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Sample records for completely protects aspergillus

  1. The complete mitochondrial genome sequence of Aspergillus flavus.

    PubMed

    Yan, Zhengsong; Chen, Dan; Shen, Yiping; Ye, Baodong

    2016-07-01

    Aspergillus flavus is a haploid filamentous fungus that is common in the environment and has been implicated in human infections. The complete mitochondrial genome of A. flavus has been determined by high-throughput sequencing technology in this work. Our study revealed that the mitochondrial genome of A. flavus is 31,602 bp long, with an A + T content of 74.83%, which consists of a usual set of mitochondrial proteins and RNA genes, including large and small ribosomal RNAs, 15 proteins, and 20 tRNA genes and contains two introns. Notably, it also contains two hypothetical proteins without obvious homology to any known proteins. All structural genes are located on one strand and are apparently transcribed in one direction. Codon usage analysis indicated that all protein coding genes employ the standard fungal mitochondrial start and stop codons; and the nucleotide bias toward AT was also reflected in the codon usage. The complete mitochondrial genomes of A. flavus would be useful for future investigation of the genetic, evolution, and clinical identification of Aspergillus species. PMID:25922962

  2. Complete mitochondrial genome of an Amynthas earthworm, Amynthas aspergillus (Oligochaeta: Megascolecidae).

    PubMed

    Zhang, Liangliang; Jiang, Jibao; Dong, Yan; Qiu, Jiangping

    2016-05-01

    We have determined the mitochondrial genome of the first Amynthas earthworm, Amynthas aspergillus (Perrier, 1872), which is a natural medical resource in Chinese traditional medicine. Its mitogenome is 15,115 bp in length containing 37 genes with the same contents and order as other sequenced earthworms. All genes are encoded by the same strand, all 13 PCGs use ATG as start codon. The content of A + T is 63.04% for A. aspergillus (33.41% A, 29.63% T, 14.56% G and 22.41% C). The complete mitochondrial genomes of A. aspergillus would be useful for the reconstruction of Oligochaeta polygenetic relationships. PMID:25329289

  3. Complete Genome Sequence of Soil Fungus Aspergillus terreus (KM017963), a Potent Lovastatin Producer.

    PubMed

    Savitha, Janakiraman; Bhargavi, S D; Praveen, V K

    2016-01-01

    We report the complete genome of Aspergillus terreus (KM017963), a tropical soil isolate. The genome sequence is 29 Mb, with a G+C content of 51.12%. The genome sequence of A. terreus shows the presence of the complete gene cluster responsible for lovastatin (an anti-cholesterol drug) production in a single scaffold (1.16). PMID:27284150

  4. Complete Genome Sequence of Soil Fungus Aspergillus terreus (KM017963), a Potent Lovastatin Producer

    PubMed Central

    Bhargavi, S. D.; Praveen, V. K.

    2016-01-01

    We report the complete genome of Aspergillus terreus (KM017963), a tropical soil isolate. The genome sequence is 29 Mb, with a G+C content of 51.12%. The genome sequence of A. terreus shows the presence of the complete gene cluster responsible for lovastatin (an anti-cholesterol drug) production in a single scaffold (1.16). PMID:27284150

  5. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

    PubMed Central

    Savers, Amélie; Rasid, Orhan; Parlato, Marianna; Brock, Matthias; Jouvion, Gregory; Ryffel, Bernhard; Cavaillon, Jean-Marc; Eberl, Gerard; Ibrahim-Granet, Oumaïma

    2016-01-01

    Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection. PMID:27078879

  6. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge.

    PubMed

    Savers, Amélie; Rasid, Orhan; Parlato, Marianna; Brock, Matthias; Jouvion, Gregory; Ryffel, Bernhard; Cavaillon, Jean-Marc; Eberl, Gerard; Ibrahim-Granet, Oumaïma

    2016-01-01

    Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection. PMID:27078879

  7. Office of River Protection Mission Completion Strategy

    SciTech Connect

    Wiegman, S. A.; Hewitt, W. M.; Yuracko, K.; Holbrook, J. H.

    2002-02-26

    DOE's Office of River Protection (ORP) is readying itself to commence construction of a Waste Treatment Plant (WTP) that will start the process of turning Hanford tank waste into glass. The plant is state-of-the art and includes reasonable flexibility to improve operations as technology and operational understandings improve. During its 40 year design life the plant has the capability to treat half of the total volume of tank waste and reduce risk to the public by up to ninety percent. Looking beyond initial processing towards the project end state, however, it is apparent that ORP's baseline approach is part of the issue raised by the DOE Secretary when he said that $300 billion and 75 years is too costly and too long for DOE's environmental cleanups. ORP has reviewed its cost and schedule drivers and has started identifying areas where better technologies and risk-based strategies could substantially decrease its life cycle cost and schedule. Specific technologies under consideration will be discussed along with expected return on investment. ORP is totally committed to taking all steps necessary during cleanup to protect human health and the environment and to comply with appropriate regulations and commitments. But, ORP is also very conscious of the fact that the history of Hanford production and tank farm operations has resulted in very large tank-to-tank variabilities in the waste constituents. Not all tank wastes demand the same high level of rigor in treatment as provided by the WTP in order to protect people and the environment. Parallel treatment paths, keyed to the hazards and chemical challenges each tank presents, need to be developed. The WTP vitrification capabilities should be deployed for the higher risk wastes that require vitrification. By getting wastes in the proper paths for treatment based upon their chemical characteristics and inherent risks, ORP will be able to both accelerate the cleanup schedule and bring its life cycle and annual

  8. A Non-canonical Melanin Biosynthesis Pathway Protects Aspergillus terreus Conidia from Environmental Stress.

    PubMed

    Geib, Elena; Gressler, Markus; Viediernikova, Iuliia; Hillmann, Falk; Jacobsen, Ilse D; Nietzsche, Sandor; Hertweck, Christian; Brock, Matthias

    2016-05-19

    Melanins are ubiquitous pigments found in all kingdoms of life. Most organisms use them for protection from environmental stress, although some fungi employ melanins as virulence determinants. The human pathogenic fungus Aspergillus fumigatus and related Ascomycetes produce dihydroxynaphthalene- (DHN) melanin in their spores, the conidia, and use it to inhibit phagolysosome acidification. However, biosynthetic origin of melanin in a related fungus, Aspergillus terreus, has remained a mystery because A. terreus lacks genes for synthesis of DHN-melanin. Here we identify genes coding for an unusual NRPS-like enzyme (MelA) and a tyrosinase (TyrP) that A. terreus expressed under conidiation conditions. We demonstrate that MelA produces aspulvinone E, which is activated for polymerization by TyrP. Functional studies reveal that this new pigment, Asp-melanin, confers resistance against UV light and hampers phagocytosis by soil amoeba. Unexpectedly, Asp-melanin does not inhibit acidification of phagolysosomes, thus likely contributing specifically to survival of A. terreus conidia in acidic environments. PMID:27133313

  9. Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection

    PubMed Central

    Karki, Rajendra; Man, Si Ming; Malireddi, R.K. Subbarao; Gurung, Prajwal; Vogel, Peter; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi

    2015-01-01

    SUMMARY Invasive pulmonary aspergillosis is a leading cause of infection-associated mortality in immunocompromised individuals. Aspergillus fumigatus infection produces ligands that could activate inflammasomes but the contribution of these host defenses remains unclear. We show that two inflammasome receptors, AIM2 and NLRP3, recognize intracellular A. fumigatus and collectively induce protective immune responses. Mice lacking both AIM2 and NLRP3 fail to confine Aspergillus hyphae to inflammatory foci, leading to widespread hyphal dissemination to lung blood vessels. These mice succumb to infection more rapidly than WT mice or mice lacking a single inflammasome receptor. AIM2 and NLRP3 activation initiates assembly of a single cytoplasmic inflammasome platform, composed of the adaptor protein ASC along with caspase-1 and caspase-8. Combined actions of caspase-1 and caspase-8 lead to processing of proinflammatory cytokines IL-1β and IL-18 that critically control the infection. Thus, AIM2 and NLRP3 form a dual cytoplasmic surveillance system that orchestrates responses against A. fumigatus infection. PMID:25704009

  10. The complete biodegradation pathway of ellagitannins by Aspergillus niger in solid-state fermentation.

    PubMed

    Ascacio-Valdés, Juan A; Aguilera-Carbó, Antonio F; Buenrostro, José J; Prado-Barragán, Arely; Rodríguez-Herrera, Raúl; Aguilar, Cristóbal N

    2016-04-01

    Our research group has found preliminary evidences of the fungal biodegradation pathway of ellagitannins, revealing first the existence of an enzyme responsible for ellagitannins degradation, which hydrolyzes pomegranate ellagitannins and it was called ellagitannase or elagitannin acyl hydrolase. However, it is necessary to generate new and clear information in order to understand the ellagitannin degradation mechanisms. This work describes the distinctive and unique features of ellagitannin metabolism in fungi. In this study, hydrolysis of pomegranate ellagitannins by Aspergillus niger GH1 was studied by solid-state culture using polyurethane foam as support and pomegranate ellagitannins as substrate. The experiment was performed during 36 h. Results showed that ellagitannin biodegradation started after 6 h of fermentation, reaching the maximal biodegradation value at 18 h. It was observed that ellagitannase activity appeared after 6 h of culture, then, the enzymatic activity was maintained up to 24 h of culture reaching 390.15 U/L, after this period the enzymatic activity decreased. Electrophoretic band for ellagitannase was observed at 18 h. A band obtained using non-denaturing electrophoresis was identified as ellagitannase, then, a tandem analysis to reveal the ellagitannase activity was performed using Petri plate with pomegranate ellagitannins. The extracts were analyzed by HPLC/MS to evaluate ellagitannins degradation. Punicalin, gallagic acid, and ellagic acid were obtained from punicalagin. HPLC/MS analysis identified the gallagic acid as an intermediate molecule and immediate precursor of ellagic acid. The potential application of catabolic metabolism of ellagitannin hydrolysis for ellagic acid production is outlined. PMID:26915983

  11. Vaccinations with recombinant variants of Aspergillus fumigatus allergen Asp f 3 protect mice against invasive aspergillosis.

