary driver of this response is the host metabolite dimethylsulfoniopropionate (DMSP), a key element in the global sulfur cycle and a potent foraging cue throughout the marine food web. Coral mucus is rich in DMSP, and we found that DMSP alone elicits chemotactic responses of comparable intensity to whole mucus. Furthermore, in heat-stressed coral fragments, DMSP concentrations increased fivefold and the pathogen's chemotactic response was correspondingly enhanced. Intriguingly, despite being a rich source of carbon and sulfur, DMSP is not metabolized by the pathogen, suggesting that it is used purely as an infochemical for host location. These results reveal a new role for DMSP in coral disease, demonstrate the importance of chemical signaling and swimming behavior in the recruitment of pathogens to corals and highlight the impact of increased seawater temperatures on disease pathways. PMID:24335830

Garren, Melissa; Son, Kwangmin; Raina, Jean-Baptiste; Rusconi, Roberto; Menolascina, Filippo; Shapiro, Orr H; Tout, Jessica; Bourne, David G; Seymour, Justin R; Stocker, Roman

2014-05-01

422

Host-Directed Antimicrobial Drugs with Broad-Spectrum Efficacy against Intracellular Bacterial Pathogens  

PubMed Central

ABSTRACT We sought a new approach to treating infections by intracellular bacteria, namely, by altering host cell functions that support their growth. We screened a library of 640 Food and Drug Administration (FDA)-approved compounds for agents that render THP-1 cells resistant to infection by four intracellular pathogens. We identified numerous drugs that are not antibiotics but were highly effective in inhibiting intracellular bacterial growth with limited toxicity to host cells. These compounds are likely to target three kinds of host functions: (i) G protein-coupled receptors, (ii) intracellular calcium signals, and (iii) membrane cholesterol distribution. The compounds that targeted G protein receptor signaling and calcium fluxes broadly inhibited Coxiella burnetii, Legionella pneumophila, Brucella abortus, and Rickettsia conorii, while those directed against cholesterol traffic strongly attenuated the intracellular growth of C.burnetii and L.pneumophila. These pathways probably support intracellular pathogen growth so that drugs that perturb them may be therapeutic candidates. Combining host- and pathogen-directed treatments is a strategy to decrease the emergence of drug-resistant intracellular bacterial pathogens. PMID:25073644

Czy?, Daniel M.; Potluri, Lakshmi-Prasad; Jain-Gupta, Neeta; Riley, Sean P.; Martinez, Juan J.; Steck, Theodore L.; Crosson, Sean; Gabay, Jolle E.

2014-01-01

423

Systems approach to characterizing cell signaling in host-pathogen response to staphylococcus toxin.  

SciTech Connect

The mammalian immune system is capable of highly sensitive and specific responses when challenged by pathogens. It is believed that the human immune repertoire - the total number of distinct antigens that can be recognized - is between 10{sup 9} and 10{sup 11}. The most specific responses are cell mediated and involve complex and subtle communications among the immune cells via small proteins known as cytokines. The details of host-pathogen response are exceedingly complex, involving both intracellular and extracellular mechanisms. These include the presentation of antigen by B cells to helper T cells and subsequent stimulation of signal transduction pathways and gene expression within both B and T-cell populations. These in turn lead to the secretion of cytokines and receptor expression. Intercellular cytokine signaling can trigger a host of immune responses including the proliferation and specialization of naive immune cells and the marshaling of effector cells to combat infection. In the ever-evolving game of threat and countermeasure played out by pathogens and their intended hosts, there are direct assaults aimed at subverting the immune system's ability to recognize antigens and respond effectively to challenge by pathogens. Staphylococcus is one of these. Staph bacteria secrete a variety of toxins known generically as superantigens. Superantigen molecules bind simultaneously to the MHC receptors of antigen presenting cells and the TCR receptors of helper T cells, locking them in place and leading to overstimulation. This strategy can effectively burn out the immune system in a matter of days.

Ambrosiano, J. J. (John J.); Gupta, G. (Goutam); Gray, P. C. (Perry C.); Hush, D. R. (Donald R.); Fugate, M. L. (Michael L.); Cleland, T. J. (Timothy J.); Roberts, R. M. (Randy M.); Hlavacek, W. S. (William S.); Smith, J. L. (Jessica L.)