    PubMed

    Ito, James I; Lyons, Joseph M; Hong, Teresa B; Tamae, Daniel; Liu, Yi-Kuang; Wilczynski, Sharon P; Kalkum, Markus

    2006-09-01

    A vaccine that effectively protects immunocompromised patients against invasive aspergillosis is a novel approach to a universally fatal disease. Here we present a rationale for selection and in vivo testing of potential protein vaccine candidates, based on the modification of an immunodominant fungal allergen for which we demonstrate immunoprotective properties. Pulmonary exposure to viable Aspergillus fumigatus conidia as well as vaccination with crude hyphal extracts protects corticosteroid-immunosuppressed mice against invasive aspergillosis (J. I. Ito and J. M. Lyons, J. Infect. Dis. 186:869-871, 2002). Sera from the latter animals contain antibodies with numerous and diverse antigen specificities, whereas sera from conidium-exposed mice contain antibodies predominantly against allergen Asp f 3 (and some against Asp f 1), as identified by mass spectrometry. Subcutaneous immunization with recombinant Asp f 3 (rAsp f 3) but not with Asp f 1 was protective. The lungs of Asp f 3-vaccinated survivors were free of hyphae and showed only a patchy low-density infiltrate of mononuclear cells. In contrast, the nonimmunized animals died with invasive hyphal elements and a compact peribronchial infiltrate of predominantly polymorphonuclear leukocytes. Three truncated versions of rAsp f 3, spanning amino acid residues 15 to 168 [rAsp f 3(15-168)], 1 to 142, and 15 to 142 and lacking the known bipartite sequence required for IgE binding, were also shown to be protective. Remarkably, vaccination with either rAsp f 3(1-142) or rAsp f 3(15-168) drastically diminished the production of antigen-specific antibodies compared to vaccination with the full-length rAsp f 3(1-168) or the double-truncated rAsp f 3(15-142) version. Our findings point to a possible mechanism in which Asp f 3 vaccination induces a cellular immune response that upon infection results in the activation of lymphocytes that in turn enhances and/or restores the function of corticosteroid-suppressed macrophages

  12. Enhanced DPPH radical scavenging activity and DNA protection effect of litchi pericarp extract by Aspergillus awamori bioconversion

    PubMed Central

    2012-01-01

    Background Litchi (Litchi chinensis Sonn.) pericarp is a major byproduct which contains a significant amount of polyphenol. This study was designed to biotransformation litchi pericarp extract (LPE) by Aspergillus awamori to produce more bioactive compounds with stronger antioxidant activities. Results The study exhibited that the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities significantly (p < 0.05) increased from 15.53% to 18.23% in the water-extracted fraction and from 25.41% to 36.82% in the ethyl acetate-extracted fraction. Application of DNA cleavage assay further demonstrated the enhanced protection effect of the fermented phenolics on DNA damage. It is also noted that the water-extracted fraction of the fermented LPE possessed a much stronger capacity than the ethyl acetate-extracted fraction to prevent from damage of supercoiled DNA. Interestingly, it was found that some new compounds such as catechin and quercetin appeared after of A. awamori fermentation of LPE, which could account for the enhanced antioxidant activity. Conclusion The DPPH radical scavenging activity and DNA protection effect of LPE were increased by Aspergillus awamori bioconversion while some compounds responsible for the enhanced antioxidant activity were identified. This study provided an effective way of utilizing fruit pericarp as a readily accessible source of the natural antioxidants in food industry and, thus, extended the application area such as fruit by-products. PMID:23016522

  13. Potential of essential oils for protection of grains contaminated by aflatoxin produced by Aspergillus flavus

    PubMed Central

    Esper, Renata H.; Gonçalez, Edlayne; Marques, Marcia O. M.; Felicio, Roberto C.; Felicio, Joana D.

    2014-01-01

    Aflatoxin B1 (AFB1) is a highly toxic and carcinogenic metabolite produced by Aspergillus species on food and agricultural commodities. Inhibitory effects of essential oils of Ageratum conyzoides (mentrasto) and Origanum vulgare (oregano) on the mycelial growth and aflatoxin B1 production by Aspergillus flavus have been studied previously in culture medium. The aim of this study was to evaluate aflatoxin B1 production by Aspergillus flavus in real food systems (corn and soybean) treated with Ageratum conyzoides (mentrasto) and Origanum vulgare (oregano) essential oils. Samples with 60 g of the grains were treated with different volumes of essential oils, 200, 100, 50, and 10 μL for oregano and 50, 30, 15, and 10 μL for mentrasto. Fungal growth was evaluated by disk diffusion method. Aflatoxin B1 production was evaluated inoculating suspensions of A. flavus containing 1.3 × 105 spores/mL in 60 g of grains (corn and soybeans) after adjusting the water activity at 0.94. Aflatoxin was quantified by photodensitometry. Fungal growth and aflatoxin production were inhibited by essential oils, but the mentrasto oil was more effective in soybeans than that of oregano. On the other hand, in corn samples, the oregano essential oil was more effective than that of mentrasto. Chemical compositions of the essential oils were also investigated. The GC/MS oils analysis showed that the main component of mentrasto essential oil is precocene I and of the main component of oregano essential oil is 4-terpineol. The results indicate that both essential oils can become an alternative for the control of aflatoxins in corn and soybeans. PMID:24926289

  14. A protective endophyte of maize: Acremonium zeae antibiotics inhibitory to Aspergillus flavus and Fusarium verticillioides.

    PubMed

    Wicklow, Donald T; Roth, Shoshannah; Deyrup, Stephen T; Gloer, James B

    2005-05-01

    The maize endophyte Acremonium zeae is antagonistic to kernel rotting and mycotoxin producing fungi Aspergillus flavus and Fusarium verticillioides in cultural tests for antagonism, and interferes with A. flavus infection and aflatoxin contamination of preharvest maize kernels. Chemical studies of an organic extract from maize kernel fermentations of Acremonium zeae (NRRL 13540), which displayed significant antifungal activity against Aspergillus flavus and F. verticillioides, revealed that the metabolites accounting for this activity were two newly reported antibiotics pyrrocidines A and B. Pyrrocidines were detected in fermentation extracts for 12 NRRL cultures of Acremonium zeae isolated from maize kernels harvested in Illinois (4/4 cultures), North Carolina (5/5), Georgia (1/2) and unrecorded locations within the USA (2/2). Pyrrocidine B was detected by LCMSMS in whole symptomatic maize kernels removed at harvest from ears of a commercial hybrid that were wound-inoculated in the milk stage with A. zeae (NRRL 13540) or (NRRL 13541). The pyrrocidines were first reported from the fermentation broth of an unidentified filamentous fungus LL-Cyan426, isolated from a mixed Douglas Fir hardwood forest on Crane Island Preserve, Washington, in 1993. Pyrrocidine A exhibited potent activity against most Gram-positive bacteria, including drug-resistant strains, and was also active against the yeast Candida albicans. In an evaluation of cultural antagonism between 13 isolates of A. zeae in pairings with A. flavus (NRRL 6541) and F. verticillioides (NRRL 25457), A. zeae (NRRL 6415) and (NRRL 34556) produced the strongest reaction, inhibiting both organisms at a distance while continuing to grow through the resulting clear zone at an unchanged rate. Maximum colony diameters for A. zeae (NRRL 6415) and (NRRL 13540), on potato dextrose agar after 14 d, were attained within the range of 25-30 degrees C, with less growth recorded at 15 degrees and 37.5 degrees and no growth at 5

  15. Heme-Biosynthetic Porphobilinogen Deaminase Protects Aspergillus nidulans from Nitrosative Stress

    PubMed Central

    Zhou, Shengmin; Narukami, Toshiaki; Nameki, Misuzu; Ozawa, Tomoko; Kamimura, Yosuke; Hoshino, Takayuki

    2012-01-01

    Microorganisms have developed mechanisms to combat reactive nitrogen species (RNS); however, only a few of the fungal genes involved have been characterized. Here we screened RNS-resistant Aspergillus nidulans strains from fungal transformants obtained by introducing a genomic DNA library constructed in a multicopy vector. We found that the AN0121.3 gene (hemC) encodes a protein similar to the heme biosynthesis enzyme porphobilinogen deaminase (PBG-D) and facilitates RNS-tolerant fungal growth. The overproduction of PBG-D in A. nidulans promoted RNS tolerance, whereas PBG-D repression caused growth that was hypersensitive to RNS. PBG-D levels were comparable to those of cellular protoheme synthesis as well as flavohemoglobin (FHb; encoded by fhbA and fhbB) and nitrite reductase (NiR; encoded by niiA) activities. Both FHb and NiR are hemoproteins that consume nitric oxide and nitrite, respectively, and we found that they are required for maximal growth in the presence of RNS. The transcription of hemC was upregulated by RNS. These results demonstrated that PBG-D is a novel NO-tolerant protein that modulates the reduction of environmental NO and nitrite levels by FHb and NiR. PMID:22038601

  16. Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation.

    PubMed

    Hillmann, Falk; Novohradská, Silvia; Mattern, Derek J; Forberger, Tilmann; Heinekamp, Thorsten; Westermann, Martin; Winckler, Thomas; Brakhage, Axel A

    2015-08-01

    Filamentous fungi represent classical examples for environmentally acquired human pathogens whose major virulence mechanisms are likely to have emerged long before the appearance of innate immune systems. In natural habitats, amoeba predation could impose a major selection pressure towards the acquisition of virulence attributes. To test this hypothesis, we exploited the amoeba Dictyostelium discoideum to study its interaction with Aspergillus fumigatus, two abundant soil inhabitants for which we found co-occurrence in various sites. Fungal conidia were efficiently taken up by D. discoideum, but ingestion was higher when conidia were devoid of the green fungal spore pigment dihydroxynaphtalene melanin, in line with earlier results obtained for immune cells. Conidia were able to survive phagocytic processing, and intracellular germination was initiated only after several hours of co-incubation which eventually led to a lethal disruption of the host cell. Besides phagocytic interactions, both amoeba and fungus secreted cross inhibitory factors which suppressed fungal growth or induced amoeba aggregation with subsequent cell lysis, respectively. On the fungal side, we identified gliotoxin as the major fungal factor killing Dictyostelium, supporting the idea that major virulence attributes, such as escape from phagocytosis and the secretion of mycotoxins are beneficial to escape from environmental predators. PMID:25684622

  17. Aspergillus: introduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Species in the genus Aspergillus possess versatile metabolic activities that impact our daily life both positively and negatively. Aspergillus flavus and Aspergillus oryzae are closely related fungi. While the former is able to produce carcinogenic aflatoxins and is an etiological agent of aspergill...

  18. The Aspergillus fumigatus Protein GliK Protects against Oxidative Stress and Is Essential for Gliotoxin Biosynthesis

    PubMed Central

    Gallagher, Lorna; Owens, Rebecca A.; Dolan, Stephen K.; O'Keeffe, Grainne; Schrettl, Markus; Kavanagh, Kevin; Jones, Gary W.

    2012-01-01

    The function of a number of genes in the gliotoxin biosynthetic cluster (gli) in Aspergillus fumigatus remains unknown. Here, we demonstrate that gliK deletion from two strains of A. fumigatus completely abolished gliotoxin biosynthesis. Furthermore, exogenous H2O2 (1 mM), but not gliotoxin, significantly induced A. fumigatus gliK expression (P = 0.0101). While both mutants exhibited significant sensitivity to both exogenous gliotoxin (P < 0.001) and H2O2 (P < 0.01), unexpectedly, exogenous gliotoxin relieved H2O2-induced growth inhibition in a dose-dependent manner (0 to 10 μg/ml). Gliotoxin-containing organic extracts derived from A. fumigatus ATCC 26933 significantly inhibited (P < 0.05) the growth of the ΔgliK26933 deletion mutant. The A. fumigatus ΔgliK26933 mutant secreted metabolites, devoid of disulfide linkages or free thiols, that were detectable by reverse-phase high-performance liquid chromatography and liquid chromatography-mass spectrometry with m/z 394 to 396. These metabolites (m/z 394 to 396) were present at significantly higher levels in the culture supernatants of the A. fumigatus ΔgliK26933 mutant than in those of the wild type (P = 0.0024 [fold difference, 24] and P = 0.0003 [fold difference, 9.6], respectively) and were absent from A. fumigatus ΔgliG. Significantly elevated levels of ergothioneine were present in aqueous mycelial extracts of the A. fumigatus ΔgliK26933 mutant compared to the wild type (P < 0.001). Determination of the gliotoxin uptake rate revealed a significant difference (P = 0.0045) between that of A. fumigatus ATCC 46645 (9.3 pg/mg mycelium/min) and the ΔgliK46645 mutant (31.4 pg/mg mycelium/min), strongly suggesting that gliK absence and the presence of elevated ergothioneine levels impede exogenously added gliotoxin efflux. Our results confirm a role for gliK in gliotoxin biosynthesis and reveal new insights into gliotoxin functionality in A. fumigatus. PMID:22903976

  19. Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke

    PubMed Central

    Chen-Bee, Cynthia H.; Frostig, Ron D.

    2010-01-01

    Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential. PMID:20585659

  20. Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.

    PubMed

    Oscherwitz, Jon; Yu, Fen; Jacobs, Jana L; Cease, Kemp B

    2013-03-01

    We previously showed that a multiple antigenic peptide (MAP) vaccine displaying amino acids (aa) 304 to 319 from the 2β2-2β3 loop of protective antigen was capable of protecting rabbits from an aerosolized spore challenge with Bacillus anthracis Ames strain. Antibodies to this sequence, referred to as the loop-neutralizing determinant (LND), are highly potent at neutralizing lethal toxin yet are virtually absent in rabbit and human protective antigen (PA) antiserum. While the MAP vaccine was protective against anthrax, it contains a single heterologous helper T cell epitope which may be suboptimal for stimulating an outbred human population. We therefore engineered a recombinant vaccine (Rec-LND) containing two tandemly repeated copies of the LND fused to maltose binding protein, with enhanced immunogenicity resulting from the p38/P4 helper T cell epitope from Schistosoma mansoni. Rec-LND was found to be highly immunogenic in four major histocompatibility complex (MHC)-diverse strains of mice. All (7/7) rabbits immunized with Rec-LND developed high-titer antibody, 6 out of 7 developed neutralizing antibody, and all rabbits were protected from an aerosolized spore challenge of 193 50% lethal doses (LD(50)) of the B. anthracis Ames strain. Survivor serum from Rec-LND-immunized rabbits revealed significantly increased neutralization titers and specific activity compared to prechallenge levels yet lacked PA or lethal factor (LF) antigenemia. Control rabbits immunized with PA, which were also completely protected, appeared sterilely immune, exhibiting significant declines in neutralization titer and specific activity compared to prechallenge levels. We conclude that Rec-LND may represent a prototype anthrax vaccine for use alone or potentially combined with PA-containing vaccines. PMID:23283638

  1. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens.

    PubMed

    Madan, T; Kishore, U; Singh, M; Strong, P; Clark, H; Hussain, E M; Reid, K B; Sarma, P U

    2001-02-01

    Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (AFU:). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by AFU: antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of AFU:-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A-treated ABPA mice, and up to 16 days in the SP-D- or rSP-D-treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-gamma was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions. PMID:11181646

  2. 76 FR 16297 - Aspergillus flavus

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ...This regulation establishes an exemption from the requirement of a tolerance for residues of the microbial pesticide, Aspergillus flavus AF36, in or on corn food and feed commodities, when applied/used as an antifungal agent. The Arizona Cotton Research and Protection Council submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an amendment to the......

  3. Complete protection of mice from respiratory syncytial virus infection following mucosal delivery of synthetic peptide vaccines.

    PubMed

    Bastien, N; Trudel, M; Simard, C

    1999-02-26

    We have previously shown that intraperitoneal immunization of BALB/c mice with the 14 amino-acid long synthetic peptides G/174-187 and BG/174-187, representing the region 174-187 of the G-glycoprotein from human (H) and bovine (B) respiratory syncytial virus (RSV), respectively, completely protects animals from infection with the corresponding virus. A current goal in vaccine development being the delivery of noninvasive protective antigens via mucosal surfaces, we have evaluated the immunogenicity and protective efficacy of the two peptides when administered to mice by the intranasal (i.n.) route in the presence or absence of the cholera toxin (CT) as a mucosal adjuvant. The two peptides given alone induced the production of RSV-specific circulating IgG, as revealed by ELISA titers of immune sera. When the peptides were administered intranasally with CT, the higher IgG antibody titer which was induced was within the same order of magnitude as that obtained following i.n. immunization with live RSV or intraperitoneal injection with the peptides, thus demonstrating the stimulatory effect of the CT adjuvant. Moreover, although the peptides fail to induce a detectable level of secretory IgA, all animals immunized i.n. with peptide BG/174-187 (plus or minus CT) and all those immunized with peptide G/174-187 mixed with CT were completely resistant to infection by the corresponding virus. To our knowledge, this is the first study reporting that complete protection against a natural pathogen can be elicited by mucosally delivered synthetic peptides. This supports the usefulness of synthetic peptides in prophylactic vaccination. PMID:10067688

  4. Antibodies Are Required for Complete Vaccine-Induced Protection against Herpes Simplex Virus 2.

    PubMed

    Halford, William P; Geltz, Joshua; Messer, Ronald J; Hasenkrug, Kim J

    2015-01-01

    Herpes simplex virus 2 (HSV-2) 0ΔNLS is a live HSV-2 ICP0- mutant vaccine strain that is profoundly attenuated in vivo due to its interferon-hypersensitivity. Recipients of the HSV-2 0ΔNLS vaccine are resistant to high-dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study, we investigated the requirements for HSV-2 0ΔNLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0ΔNLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV-2 challenge. Diminished antibody responses in recipients of the UV-killed HSV-2 vaccine suggested that antibodies might be playing a critical role in early protection. This hypothesis was investigated in B-cell-deficient μMT mice. Vaccination with live HSV-2 0ΔNLS induced equivalent CD8+ T cell responses in wild-type and μMT mice. Vaccinated μMT mice shed ~40-fold more infectious HSV-2 at 24 hours post-challenge relative to vaccinated wild-type (B-cell+) mice, and most vaccinated μMT mice eventually succumbed to a slowly progressing HSV-2 challenge. Importantly, passive transfer of HSV-2 antiserum restored full protection to HSV-2 0ΔNLS-vaccinated μMT mice. The results demonstrate that B cells are required for complete vaccine-induced protection against HSV-2, and indicate that virus-specific antibodies are the dominant mediators of early vaccine-induced protection against HSV-2. PMID:26670699

  5. Antibodies Are Required for Complete Vaccine-Induced Protection against Herpes Simplex Virus 2

    PubMed Central

    Halford, William P.; Geltz, Joshua; Messer, Ronald J.; Hasenkrug, Kim J.

    2015-01-01

    Herpes simplex virus 2 (HSV-2) 0ΔNLS is a live HSV-2 ICP0- mutant vaccine strain that is profoundly attenuated in vivo due to its interferon-hypersensitivity. Recipients of the HSV-2 0ΔNLS vaccine are resistant to high-dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study, we investigated the requirements for HSV-2 0ΔNLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0ΔNLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV-2 challenge. Diminished antibody responses in recipients of the UV-killed HSV-2 vaccine suggested that antibodies might be playing a critical role in early protection. This hypothesis was investigated in B-cell-deficient μMT mice. Vaccination with live HSV-2 0ΔNLS induced equivalent CD8+ T cell responses in wild-type and μMT mice. Vaccinated μMT mice shed ~40-fold more infectious HSV-2 at 24 hours post-challenge relative to vaccinated wild-type (B-cell+) mice, and most vaccinated μMT mice eventually succumbed to a slowly progressing HSV-2 challenge. Importantly, passive transfer of HSV-2 antiserum restored full protection to HSV-2 0ΔNLS-vaccinated μMT mice. The results demonstrate that B cells are required for complete vaccine-induced protection against HSV-2, and indicate that virus-specific antibodies are the dominant mediators of early vaccine-induced protection against HSV-2. PMID:26670699

  6. Well completion technology. Multiuse polymer protects injection well during drilling, underreaming, gravel packing

    SciTech Connect

    Davis, K.E.; Jarrell, M.D.

    1983-12-12

    Fluids for drilling, gravel-packing, and completion were optimized for an expensive injection well. Successful engineering gave maximum injection rates and no skin damage, while accomplishing all the fundamental drilling and suspension functions of fluids. Formation protection was critical. The approximately $5-million well was planned for chemical waste disposal, and plant capacity is limited by injectivity. This work describes the fluid, hardware, and techniques used. The 3 distinct fluids were variations on the same polymer-based system. Results of tests showed that Kelzan XCD Polymer, a dispersible form of xanthan gum, had the most applicable overall properties.

  7. Oral immunization of mice with recombinant rabies vaccine strain (ERAG3G) induces complete protection

    PubMed Central

    2015-01-01

    Purpose New rabies vaccine bait for both pets and raccoon dogs residing in Korea is needed to eradicate rabies infection among animals. In this study, we constructed a recombinant rabies virus (RABV), the ERAG3G strain, using a reverse genetics system. Then we investigated the efficacy of this strain in mice after oral administration and the safety of this strain in cats after intramuscular administration. Materials and Methods The ERAG3G strain was rescued in BHK/T7-9 cells using the full-length genome mutated at the amino acid position 333 of the glycoprotein gene of RABV and helper plasmids. Four-week-old mice underwent one or two oral administrations of the ERAG3G strain and were challenged with the highly virulent RABV strain CVSN2c 14 days after the second administration. Clinical symptoms were observed and body weights were measured every day after the challenge. Results All mice showed complete protection against virulent RABV. In addition, cats intramuscularly inoculated with the ERAG3G strain showed high antibody titers ranging from 2.62 to 23.9 IU/mL at 28-day postinoculation. Conclusion The oral immunization of the ERAG3G strain plays an important role in conferring complete protection in mice, and intramuscular inoculation of the ERAG3G strain induces the formation of anti-rabies neutralizing antibody in cats. PMID:25648184

  8. Hydrophilins in the filamentous fungus Neosartorya fischeri (Aspergillus fischeri) have protective activity against several types of microbial water stress.