2002-01-01

424

Pathogenic Mechanisms in Type 1 Diabetes: The Islet is Both Target and Driver of Disease  

PubMed Central

Recent advances in our understanding of the pathogenesis of type 1 diabetes have occurred in all steps of the disease. This review outlines the pathogenic mechanisms utilized by the immune system to mediate destruction of the pancreatic beta-cells. The autoimmune response against beta-cells appears to begin in the pancreatic lymph node where T cells, which have escaped negative selection in the thymus, first meet beta-cell antigens presented by dendritic cells. Proinsulin is an important antigen in early diabetes. T cells migrate to the islets via the circulation and establish insulitis initially around the islets. T cells within insulitis are specific for islet antigens rather than bystanders. Pathogenic CD4+ T cells may recognize peptides from proinsulin which are produced locally within the islet. CD8+ T cells differentiate into effector T cells in islets and then kill beta-cells, primarily via the perforin-granzyme pathway. Cytokines do not appear to be important cytotoxic molecules in vivo. Maturation of the immune response within the islet is now understood to contribute to diabetes, and highlights the islet as both driver and target of the disease. The majority of our knowledge of these pathogenic processes is derived from the NOD mouse model, although some processes are mirrored in the human disease. However, more work is required to translate the data from the NOD mouse to our understanding of human diabetes pathogenesis. New technology, especially MHC tetramers and modern imaging, will enhance our understanding of the pathogenic mechanisms. PMID:23804258

Graham, Kate L.; Sutherland, Robyn M.; Mannering, Stuart I.; Zhao, Yuxing; Chee, Jonathan; Krishnamurthy, Balasubramanian; Thomas, Helen E.; Lew, Andrew M.; Kay, Thomas W.H.

2012-01-01

425

Global gene expression profiles for life stages of the deadly amphibian pathogen Batrachochytrium dendrobatidis  

PubMed Central

Amphibians around the world are being threatened by an emerging pathogen, the chytrid fungus Batrachochytrium dendrobatidis (Bd). Despite intensive ecological study in the decade since Bd was discovered, little is known about the mechanism by which Bd kills frogs. Here, we compare patterns of global gene expression in controlled laboratory conditions for the two phases of the life cycle of Bd: the free-living zoospore and the substrate-embedded sporangia. We find zoospores to be transcriptionally less complex than sporangia. Several transcripts more abundant in zoospores provide clues about how this motile life stage interacts with its environment. Genes with higher levels of expression in sporangia provide new hypotheses about the molecular pathways involved in metabolic activity, flagellar function, and pathogenicity in Bd. We highlight expression patterns for a group of fungalysin metallopeptidase genes, a gene family thought to be involved in pathogenicity in another group of fungal pathogens that similarly cause cutaneous infection of vertebrates. Finally we discuss the challenges inherent in developing a molecular toolkit for chytrids, a basal fungal lineage separated by vast phylogenetic distance from other well characterized fungi. PMID:18852473

Rosenblum, Erica Bree; Stajich, Jason E.; Maddox, Nicole; Eisen, Michael B.

2008-01-01

426

Deconstructing host-pathogen interactions in Drosophila  

PubMed Central

Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. PMID:21979942

Bier, Ethan; Guichard, Annabel

2012-01-01

427

Susceptibility of pathogenic and nonpathogenic Naegleria ssp  

SciTech Connect

The susceptibility of four species of Naegleria amoebae to complement-mediated lysis was determined. The amoebicidal activity of normal human serum (NHS) and normal guinea pig serum (NGPS) for Naegleria amoebae was measured by an in vitro cytotoxicity assay. Release of radioactivity from amoebae labeled with {sup 3}H-uridine and visual observation with a compound microscope were used as indices of lysis. Susceptibility or resistance to complement-mediated lysis in vitro correlated with the in vivo pathogenic potential. Nonpathogenic Naegleria amoebae were lysed at a faster rate and at higher cell concentrations than were pathogenic amoebae. Electrophoretic analysis of NHS incubated with pathogenic or nonpathogenic Naegleria spp. demonstrated that amoebae activate the complement cascade resulting in the production of C3 and C5 complement cleavage products. Treatment with papain or trypsin for 1 h, but not with sialidase, increase the susceptibility of highly pathogenic, mouse-passaged N. fowleri to lysis. Treatment with actinomycin D, cycloheximide or various protease inhibitors for 4 h did not increase susceptibility to lysis. Neither a repair process involving de novo protein synthesis nor a complement-inactivating protease appear to account for the increase resistance of N. fowleri amoebae to complement-mediated lysis. A binding study with {sup 125}I radiolabeled C9 indicated that the terminal complement component does not remain stably bound to the membrane of pathogenic amoebae.

Whiteman, L.Y.

1988-01-01

428

The toll-dorsal pathway is required for resistance to viral oral infection in Drosophila.  