    PubMed

    van Leeuwen, M R; Wyatt, T T; van Doorn, T M; Lugones, L G; Wösten, H A B; Dijksterhuis, J

    2016-02-01

    Hydrophilins are proteins that occur in all domains of life and protect cells and organisms against drought and other stresses. They include most of the late embryogenesis abundant (LEA) proteins and the heat shock protein (HSP) Hsp12. Here, the role of a predicted LEA-like protein (LeamA) and two Hsp12 proteins (Hsp12A and Hsp12B) of Neosartorya fischeri was studied. This filamentous fungus forms ascospores that belong to the most stress-resistant eukaryotic cells described to date. Heterologous expression of LeamA, Hsp12A and Hsp12B resulted in increased tolerance against salt and osmotic stress in Escherichia coli. These proteins were also shown to protect lactate dehydrogenase against dry heat and freeze-thaw cycles in vitro. Deletion of leamA caused diminished viability of sexual ascospores after drought and heat. This is the first report on functionality of Hsp12 and putative LeamA proteins derived from filamentous fungi, and their possible role in N. fischeri ascospore resistance against desiccation, high temperature and osmotic stress is discussed. PMID:26487515

  9. Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

    PubMed Central

    Peterson, Johnny W.; Comer, Jason E.; Noffsinger, David M.; Wenglikowski, Autumn; Walberg, Kristin G.; Chatuev, Bagram M.; Chopra, Ashok K.; Stanberry, Lawrence R.; Kang, Angray S.; Scholz, Wolfgang W.; Sircar, Jagadish

    2006-01-01

    Prevention of inhalation anthrax requires early and extended antibiotic therapy, and therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, and rabbits against anthrax. Control animals challenged with Bacillus anthracis Ames spores by the intranasal route died within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in the murine model, but its efficacy was notably better in guinea pigs. When Swiss-Webster mice, challenged with five 50% lethal doses (LD50s) of anthrax spores, were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and administered to guinea pigs for 6 days, synergistic protection against anthrax was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20 mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge with 100 LD50s of B. anthracis Ames spores, and 100% of the rabbits survived rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6, and 12 h after challenge with anthrax spores resulted in 100% survival; however, delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%, respectively. Serological analysis of sera from various surviving animals 30 days postprimary infection showed development of a species-specific PA enzyme-linked immunosorbent assay antibody titer that correlated with protection against reinfection. Taken together, the effectiveness of human anti-PA antibody alone or in combination with low ciprofloxacin levels may provide the basis for an improved strategy for

  10. Percutaneous extraction of inadvertently placed left-sided pacemaker leads with complete cerebral embolic protection.

    PubMed

    Bahadorani, John N; Schricker, Amir A; Pretorius, Victor G; Birgersdotter-Green, Ulrika; Dominguez, Arturo; Mahmud, Ehtisham

    2015-10-01

    Lead wire malposition is a known, but rare complication of permanent pacemaker or defibrillator implantation. The actual incidence and prevalence is unknown and management options for inadvertent left ventricular lead malposition have not been uniform. Current recommendations include systemic anticoagulation with warfarin or surgical lead removal with circulatory arrest for compelling clinical scenarios. Percutaneous left-sided lead extraction is contraindicated due to the potentially increased risk of thromboembolic complications associated with this procedure. To our knowledge, this is the first report of percutaneous extraction of inadvertently placed left ventricular and left atrial endocardial pacemaker leads with flow-preserving complete cerebral embolic protection. We also review the current literature regarding the incidence, management, and percutaneous extraction of left-sided cardiac leads. PMID:25581608

  11. Aspergillus fumigatus in Poultry

    PubMed Central

    Arné, Pascal; Thierry, Simon; Wang, Dongying; Deville, Manjula; Le Loc'h, Guillaume; Desoutter, Anaïs; Féménia, Françoise; Nieguitsila, Adélaïde; Huang, Weiyi; Chermette, René; Guillot, Jacques

    2011-01-01

    Aspergillus fumigatus remains a major respiratory pathogen in birds. In poultry, infection by A. fumigatus may induce significant economic losses particularly in turkey production. A. fumigatus develops and sporulates easily in poor quality bedding or contaminated feedstuffs in indoor farm environments. Inadequate ventilation and dusty conditions increase the risk of bird exposure to aerosolized spores. Acute cases are seen in young animals following inhalation of spores, causing high morbidity and mortality. The chronic form affects older birds and looks more sporadic. The respiratory tract is the primary site of A. fumigatus development leading to severe respiratory distress and associated granulomatous airsacculitis and pneumonia. Treatments for infected poultry are nonexistent; therefore, prevention is the only way to protect poultry. Development of avian models of aspergillosis may improve our understanding of its pathogenesis, which remains poorly understood. PMID:21826144

  12. Aspergillus antigen skin test (image)

    MedlinePlus

    The aspergillus antigen skin test determines whether or not a person has been exposed to the mold aspergillus. It is performed by injecting an aspergillus antigen under the skin with a needle. After 48 ...

  13. Aspergillus spinal epidural abscess

    SciTech Connect

    Byrd, B.F. III; Weiner, M.H.; McGee, Z.A.

    1982-12-17

    A spinal epidural abscess developed in a renal transplant recipient; results of a serum radioimmunoassay for Aspergillus antigen were positive. Laminectomy disclosed an abscess of the L4-5 interspace and L-5 vertebral body that contained hyphal forms and from which Aspergillus species was cultured. Serum Aspergillus antigen radioimmunoassay may be a valuable, specific early diagnostic test when systemic aspergillosis is a consideration in an immunosuppressed host.

  14. Developmental regulators in Aspergillus fumigatus.

    PubMed

    Park, Hee-Soo; Yu, Jae-Hyuk

    2016-03-01

    The filamentous fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. This fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. The initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousands of genes associated with formation of the asexual developmental structure conidiophore, and biogenesis of conidia. In this review, we summarize key regulators that directly or indirectly govern conidiation in this important pathogenic fungus. Better understanding these developmental regulators may provide insights into the improvement in controlling both beneficial and detrimental aspects of various Aspergillus species. PMID:26920882

  15. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

    PubMed Central

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E.

    2015-01-01

    Background No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. Methodology/Principal Findings The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. Significance VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection

  16. Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges

    PubMed Central

    Smith, James M.; Rastogi, Rachna; Teller, Ryan S.; Srinivasan, Priya; Mesquita, Pedro M. M.; Nagaraja, Umadevi; McNicholl, Janet M.; Hendry, R. Michael; Dinh, Chuong T.; Martin, Amy; Herold, Betsy C.; Kiser, Patrick F.

    2013-01-01

    Topical preexposure prophylaxis interrupts HIV transmission at the site of mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse transcriptase inhibitor tenofovir protected pigtailed macaques depending on the timing of viral challenge relative to gel application. However, modest or no protection was observed in clinical trials. Intravaginal rings (IVRs) may improve efficacy by providing long-term sustained drug delivery leading to constant mucosal antiretroviral concentrations and enhancing adherence. Although a few IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque vaginal challenge model has not been achieved. Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 105 ng/mL (range 1.1 × 104 to 6.6 × 105 ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans. PMID:24043812

  17. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.

    PubMed

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  18. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

    PubMed Central

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  19. Hybridization between Aspergillus flavus and Aspergillus parasiticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To date the sexual stages or teleomorphs have been described for three aflatoxigenic species in Aspergillus section Flavi: Petromyces flavus, P. parasiticus and P. nomius. In this study we examined the possibility of interspecific matings between A. flavus and A. parasiticus. These species can b...

  20. Genomic mining for Aspergillus natural products.

    PubMed

    Bok, Jin Woo; Hoffmeister, Dirk; Maggio-Hall, Lori A; Murillo, Renato; Glasner, Jeremy D; Keller, Nancy P

    2006-01-01

    The genus Aspergillus is renowned for its ability to produce a myriad of bioactive secondary metabolites. Although the propensity of biosynthetic genes to form contiguous clusters greatly facilitates assignment of putative secondary metabolite genes in the completed Aspergillus genomes, such analysis cannot predict gene expression and, ultimately, product formation. To circumvent this deficiency, we have examined Aspergillus nidulans microarrays for expressed secondary metabolite gene clusters by using the transcriptional regulator LaeA. Deletion or overexpression of laeA clearly identified numerous secondary metabolite clusters. A gene deletion in one of the clusters eliminated the production of the antitumor compound terrequinone A, a metabolite not described, from A. nidulans. In this paper, we highlight that LaeA-based genome mining helps decipher the secondary metabolome of Aspergilli and provides an unparalleled view to assess secondary metabolism gene regulation. PMID:16426969

  1. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model.

    PubMed

    Kirkpatrick, Beth D; Whitehead, Stephen S; Pierce, Kristen K; Tibery, Cecilia M; Grier, Palmtama L; Hynes, Noreen A; Larsson, Catherine J; Sabundayo, Beulah P; Talaat, Kawsar R; Janiak, Anna; Carmolli, Marya P; Luke, Catherine J; Diehl, Sean A; Durbin, Anna P

    2016-03-16

    A dengue human challenge model can be an important tool to identify candidate dengue vaccines that should be further evaluated in large efficacy trials in endemic areas. Dengue is responsible for about 390 million infections annually. Protective efficacy results for the most advanced dengue vaccine candidate (CYD) were disappointing despite its ability to induce neutralizing antibodies against all four dengue virus (DENV) serotypes. TV003 is a live attenuated tetravalent DENV vaccine currently in phase 2 evaluation. To better assess the protective efficacy of TV003, a randomized double-blind, placebo-controlled trial in which recipients of TV003 or placebo were challenged 6 months later with a DENV-2 strain, rDEN2Δ30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2Δ30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2Δ30 were protected from infection with rDEN2Δ30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2Δ30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2Δ30 administered 6 months after vaccination. TV003 will be further evaluated in dengue-endemic areas. The controlled dengue human challenge model can accelerate vaccine development by evaluating the protection afforded by the vaccine, thereby eliminating poor candidates from further consideration before the initiation of large efficacy trials. PMID:27089205

  2. Vaccine To Confer to Nonhuman Primates Complete Protection against Multistrain Ebola and Marburg Virus Infections▿

    PubMed Central

    Swenson, Dana L.; Wang, Danher; Luo, Min; Warfield, Kelly L.; Woraratanadharm, Jan; Holman, David H.; Dong, John Y.; Pratt, William D.

    2008-01-01

    Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack. PMID:18216185

  3. New species of Aspergillus producing sterigmatocystin.

    PubMed Central

    Rabie, C J; Steyn, M; van Schalkwyk, G C

    1977-01-01

    A number of species belonging to the genus Aspergillus were evaluated for their toxicity to ducklings and the ability to produce sterigmatocystin. Three new species capable of producing sterigmatocystin were found, namely, Aspergillus aurantio-brunneus, Aspergillus quadrilineatus, and Aspergillus ustus. All three were toxic to ducklings. The production of sterigmatocystin by Aspergillus rugulosus was confirmed, and the toxicity of Aspergillus stellatus and Aspergillus multicolor is described. PMID:406838

  4. Development in Aspergillus

    PubMed Central

    Krijgsheld, P.; Bleichrodt, R.; van Veluw, G.J.; Wang, F.; Müller, W.H.; Dijksterhuis, J.; Wösten, H.A.B.

    2013-01-01

    The genus Aspergillus represents a diverse group of fungi that are among the most abundant fungi in the world. Germination of a spore can lead to a vegetative mycelium that colonizes a substrate. The hyphae within the mycelium are highly heterogeneous with respect to gene expression, growth, and secretion. Aspergilli can reproduce both asexually and sexually. To this end, conidiophores and ascocarps are produced that form conidia and ascospores, respectively. This review describes the molecular mechanisms underlying growth and development of Aspergillus. PMID:23450714

  5. A single immunization with recombinant rabies virus (ERAG3G) confers complete protection against rabies in mice

    PubMed Central

    2014-01-01

    Purpose New alternative bait rabies vaccines applicable to pet dogs and wild animals are needed to eradicate rabies in Korea. In this study, recombinant rabies virus, ERAG3G strain was constructed using reverse genetic system and the safety, efficacy and immunogenicity of the ERAG3G strain was evaluated in mice and dogs. Materials and Methods Using the full-length genome mutated amino acid at position 333 of glycoprotein of rabies virus (RABV) and helper plasmids, the ERAG3G strain was rescued in BHK/T7-9 cells successfully. Mice were inoculated with the ERAG3G strain for safety and efficacy. Safety and immunogenicity of the dog inoculated with the ERAG3G strain (1 mL, 108.0 FAID50/mL) via intramuscular route was evaluated for 28 days after inoculation. Results The ERAG3G strain rescued by reverse genetic system was propagated well in the mouse neuroblastoma cells revealing titer of 108.5 FAID50/mL and was not pathogenic to 4- or 6-week-old mice that received by intramuscular or intracranical route. Immunization with the ERAG3G strain conferred complete protection from lethal RABV in mice. Dogs inoculated with the vaccine candidate via intramuscular route showed high neutralizing antibody titer ranging from 2.62 to 23.9 IU/mL at 28 days postinoculation. Conclusion Our findings suggest that the ERAG3G strain plays an important role in inducing protective efficacy in mice and causes to arise anti-rabies neutralizing antibody in dogs. PMID:25003091

  6. Aspergillus osteoarthritis in acute lymphoblastic leukemia.

    PubMed

    Gunsilius, E; Lass-Flörl, C; Mur, E; Gabl, C; Gastl, G; Petzer, A L

    1999-11-01

    We report an unusual case of arthritis of the right wrist due to Aspergillus fumigatus without evidence for a generalized infection, following chemotherapy for acute lymphoblastic leukemia. The diagnosis was made by surgical biopsy. Amphotericin-B (Am-B) was not tolerated by the patient. Liposomal preparations of Am-B penetrate poorly into bone and cartilage. Therefore, oral itraconazole was given; the arthritis improved and chemotherapy was continued without infectious complications. Two weeks after complete hematopoietic recovery, an intracranial hemorrhage from a mycotic aneurysm of a brain vessel occurred, although the patient was still receiving itraconazole. We emphasize the importance of prompt and thorough efforts to identify the causative agent in immunocompromised patients with a joint infection. Itraconazole is effective in Aspergillus osteoarthritis but, due to its poor penetration into the brain, the combination with a liposomal formulation of Am-B is recommended. PMID:10602898

  7. Cyanocobalamin [c-lactam] inhibits vitamin B12 and causes cytotoxicity in HL60 cells: methionine protects cells completely.

    PubMed

    Matthews, J H

    1997-06-15

    The [c-lactam] derivative of cobalamin antagonizes vitamin B12 in vivo. Therefore, we investigated its effects in tissue culture to develop a model in which to study vitamin B12-deficient hemopoiesis. HL60 cells were cultured in medium containing either methionine or L-homocysteine thiolactone, and various concentrations of 5-methyltetrahydrofolate or pteroylglutamic acid. In medium with L-homocysteine thiolactone, 5-methyltetrahydrofolate, and dialyzed serum, cyanocobalamin [c-lactam] caused cell death, reversible by additional vitamin B12. Pteroylglutamic acid did not prevent this cytotoxic effect. Methionine completely protected cells against cyanocobalamin [c-lactam] for periods of up to 4 months of culture, irrespective of the folate source. Cyanocobalamin [c-lactam] reversibly impaired the incorporation of 5-[14CH3]-tetrahydrofolate and [1-(14)C] propionic acid by intact cells, consistent with inhibition of methionine synthase and methylmalonyl-CoA mutase. A substantial proportion of 5-[14CH3]-tetrahydrofolate uptake could not be suppressed by methionine and may, therefore, have occurred outside of the methionine synthase pathway. These findings are the first indication that cyanocobalamin [c-lactam] antagonizes vitamin B12 in vitro and causes cell death from methionine deficiency. The model should be valuable for investigating the biochemical pathology of vitamin B12-deficient hemopoiesis. The results suggest that methylfolate is not trapped when methionine synthase is inhibited in HL60 cells, but they do not disprove the methylfolate trap hypothesis as applied to normal blood cells. PMID:9192785

  8. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

    PubMed Central

    Barrionuevo, Francisco J; Hurtado, Alicia; Kim, Gwang-Jin; Real, Francisca M; Bakkali, Mohammed; Kopp, Janel L; Sander, Maike; Scherer, Gerd; Burgos, Miguel; Jiménez, Rafael

    2016-01-01

    The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8-/- mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance. DOI: http://dx.doi.org/10.7554/eLife.15635.001 PMID:27328324

  9. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration.

    PubMed

    Barrionuevo, Francisco J; Hurtado, Alicia; Kim, Gwang-Jin; Real, Francisca M; Bakkali, Mohammed; Kopp, Janel L; Sander, Maike; Scherer, Gerd; Burgos, Miguel; Jiménez, Rafael

    2016-01-01

    The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8(-/-) mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance. PMID:27328324

  10. Pituitary aspergillus infection.

    PubMed

    Moore, Lauren A; Erstine, Emily M; Prayson, Richard A

    2016-07-01

    Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed. PMID:26896907

  11. Metabolomics of Aspergillus fumigatus.

    PubMed

    Frisvad, Jens C; Rank, Christian; Nielsen, Kristian F; Larsen, Thomas O

    2009-01-01

    Aspergillus fumigatus is the most important species in Aspergillus causing infective lung diseases. This species has been reported to produce a large number of extrolites, including secondary metabolites, acids, and proteins such as hydrophobins and extracellular enzymes. At least 226 potentially bioactive secondary metabolites have been reported from A. fumigatus that can be ordered into 24 biosynthetic families. Of these families we have detected representatives from the following families of secondary metabolites: fumigatins, fumigaclavines, fumiquinazolines, trypacidin and monomethylsulochrin, fumagillins, gliotoxins, pseurotins, chloroanthraquinones, fumitremorgins, verruculogen, helvolic acids, and pyripyropenes by HPLC with diode array detection and mass spectrometric detection. There is still doubt whether A. fumigatus can produce tryptoquivalins, but all isolates produce the related fumiquinazolines. We also tentatively detected sphingofungins in A. fumigatus Af293 and in an isolate of A. lentulus. The sphingofungins may have a similar role as the toxic fumonisins, found in A. niger. A further number of mycotoxins, including ochratoxin A, and other secondary metabolites have been reported from A. fumigatus, but in those cases either the fungus or its metabolite appear to be misidentified. PMID:18763205

  12. Aspergillus Osteomyelitis: Epidemiology, Clinical Manifestations, Management, and Outcome

    PubMed Central

    Gamaletsou, Maria N.; Rammaert, Blandine; Bueno, Marimelle A.; Moriyama, Brad; Sipsas, Nikolaos V.; Kontoyiannis, Dimitrios P.; Roilides, Emmanuel; Zeller, Valerie; Prinapori, Roberta; Tajaldeen, Saad Jaber; Brause, Barry; Lortholary, Olivier; Walsh, Thomas J.

    2014-01-01

    common sites are vertebrae, ribs, and cranium. Based upon this comprehensive review, management of Aspergillus osteomyelitis optimally includes antifungal therapy and selective surgery to avoid relapse and to achieve a complete response. PMID:24378282

  13. Previously unknown species of Aspergillus.

    PubMed

    Gautier, M; Normand, A-C; Ranque, S

    2016-08-01

    The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. PMID:27263029

  14. Tremorgenic Mycotoxins from Aspergillus Caespitosus

    PubMed Central

    Schroeder, H. W.; Cole, R. J.; Hein, H.; Kirksey, J. W.

    1975-01-01

    Two tremorgenic mycotoxins were isolated from Aspergillus caespitosus, and identified as verruculogen and fumitremorgin B. They were produced at the rate of 172 and 325 mg per kg, respectively, on autoclaved cracked field corn. PMID:1155935

  15. Tremorgenic mycotoxins from Aspergillus caespitosus.

    PubMed

    Schroeder, H W; Cole, R J; Hein, H; Kirksey, J W

    1975-06-01

    Two tremorgenic mycotoxins were isolated from Aspergillus caespitosus, and identified as verruculogen and fumitremorgin B. They were produced at the rate of 172 and 325 mg per kg, respectively, on autoclaved cracked field corn. PMID:1155935

  16. Cryptic Aspergillus nidulans Antimicrobials▿

    PubMed Central

    Giles, Steve S.; Soukup, Alexandra A.; Lauer, Carrie; Shaaban, Mona; Lin, Alexander; Oakley, Berl R.; Wang, Clay C. C.; Keller, Nancy P.

    2011-01-01

    Secondary metabolite (SM) production by fungi is hypothesized to provide some fitness attribute for the producing organisms. However, most SM clusters are “silent” when fungi are grown in traditional laboratory settings, and it is difficult to ascertain any function or activity of these SM cluster products. Recently, the creation of a chromatin remodeling mutant in Aspergillus nidulans induced activation of several cryptic SM gene clusters. Systematic testing of nine purified metabolites from this mutant identified an emodin derivate with efficacy against both human fungal pathogens (inhibiting both spore germination and hyphal growth) and several bacteria. The ability of catalase to diminish this antimicrobial activity implicates reactive oxygen species generation, specifically, the generation of hydrogen peroxide, as the mechanism of emodin hydroxyl activity. PMID:21478304

  17. Science Supporting Numeric Nutrient Criteria for Lakes and Their Watersheds: ASynopsis of Research Completed for the US Environmental Protection Agency

    EPA Science Inventory

    Nutrient pollution remains one of the most prevalent causes of water quality impairment in the United States. The U.S. Environmental Protection Agency’s (EPA) approach to addressing the challenge of managing nutrient pollution has included supporting development of numeric...

  18. Constitutively active IRF7/IRF3 fusion protein completely protects swine against Foot-and-Mouth Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) remains one of the most devastating livestock diseases around the world. Several serotype specific vaccine formulations exist but require about 5-7 days to induce protective immunity. Our previous studies have shown that a constitutively active fusion protein of porcine ...

  19. Draft Genome Sequence and Complete Plasmid Sequence of Acinetobacter lwoffii F78, an Isolate with Strong Allergy-Protective Properties.

    PubMed

    Fritzenwanker, Moritz; Hain, Torsten; Kesper, Dörthe A; Harb, Hani; Renz, Harald; Domann, Eugen

    2016-01-01

    The hygiene hypothesis states that the tremendous increase in atopic diseases correlates significantly with less contact to microbes in childhood. Here, we report the draft genome sequence of Acinetobacter lwoffii F78, a rural cowshed isolate with strong allergy-protective properties that contains an 8,579-bp plasmid. PMID:27445377

  20. Draft Genome Sequence and Complete Plasmid Sequence of Acinetobacter lwoffii F78, an Isolate with Strong Allergy-Protective Properties

    PubMed Central

    Fritzenwanker, Moritz; Hain, Torsten; Kesper, Dörthe A.; Harb, Hani; Renz, Harald

    2016-01-01

    The hygiene hypothesis states that the tremendous increase in atopic diseases correlates significantly with less contact to microbes in childhood. Here, we report the draft genome sequence of Acinetobacter lwoffii F78, a rural cowshed isolate with strong allergy-protective properties that contains an 8,579-bp plasmid. PMID:27445377

  1. Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses

    PubMed Central

    Frei, Julia C.; Nyakatura, Elisabeth K.; Zak, Samantha E.; Bakken, Russell R.; Chandran, Kartik; Dye, John M.; Lai, Jonathan R.