PubMed

Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Sptzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

Ferreira, Alvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Ins Silva; Martins, Nelson Eduardo; Teixeira, Luis

2014-12-01

429

The Toll-Dorsal Pathway Is Required for Resistance to Viral Oral Infection in Drosophila  

PubMed Central

Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Sptzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

Ferreira, lvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Ins Silva; Martins, Nelson Eduardo; Teixeira, Luis

2014-01-01

430

Pathways to a Diploma  

ERIC Educational Resources Information Center

This article discusses a program at John Adams High School in New York City that helps students who have fallen behind acquire the credits they need to graduate, while still enabling them to hold a job and meet family obligations. The program is one of 20 Young Adult Borough Centers operated by the New York City Department of Education in

Gewertz, Catherine

2007-01-01

431

Pathways of Interdisciplinary Cognition  

ERIC Educational Resources Information Center

In this article, I propose that at the juncture of disciplines, the mind is involved in at least 3 cognitive activities: overcoming internal monologism or monodisciplinarity, attaining provisional integration, and questioning the integration as necessarily partial. This claim is supported by interview data I collected primarily from faculty

Nikitina, Svetlana

2005-01-01

432

Arabidopsis leaf necrosis caused by simulated acid rain is related to the salicylic acid signaling pathway.  

PubMed

Arabidopsis leaves treated with simulated acid rain (SiAR) showed phenotypes similar to necrotic lesions caused by biotic stresses like Pseudomonad infiltration. Exposure of Arabidopsis to SiAR resulted in the up-regulation of genes known to be induced by the salicylic acid (SA)-mediated pathogen resistance response. The expression of enhanced disease susceptibility (EDS), nonexpressor of PR (NPR) and pathogen-related 1 (PR1), all of which are involved in the salicylic acid signaling pathway, were increased after SiAR exposure. However, vegetative storage protein (VSP), a member of the jasmonic acid pathway did not show a significant change in transcript level. SiAR treatment of transgenic plants expressing salicylate hydroxylase (Nah-G), which prevents the accumulation of salicylic acid, underwent more extensive necrosis than wild-type plants, indicating that the signaling pathway activated by SiAR may overlap with the SA-dependent, systemic acquired resistance pathway. Both Col-0 and Nah-G plants showed sensitivity to SiAR and sulfuric SiAR (S-SiAR) by developing necrotic lesions. Neither Col-0 plants nor Nah-G plants showed sensitivity to nitric SiAR (N-SiAR). These results suggest that SiAR activates at least the salicylic acid pathway and activation of this pathway is sensitive to sulfuric acid. PMID:16549362

Lee, Youngmi; Park, Jongbum; Im, Kyunghoan; Kim, Kiyoon; Lee, Jungwoo; Lee, Kyungyeoll; Park, Jung-An; Lee, Taek-Kyun; Park, Dae-Sup; Yang, Joo-Sung; Kim, Donggiun; Lee, Sukchan

2006-01-01

433

Reconceptualizing the chlamydial inclusion as a pathogen-specified parasitic organelle: an expanded role for Inc proteins  

PubMed Central

Chlamydia is an obligate intracellular pathogen that develops in the host cell in a vacuole termed the chlamydial inclusion. The prevailing concept of the chlamydial inclusion is of a parasitophorous vacuole. Here, the inclusion is the recipient of one-way host-pathogen interactions thus draining nutrients from the cell and negatively impacting it. While Chlamydia orchestrates some aspects of cell function, recent data indicate host cells remain healthy up until, and even after, chlamydial egress. Thus, while Chlamydia relies on the host cell for necessary metabolites, the overall function of the host cell, during chlamydial growth and development, is not grossly disturbed. This is consistent with the obligate intracellular organism's interest to maintain viability of its host. To this end, Chlamydia expresses inclusion membrane proteins, Incs, which serve as molecular markers for the inclusion membrane. Incs also contribute to the physical structure of the inclusion membrane and facilitate host-pathogen interactions across it. Given the function of Incs and the dynamic interactions that occur at the inclusion membrane, we propose that the inclusion behaves similarly to an organelle-albeit one that benefits the pathogen. We present the hypothesis that the chlamydial inclusion acts as a pathogen-specified parasitic organelle. This representation integrates the inclusion within existing subcellular trafficking pathways to divert a subset of host-derived metabolites thus maintaining host cell homeostasis. We review the known interactions of the chlamydial inclusion with the host cell and discuss the role of Inc proteins in the context of this model and how this perspective can impact the study of these proteins. Lessons learnt from the chlamydial pathogen-specified parasitic organelle can be applied to other intracellular pathogens. This will increase our understanding of how intracellular pathogens engage the host cell to establish their unique developmental niches. PMID:25401095

Moore, Elizabeth R.; Ouellette, Scot P.

2014-01-01

434

Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 4. Infective doses and pathogen carriage.  