    2016-01-01

    Filoviruses (Ebola and Marburg) cause severe hemorrhagic fever. There are five species of ebolavirus; among these, the Ebola (Zaire) and Sudan viruses (EBOV and SUDV, respectively) are highly pathogenic and have both caused recurring, large outbreaks. However, the EBOV and SUDV glycoprotein (GP) sequences are 45% divergent and thus antigenically distinct. Few antibodies with cross-neutralizing properties have been described to date. We used antibody engineering to develop novel bispecific antibodies (Bis-mAbs) that are cross-reactive toward base epitopes on GP from EBOV and SUDV. These Bis-mAbs exhibit potent neutralization against EBOV and SUDV GP pseudotyped viruses as well as authentic pathogens, and confer a high degree (in one case 100%) post-exposure protection of mice from both viruses. Our studies show that a single agent that targets the GP base epitopes is sufficient for protection in mice; such agents could be included in panfilovirus therapeutic antibody cocktails. PMID:26758505

  2. Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses.

    PubMed

    Frei, Julia C; Nyakatura, Elisabeth K; Zak, Samantha E; Bakken, Russell R; Chandran, Kartik; Dye, John M; Lai, Jonathan R

    2016-01-01

    Filoviruses (Ebola and Marburg) cause severe hemorrhagic fever. There are five species of ebolavirus; among these, the Ebola (Zaire) and Sudan viruses (EBOV and SUDV, respectively) are highly pathogenic and have both caused recurring, large outbreaks. However, the EBOV and SUDV glycoprotein (GP) sequences are 45% divergent and thus antigenically distinct. Few antibodies with cross-neutralizing properties have been described to date. We used antibody engineering to develop novel bispecific antibodies (Bis-mAbs) that are cross-reactive toward base epitopes on GP from EBOV and SUDV. These Bis-mAbs exhibit potent neutralization against EBOV and SUDV GP pseudotyped viruses as well as authentic pathogens, and confer a high degree (in one case 100%) post-exposure protection of mice from both viruses. Our studies show that a single agent that targets the GP base epitopes is sufficient for protection in mice; such agents could be included in panfilovirus therapeutic antibody cocktails. PMID:26758505

  3. IMPIPS: The Immune Protection-Inducing Protein Structure Concept in the Search for Steric-Electron and Topochemical Principles for Complete Fully-Protective Chemically Synthesised Vaccine Development

    PubMed Central

    Patarroyo, Manuel Elkin; Bermúdez, Adriana; Alba, Martha Patricia; Vanegas, Magnolia; Moreno-Vranich, Armando; Poloche, Luis Antonio; Patarroyo, Manuel Alfonso

    2015-01-01

    Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind. PMID:25879751

  4. IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.

    PubMed

    Patarroyo, Manuel Elkin; Bermúdez, Adriana; Alba, Martha Patricia; Vanegas, Magnolia; Moreno-Vranich, Armando; Poloche, Luis Antonio; Patarroyo, Manuel Alfonso

    2015-01-01

    Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind. PMID:25879751

  5. Secondary Buruli Ulcer Skin Lesions Emerging Several Months after Completion of Chemotherapy: Paradoxical Reaction or Evidence for Immune Protection?

    PubMed Central

    Ruf, Marie-Thérèse; Chauty, Annick; Adeye, Ambroise; Ardant, Marie-Françoise; Koussemou, Hugues; Johnson, Roch Christian; Pluschke, Gerd

    2011-01-01

    Background The neglected tropical disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic ulcerative skin lesions. Histopathological features are progressive tissue necrosis, extracellular clusters of acid fast bacilli (AFB) and poor inflammatory responses at the site of infection. After the recommended eight weeks standard treatment with rifampicin and streptomycin, a reversal of the local immunosuppression caused by the macrolide toxin mycolactone of M. ulcerans is observed. Methodology/Principal Findings We have conducted a detailed histopathological and immunohistochemical analysis of tissue specimens from two patients developing multiple new skin lesions 12 to 409 days after completion of antibiotic treatment. Lesions exhibited characteristic histopathological hallmarks of Buruli ulcer and AFB with degenerated appearance were found in several of them. However, other than in active disease, lesions contained massive leukocyte infiltrates including large B-cell clusters, as typically found in cured lesions. Conclusion/Significance Our histopathological findings demonstrate that the skin lesions emerging several months after completion of antibiotic treatment were associated with M. ulcerans infection. During antibiotic therapy of Buruli ulcer development of new skin lesions may be caused by immune response-mediated paradoxical reactions. These seem to be triggered by mycobacterial antigens and immunostimulators released from clinically unrecognized bacterial foci. However, in particular the lesions that appeared more than one year after completion of antibiotic treatment may have been associated with new infection foci resolved by immune responses primed by the successful treatment of the initial lesion. PMID:21829740

  6. Aspergillus fumigatus and Aspergillosis

    PubMed Central

    Latgé, Jean-Paul

    1999-01-01

    Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy. PMID:10194462

  7. Genomics of Aspergillus flavus mycotoxin production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aspergilli show immense ecological and metabolic diversity. To date, the sequences of fifteen different Aspergillus genomes have been determined providing scientists with an exciting resource to improve the understanding of Aspergillus molecular genomics. Aspergillus flavus, one of the most wide...

  8. Rabies-virus-glycoprotein-pseudotyped recombinant baculovirus vaccine confers complete protection against lethal rabies virus challenge in a mouse model.

    PubMed

    Wu, Qunfeng; Yu, Fulai; Xu, Jinfang; Li, Yang; Chen, Huanchun; Xiao, Shaobo; Fu, Zhen F; Fang, Liurong

    2014-06-25

    Rabies virus has been an ongoing threat to humans and animals. Here, we developed a new strategy to generate a rabies virus vaccine based on a pseudotyped baculovirus. The recombinant baculovirus (BV-RVG/RVG) was pseudotyped with the rabies virus glycoprotein (RVG) and also simultaneously expressed another RVG under the control of the immediate early CMV promoter. In vitro, this RVG-pseudotyped baculovirus vector induced syncytium formation in insect cells and displayed more efficient gene delivery into mammalian cells. Mice immunized with BV-RVG/RVG developed higher levels of virus-neutralizing antibodies, and conferred 100% protection against rabies viral challenge. These data indicate that the RVG-pseudotyped baculovirus BV-RVG/RVG can be used as an alternative strategy to develop a safe and efficacious vaccine against the rabies virus. PMID:24793501

  9. Piglets with maternally derived antibodies from sows immunized with rAdV-SFV-E2 were completely protected against lethal CSFV challenge.

    PubMed

    Xia, Shui-Li; Du, Mingliang; Lei, Jian-Lin; Liu, Yan; Wang, Yimin; Ji, Shengwei; Xiang, Guang-Tao; Li, Lian-Feng; Cong, Xin; Luo, Yuzi; Shao, Lina; Qiu, Hua-Ji; Sun, Yuan

    2016-07-15

    Classical swine fever (CSF) is an economically important infectious disease of pigs caused by Classical swine fever virus (CSFV). To facilitate the eradication of CSF in endemic areas, a marker vaccine enabling differentiation of infected from vaccinated animals (DIVA) is urgently needed. Previously, we have demonstrated that the DIVA vaccine rAdV-SFV-E2, an adenovirus-vectored Semliki Forest virus replicon expressing the E2 glycoprotein of CSFV, induces complete protection from lethal CSFV challenge. The aim of this study was to investigate whether maternally derived antibodies (MDAs) from sows immunized with rAdV-SFV-E2 can effectively protect piglets against lethal CSFV challenge. Three groups of five-week-old piglets (n=4), with or without MDAs, were challenged with the highly virulent CSFV Shimen strain. Clinical signs, CSFV-specific antibodies, viremia and pathological and histopathological changes were monitored. The results showed that the piglets with MDAs from the sow immunized with rAdV-SFV-E2 were protected clinically, virologically and pathologically, while the piglets with undetectable MDAs from the rAdV-SFV-E2-immunized sow were partially protected (2/4 survival), in contrast with the piglets from the non-vaccinated sow, which displayed CSF-typical clinical signs, viremia, deaths (4/4) and pathological/histopathological lesions. These results indicate that MDAs from the sow immunized with rAdV-SFV-E2 are able to confer full passive immunity to newborn piglets. PMID:27283854

  10. Vaccination of horses with a recombinant modified vaccinia Ankara virus (MVA) expressing African horse sickness (AHS) virus major capsid protein VP2 provides complete clinical protection against challenge

    PubMed Central

    Alberca, Berta; Bachanek-Bankowska, Katarzyna; Cabana, Marta; Calvo-Pinilla, Eva; Viaplana, Elisenda; Frost, Lorraine; Gubbins, Simon; Urniza, Alicia; Mertens, Peter; Castillo-Olivares, Javier

    2014-01-01

    African horse sickness virus (AHSV) is an arthropod-borne pathogen that infects all species of equidae and causes high mortality in horses. Previously, a recombinant modified vaccinia Ankara (MVA) virus expressing the protein VP2 of AHSV serotype 4 was shown to induce virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR −/−) against virulent AHSV challenge. This study builds on the previous work, examining the protective efficacy of MVA-VP2 vaccination in the natural host of AHSV infection. A study group of 4 horses was vaccinated twice with a recombinant MVA virus expressing the major capsid protein (VP2) of AHSV serotype 9. Vaccinated animals and a control group of unvaccinated horses were then challenged with a virulent strain of AHSV-9. The vaccinated animals were completely protected against clinical disease and also against viraemia as measured by standard end-point dilution assays. In contrast, all control horses presented viraemia after challenge and succumbed to the infection. These results demonstrate the potential of recombinant MVA viruses expressing the outer capsid VP2 of AHSV as a protective vaccine against AHSV infection in the field. PMID:24837765

  11. A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice

    PubMed Central

    2011-01-01

    Background Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. Results The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. Conclusion BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection. PMID:21639929

  12. Evaluation of Protective Efficacy of Avicennia marina (Forssk.) Vierh Leaves against Complete Freund᾽s Adjuvant-induced Arthritis in Wistar

    PubMed Central

    Zamani Gandomani, Mahdi; Forouzandeh Malati, Elaheh

    2014-01-01

    Aviecennia marina (Avicenniaceae) is an endemic plant that widely distributed in the Southern parts of Iran. This plant has been used as treatment of rheumatism arthritis among the inhabitants of Southern parts of Iran. The Avicennia marina hydroalcoholic extract was prepared and its protective efficacy was investigated using measurement of ankle diameter, total WBC and RBC count, ESR, and Pro-inflammatory cytokines levels in the complete Freund᾽s adjuvant (CFA)-induced arthritic rat. The increment in ESR and total WBC, reduction in RBC count and hemoglobin levels observed in the arthritic animals were also found to be significantly restored in HEA treated rats. A. marina at 400 mg/Kg significantly decreases the serum pro-inflammatory cytokines as well as normalizes ankle diameter of CFA rats. A. marina (400 mg/Kg) significantly normalizes changes observed in arthritic rats to near normal conditions, indicates that A. marina has promising protective efficacy against arthritic rats. PMID:25276195

  13. Rabies DNA vaccine encoding lysosome-targeted glycoprotein supplemented with Emulsigen-D confers complete protection in preexposure and postexposure studies in BALB/c mice.

    PubMed

    Kaur, Manpreet; Saxena, Ankur; Rai, Anant; Bhatnagar, Rakesh

    2010-01-01

    The worldwide incidence of rabies and the inability of currently used vaccination strategies to provide highly potent and cost-effective therapy indicate the need for an improved rabies vaccine. Thus, DNA vaccine based on lysosome-targeted glycoprotein of the rabies virus was evaluated in BALB/c mice. It imparted partial protection (60%) against challenge with 20 LD(50) of the challenge virus standard (CVS) strain of rabies virus. To improve the outcome of vaccination, to ultimately enhance the immune response, we investigated different routes for DNA vaccine delivery, varied doses of DNA, and the influence of adjuvant supplementation. The highest immune response pertaining to IgG antibody titer, with a predominantly IgG1/IgG2a subclass distribution, effective cellular immunity, and a high level of rabies virus neutralizing antibodies (RVNAs) was attained by the optimized DNA vaccine formulation comprising intramuscular administration of 100 microg of DNA vaccine supplemented with Emulsigen-D. In preexposure prophylaxis, a 3-dose regimen of this formulation generated a high RVNA titer (32 IU/ml) and conferred complete protection against challenge with 20 LD(50) of CVS. For postexposure efficacy analysis, rabies was experimentally induced with 50 LD(50) of CVS. Subsequent therapy with 5 doses of the formulation completely prevented rabies in BALB/c mice, which maintained protective RVNA titers of 4 IU/ml. The World Health Organization recommended rabies protective titer threshold is 0.5 IU/ml. Thus, this optimized DNA vaccine formulation provides an avenue for preventing and controlling rabies. PMID:19741168

  14. Cyclopiazonic Acid Biosynthesis of Aspergillus flavus and Aspergillus oryzae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by some of the same strains of A. flavus that produce aflatoxins and by some Aspergillus oryzae strains. Despite its discovery 40 years ago, few reviews of its toxicity and biosynthesis have been reported. This review examines w...

  15. A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks ▿ † §

    PubMed Central

    Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Wu, Li; Zeng, Xianying; Tian, Guobin; Ge, Jinying; Kawaoka, Yoshihiro; Bu, Zhigao; Chen, Hualan

    2011-01-01

    Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 106 PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks. PMID:21865383

  16. Bean α-amylase inhibitor 1 in transgenic peas (Pisum sativum) provides complete protection from pea weevil (Bruchus pisorum) under field conditions

    PubMed Central

    Morton, Roger L.; Schroeder, Hart E.; Bateman, Kaye S.; Chrispeels, Maarten J.; Armstrong, Eric; Higgins, Thomas J. V.

    2000-01-01

    Two α-amylase inhibitors, called αAI-1 and αAI-2, that share 78% amino acid sequence identity and have a differential specificity toward mammalian and insect α-amylases are present in different accessions of the common bean (Phaseolus vulgaris). Using greenhouse-grown transgenic peas (Pisum sativum), we have shown previously that expression of αAI-1 in pea seeds can provide complete protection against the pea weevil (Bruchus pisorum). Here, we report that αAI-1 also protects peas from the weevil under field conditions. The high degree of protection is explained by our finding that αAI-1 inhibits pea bruchid α-amylase by 80% over a broad pH range (pH 4.5–6.5). αAI-2, on the other hand, is a much less effective inhibitor of pea bruchid α-amylase, inhibiting the enzyme by only 40%, and only in the pH 4.0–4.5 range. Nevertheless, this inhibitor was still partially effective in protecting field-grown transgenic peas against pea weevils. The primary effect of αAI-2 appeared to be a delay in the maturation of the larvae. This contrasts with the effect of αAI-1, which results in larval mortality at the first or second instar. These results are discussed in relationship to the use of amylase inhibitors with different specificities to bring about protection of crops from their insect pests or to decrease insect pest populations below the economic injury level. PMID:10759552

  17. Aspergillus infections in cystic fibrosis.

    PubMed

    King, Jill; Brunel, Shan F; Warris, Adilia

    2016-07-01

    Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains the commonest cause of death and accounts for over 90% of mortality. Bacteria as Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex have been regarded the main CF pathogens and their role in progressive lung decline has been studied extensively. Little attention has been paid to the role of Aspergillus spp. and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory disease in CF, despite their frequent recovery in respiratory samples. It has become more apparent however, that Aspergillus spp. may play an important role in chronic lung disease in CF. Research delineating the underlying mechanisms of Aspergillus persistence and infection in the CF lung and its link to lung deterioration is lacking. This review summarizes the Aspergillus disease phenotypes observed in CF, discusses the role of CFTR (cystic fibrosis transmembrane conductance regulator)-protein in innate immune responses and new treatment modalities. PMID:27177733

  18. Sexual recombination in Aspergillus tubingensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus tubingensis from section Nigri (Black Aspergilli) is closely related to A. niger and is used extensively in the industrial production of enzymes and organic acids. We recently discovered sexual reproduction in A. tubingensis and in this study, demonstrate that the progeny are products o...

  19. Sexual reproduction in Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus is the major producer of carcinogenic aflatoxins in crops worldwide and is also an important opportunistic human pathogen in aspergillosis. The sexual state of this heterothallic fungus is described from crosses between strains of the opposite mating type. Sexual reproduction oc...

  20. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  1. Aspergillus: a primer for the novice.

    PubMed

    Bennett, J W

    2009-01-01

    Aspergillus is a genus of molds named after the morphological structure that bears asexual spores, the aspergillum, which resembles a liturgical device. This genus contains several species of positive or negative economic importance in industry, agriculture and medicine. The majority of aspergilli, including most species of economic importance, are known to reproduce only by asexual spores. Genome projects have been completed for A. fumigatus, A. nidulans, A. niger and A. oryzae; several other species are also being sequenced. The data from these genome projects have been useful in elucidating aspects of phylogeny, the evolution of sexuality and the extent of secondary metabolite diversity. To date, however, the impact on drug discovery, diagnosis of aspergillosis, and our understanding of fungal pathogenesis has been less pronounced. PMID:19253144

  2. Gauche(+) side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine.

    PubMed

    Bermúdez, Adriana; Calderon, Dayana; Moreno-Vranich, Armando; Almonacid, Hannia; Patarroyo, Manuel A; Poloche, Andrés; Patarroyo, Manuel E

    2014-04-11

    Topological and stereo-electron characteristics are essential in major histocompability class II-peptide-T-cell receptor (MHC-p-TCR) complex formation for inducing an appropriate immune response. Modified high activity binding peptides (mHABPs) were synthesised for complete full protection antimalarial vaccine development producing a large panel of individually fully protection-inducing protein structures (FPIPS) and very high long-lasting antibody-inducing (VHLLAI) mHABPs. Most of those which did not interfere, compete, inhibit or suppress their individual VHLLAI or FPIPS activity contained or displayed a polyproline II-like (PPIIL) structure when mixed. Here we show that amino acid side-chains located in peptide binding region (PBR) positions p3 and p7 displayed specific electron charges and side-chain gauche(+) orientation for interacting with the TCR. Based on the above, and previously described physicochemical principles, non-interfering, long-lasting, full protection-inducing, multi-epitope, multistage, minimal subunit-based chemically synthesised mHABP mixtures can be designed for developing vaccines against diseases scourging humankind, malaria being one of them. PMID:24582630

  3. Aspergillus asperus and Aspergillus collinsii, two new species from Aspergillus section Usti

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In sampling fungi from the built environment, two isolates that could not confidently be placed in described species were encountered. Phenotypic analysis suggested that they belonged in Aspergillus sect. Usti. In order to verify the sectional placement and to assure that they were undescribed rathe...

  4. Atypical Aspergillus parasiticus isolates from pistachio with aflR gene nucleotide insertion identical to Aspergillus sojae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxins are the most toxic and carcinogenic secondary metabolites produced primarily by the filamentous fungi Aspergillus flavus and Aspergillus parasiticus. The toxins cause devastating economic losses because of strict regulations on distribution of contaminated products. Aspergillus sojae are...

  5. Environmental assessment and finding of no significant impact for completion of flood protection works, Bannister Road Federal Complex, Kansas City, Missouri

    SciTech Connect

    Not Available

    1991-09-18

    The Department of Energy (DOE) proposes to provide partial funding to the Corps of Engineers (COE) for the completion of the flood protection works at the Bannister Road Federal Complex in Kansas City, Missouri. The DOE Kansas City Plant is a major tenant of the Complex. COE has prepared an environmental assessment (EA) for the project which includes the construction of levees, floodwalls, and drainage ditches. DOE has adopted the EA prepared by COE (DOE/EA-0509), this report. Based on the analyses in this EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969, 42 USC 4321 et seq. Therefore, the preparation of an environmental impact statement is not required, and DOE is issuing this Finding of No Significant Impact (FONSI).

  6. Newcastle Disease Virus-Based Live Attenuated Vaccine Completely Protects Chickens and Mice from Lethal Challenge of Homologous and Heterologous H5N1 Avian Influenza Viruses▿

    PubMed Central

    Ge, Jinying; Deng, Guohua; Wen, Zhiyuan; Tian, Guobing; Wang, Yong; Shi, Jianzhong; Wang, Xijun; Li, Yanbing; Hu, Sen; Jiang, Yongping; Yang, Chinglai; Yu, Kangzhen; Bu, Zhigao; Chen, Hualan

    2007-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease virus (NDV), however, have been used successfully to easily vaccinate large numbers of animals. In this study, we used reverse genetics to construct a NDV that expressed an H5 subtype avian influenza virus (AIV) hemagglutinin (HA). Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (H5N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain. The recombinant viruses stably expressing the wild-type and mutant HA genes were found to be innocuous after intracerebral inoculation of 1-day-old chickens. A single dose of the recombinant viruses in chickens induced both NDV- and AIV H5-specific antibodies and completely protected chickens from challenge with a lethal dose of both velogenic NDV and homologous and heterologous H5N1 HPAIV. In addition, BALB/c mice immunized with the recombinant NDV-based vaccine produced H5 AIV-specific antibodies and were completely protected from homologous and heterologous lethal virus challenge. Our results indicate that recombinant NDV is suitable as a bivalent live attenuated vaccine against both NDV and AIV infection in poultry. The recombinant NDV vaccine may also have potential use in high-risk human individuals to control the pandemic spread of lethal avian influenza. PMID:17050610

  7. Galactosaminogalactan, a New Immunosuppressive Polysaccharide of Aspergillus fumigatus

    PubMed Central

    Simenel, Catherine; Coddeville, Bernadette; van Vliet, Sandra J.; van Kooyk, Yvette; Bozza, Silvia; Moretti, Silvia; Schwarz, Flavio; Trichot, Coline; Aebi, Markus; Delepierre, Muriel; Elbim, Carole; Romani, Luigina; Latgé, Jean-Paul

    2011-01-01

    A new polysaccharide secreted by the human opportunistic fungal pathogen Aspergillus fumigatus has been characterized. Carbohydrate analysis using specific chemical degradations, mass spectrometry, 1H and 13C nuclear magnetic resonance showed that this polysaccharide is a linear heterogeneous galactosaminogalactan composed of α1-4 linked galactose and α1-4 linked N-acetylgalactosamine residues where both monosacharides are randomly distributed and where the percentage of galactose per chain varied from 15 to 60%. This polysaccharide is antigenic and is recognized by a majority of the human population irrespectively of the occurrence of an Aspergillus infection. GalNAc oligosaccharides are an essential epitope of the galactosaminogalactan that explains the universal antibody reaction due to cross reactivity with other antigenic molecules containing GalNAc stretches such as the N-glycans of Campylobacter jejuni. The galactosaminogalactan has no protective effect during Aspergillus infections. Most importantly, the polysaccharide promotes fungal development in immunocompetent mice due to its immunosuppressive activity associated with disminished neutrophil infiltrates. PMID:22102815

  8. Cyclopiazonic Acid Biosynthesis of Aspergillus flavus and Aspergillus oryzae

    PubMed Central

    Chang, Perng-Kuang; Ehrlich, Kenneth C.; Fujii, Isao

    2009-01-01

    Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by some of the same strains of A. flavus that produce aflatoxins and by some Aspergillus oryzae strains. Despite its discovery 40 years ago, few reviews of its toxicity and biosynthesis have been reported. This review examines what is currently known about the toxicity of CPA to animals and humans, both by itself or in combination with other mycotoxins. The review also discusses CPA biosynthesis and the genetic diversity of CPA production in A. flavus/oryzae populations. PMID:22069533

  9. Two novel species of Aspergillus section Nigri from indoor air

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus collinsii, Aspergillus floridensis, and Aspergillus trinidadensis are described as novel uniseriate species of Aspergillus section Nigri isolated from air samples. To describe the species we used phenotypes from 7-d Czapek yeast extract agar culture (CYA) and malt extract agar culture (M...