PubMed

In this article, the fourth in a series reviewing the role of food workers in foodborne outbreaks, background information on the presence of enteric pathogens in the community, the numbers of organisms required to initiate an infection, and the length of carriage are presented. Although workers have been implicated in outbreaks, they were not always aware of their infections, either because they were in the prodromic phase before symptoms began or because they were asymptomatic carriers. Pathogens of fecal, nose or throat, and skin origin are most likely to be transmitted by the hands, highlighting the need for effective hand hygiene and other barriers to pathogen contamination, such as no bare hand contact with ready-to-eat food. The pathogens most likely to be transmitted by food workers are norovirus, hepatitis A virus, Salmonella, Shigella, and Staphylococcus aureus. However, other pathogens have been implicated in worker-associated outbreaks or have the potential to be implicated. In this study, the likelihood of pathogen involvement in foodborne outbreaks where infected workers have been implicated was examined, based on infectious dose, carriage rate in the community, duration of illness, and length of pathogen excretion. Infectious dose estimates are based on volunteer studies (mostly early experiments) or data from outbreaks. Although there is considerable uncertainty associated with these data, some pathogens appear to be able to infect at doses as low as 1 to 100 units, including viruses, parasites, and some bacteria. Lengthy postsymptomatic shedding periods and excretion by asymptomatic individuals of many enteric pathogens is an important issue for the hygienic management of food workers. PMID:19044283

Todd, Ewen C D; Greig, Judy D; Bartleson, Charles A; Michaels, Barry S

2008-11-01

435

Evolution of N-species Kimura/voter models towards criticality, a surrogate for general models of accidental pathogens  

NASA Astrophysics Data System (ADS)

In models for accidental pathogens, with the paradigmatic epidemiological system of bacterial meningitis, there was evolution towards states exhibiting critical fluctuations with power law behaviour observed [1]. This is a model with many possibly pathogenic strains essentially evolving independently to low pathogenicity. A first and previous study had shown that in the limit of vanishing pathogenicity there are critical fluctuations with power law distributions observed, already when only two strains interact [2]. This earlier version of a two strain model was very recently reinvestigated [3] and named as Stollenwerk-Jansen model (SJ). Muoz et al. demonstrated that this two-strain model for accidental pathogens is in the universality class of the so-called voter model. Though this model clearly shows criticality, its control parameter, the pathogenicity, is not self-tuning towards criticality. However, the multi-strain version mentioned above [1] is well evolving towards criticality, as well as a spatially explicit version of this, shown in [4] p. 155. These models of multi-strain type including explicitly mutations of the pathogenicity can be called SJ-models of type II [5]. Since the original epidemiological model is of SIRYX-type, the evolution to zero pathogenicity is slow and perturbed by large population noise. In the present article we now show on the basis of the notion of the voter-model universality classes the evolution of n-voter models with mutaion towards criticality, now much less perturbed by population noise, hence demonstrating a clear mechanism of self-organized criticality in the sense of [6, 7]. The present results have wide implications for many diseases in which a large proportion of infections is asymptomatic, meaning that the system has already evolved towards an average low pathogenicity. This holds not only for the original paradigmatic case of bacterial meningitis, but was reecently also suggested for example for dengue fever (DENFREE project).

Ghaffari, Peyman; Stollenwerk, Nico

2012-09-01

436

Detection of Pathogens Using AFM and SPR  

NASA Astrophysics Data System (ADS)

A priori detection of pathogens in food and water has become a subject of paramount importance. Several recent incidents have resulted in the government passing stringent regulations for tolerable amounts of contamination of food products. Identification and/or monitoring of bacterial contamination in food are critical. The conventional methods of pathogen detection require time-consuming steps to arrive disembark at meaningful measurement in a timely manner as the detection time exceeds the time in which perishable food recycles through the food chain distribution. The aim of this presentation is to outline surface plasmon resonance (SPR) and atomic force microscopy (AFM) as two methods for fast detect6ion of pathogens. Theoretical basis of SPR and experimental results of SPR and AFM on E. coli O157:H7 and prion are presented.

Vaseashta, Ashok

2005-03-01

437

Discovery of virulence factors of pathogenic bacteria.  

PubMed

Discovering virulence factors of pathogenic bacteria is a key in understanding pathogenesis and for identification of targets for novel drugs and design of new vaccines. Comparative genomics, transcriptomics, and proteomics have become the popular tools in discovering the virulence factors in bacterial pathogens, such as Neisseria meningitidis, Yersinia pestis, Mycobacterium tuberculosis, and Staphylococcus aureus. In addition, proteomics has been employed successfully in the study of the mechanism of post-translationally modified proteins of bacterial pathogens. Once the putative virulence factors are identified by genomics and/or proteomics, their functions and mechanisms can be further investigated by phenotypic analyses including mutagenesis and biochemical methods and/or structural biology. Combination of these techniques will accelerate the developments of therapeutic drugs and vaccines in combating bacterial diseases. PMID:18284925

Wu, Hsing-Ju; Wang, Andrew H-J; Jennings, Michael P

2008-02-01

438

Mitochondrial DNA analysis: polymorphisms and pathogenicity  

PubMed Central

The investigation of mtDNA disease can be relatively straightforward if a person has a recognisable phenotype and if it is possible