  10. Conserved Secondary Structures in Aspergillus

    PubMed Central

    McGuire, Abigail Manson; Galagan, James E.

    2008-01-01

    Background Recent evidence suggests that the number and variety of functional RNAs (ncRNAs as well as cis-acting RNA elements within mRNAs ) is much higher than previously thought; thus, the ability to computationally predict and analyze RNAs has taken on new importance. We have computationally studied the secondary structures in an alignment of six Aspergillus genomes. Little is known about the RNAs present in this set of fungi, and this diverse set of genomes has an optimal level of sequence conservation for observing the correlated evolution of base-pairs seen in RNAs. Methodology/Principal Findings We report the results of a whole-genome search for evolutionarily conserved secondary structures, as well as the results of clustering these predicted secondary structures by structural similarity. We find a total of 7450 predicted secondary structures, including a new predicted ∼60 bp long hairpin motif found primarily inside introns. We find no evidence for microRNAs. Different types of genomic regions are over-represented in different classes of predicted secondary structures. Exons contain the longest motifs (primarily long, branched hairpins), 5′ UTRs primarily contain groupings of short hairpins located near the start codon, and 3′ UTRs contain very little secondary structure compared to other regions. There is a large concentration of short hairpins just inside the boundaries of exons. The density of predicted intronic RNAs increases with the length of introns, and the density of predicted secondary structures within mRNA coding regions increases with the number of introns in a gene. Conclusions/Sigificance There are many conserved, high-confidence RNAs of unknown function in these Aspergillus genomes, as well as interesting spatial distributions of predicted secondary structures. This study increases our knowledge of secondary structure in these aspergillus organisms. PMID:18665251

  11. Aspergillus Osteomyelitis of the Skull.

    PubMed

    Nicholson, Simon; King, Richard; Chumas, Paul; Russell, John; Liddington, Mark

    2016-07-01

    Osteomyelitis of the craniofacial skeleton is rare, with fungal pathogens least commonly implicated. The authors present 2 patients of osteomyelitis of the skull caused by Aspergillus spp. and discuss the diagnosis, clinicopathological course, and management strategies.Late recurrence seen in this type of infection warrants long-term follow-up and a high index of suspicion for the clinical signs associated with recurrence.Such patients would benefit from their surgical debridement being planned and managed via a specialist craniofacial unit, so as to utilize the most aesthetically sensitive approach and the experience of specialists from several surgical disciplines. PMID:27391523

  12. A sindbis virus replicon-based DNA vaccine encoding the rabies virus glycoprotein elicits immune responses and complete protection in mice from lethal challenge.

    PubMed

    Saxena, Sonal; Dahiya, Shyam S; Sonwane, Arvind A; Patel, Chhabi Lal; Saini, Mohini; Rai, A; Gupta, Praveen K

    2008-12-01

    A sindbis virus replicon-based DNA vaccine encoding rabies virus glycoprotein (G) was developed by subcloning rabies G gene into a sindbis virus replicon-based vaccine vector (pAlpha). The self-amplification of RNA transcripts and translation efficiency of rabies G was analyzed in pAlpha-Rab-G-transfected mammalian cells using RT-PCR, SDS-PAGE and Western blot analysis. The transfected cells also showed induction of apoptosis which is an important event in the enhancement of immune responses. Further, immune responses induced with replicon-based rabies DNA vaccine (pAlpha-Rab-G) was compared with conventional rabies DNA vaccine and commercial cell culture vaccine (Rabipur) in intramuscularly injected mice. The mice immunized with replicon-based rabies DNA vaccine induced humoral and cell mediated immune responses better than conventional rabies DNA vaccine however, comparable to Rabipur vaccine. On challenge with rabies virus CVS strain, replicon-based rabies DNA vaccine conferred complete protection similar to Rabipur. These results demonstrate that replicon-based rabies DNA vaccine is effective in inducing both humoral and cellular immune responses and can be considered as effective vaccine against rabies. PMID:18848857

  13. Protective effect of apigenin on Freund's complete adjuvant-induced arthritis in rats via inhibiting P2X7/NF-κB pathway.

    PubMed

    Chang, Xiayun; He, He; Zhu, Lingpeng; Gao, Jin; Wei, Tingting; Ma, Zhanqian; Yan, Tianhua

    2015-07-01

    To evaluate the effect of apigenin (AP) on arthritis in rats stimulated by Freund's complete adjuvant (FCA) was the main purpose of the investigation. Arthritis model was established by the administration of 0.1 ml FCA in the palmar surface. AP and diclofenac sodium (DS) were administered to explore and evidence the protective effects against adjuvant-induced arthritis (AA). Cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were detected to assess the anti-inflammatory effect of AP. Besides, pathological conditions were examined in rat paws. Related-proteins of nuclear factor kappa B (NF-κB) signal pathway activated by P2X7 were investigated to determine the molecular mechanism of AP and their expressions were measured by western blot. The data showed that AP significantly suppressed the expressions of P2X7/NF-κB signal-related proteins and alleviated inflammatory reactions. Therefore, it was assumed that AP might be a potential therapeutic candidate to treat arthritis. PMID:25935278

  14. The growing promise of Toll-deficient Drosophila melanogaster as a model for studying Aspergillus pathogenesis and treatment.

    PubMed

    Lionakis, Michail S; Kontoyiannis, Dimitrios P

    2010-01-01

    Despite considerable progress over recent years, the prognosis of invasive aspergillosis (IA) remains unfavorable, reflecting an incomplete understanding of Aspergillus pathogenesis and suboptimal antifungal efficacy in vivo. Mammalian host systems including rodents and rabbits are important tools in elucidating antifungal drug activity and the immunopathogenesis of IA. Nonetheless, they are hampered by limitations that impose a "bottleneck" in mass screening of novel antifungal compounds and putative Aspergillus virulence factors including their cost, labor intensity and ethical constraints. Drosophila melanogaster is an invertebrate host with a long tract record of genetic studies and a simple, yet highly conserved innate immune system. Herein, we describe our experience using this fly model as a facile, non-laborious, inexpensive pathosystem for high-throughput screening of novel antifungal compounds and putative Aspergillus mutants, and studying antifungal innate immunity. We present three infection protocols (i.e., injection, rolling, ingestion) that introduce Aspergillus either directly into the hemolymph or at different epithelial surfaces of Toll-deficient Drosophila flies. As a proof of principle, we demonstrate attenuated virulence of known hypovirulent Aspergillus strains and protection of Aspergillus-infected flies given oral Aspergillus-active agents such is voriconazole. These protocols can be adapted for similar studies of other fungal pathogens. Crossing and generation of Toll-deficient Drosophila flies takes 3 weeks; Aspergillus conidial preparation takes 3 days; fly inoculation depending on the infection assay takes 1 to 6-8 hours; and assessment of fly survival, Aspergillus strain virulence, Drosophila innate host parameters and/or drug activity takes 4-8 days. PMID:21178494

  15. NITRIFICATION BY ASPERGILLUS FLAVUS1

    PubMed Central

    Marshall, K. C.; Alexander, M.

    1962-01-01

    Marshall, K. C. (Cornell University, Ithaca, N. Y.) and M. Alexander. Nitrification by Aspergillus flavus. J. Bacteriol. 83:572–578. 1962.—Aspergillus flavus has been shown to produce bound hydroxylamine, nitrite, and nitrate when grown in peptone, amino acid, or buffered ammonium media. Free hydroxylamine was not detected in these cultures, but it was found in an unbuffered ammonium medium in which neither nitrite nor nitrate was formed. Evidence was obtained for the presence of β-nitropropionic acid in the filtrate of an actively nitrifying culture. Alumina treatment of an ammonium medium prevented the formation by growing cultures of nitrite and nitrate but not bound hydroxylamine. The effect of alumina treatment was reversed by the addition of 10−3m CeCl3 to the medium. Extracts of the fungus contained peroxidase and an enzyme capable of catalyzing the production of nitrite from β-nitropropionic acid. The nitrite-forming enzyme is apparently specific for β-nitropropionate; no activity was found with nitromethane, nitroethane, and nitropropane as substrates. Nitrate was not reduced to nitrite nor was nitrite oxidized to nitrate by the hyphal extracts. The significance of these observations in nitrification by A. flavus is discussed. PMID:14470254

  16. CADRE: the Central Aspergillus Data REpository 2012.

    PubMed

    Mabey Gilsenan, Jane; Cooley, John; Bowyer, Paul

    2012-01-01

    The Central Aspergillus Data REpository (CADRE; http://www.cadre-genomes.org.uk) is a public resource for genomic data extracted from species of Aspergillus. It provides an array of online tools for searching and visualising features of this significant fungal genus. CADRE arose from a need within the medical community to understand the human pathogen Aspergillus fumigatus. Due to the paucity of Aspergillus genomic resources 10 years ago, the long-term goal of this project was to collate and maintain Aspergillus genomes as they became available. Since our first release in 2004, the resource has expanded to encompass annotated sequence for eight other Aspergilli and provides much needed support to the international Aspergillus research community. Recent developments, however, in sequencing technology are creating a vast amount of genomic data and, as a result, we shortly expect a tidal wave of Aspergillus data. In preparation for this, we have upgraded the database and software suite. This not only enables better management of more complex data sets, but also improves annotation by providing access to genome comparison data and the integration of high-throughput data. PMID:22080563

  17. Secondary metabolite profiles and antifungal drug susceptibility of Aspergillus fumigatus and closely related species, Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans.

    PubMed

    Tamiya, Hiroyuki; Ochiai, Eri; Kikuchi, Kazuyo; Yahiro, Maki; Toyotome, Takahito; Watanabe, Akira; Yaguchi, Takashi; Kamei, Katsuhiko

    2015-05-01

    The incidence of Aspergillus infection has been increasing in the past few years. Also, new Aspergillus fumigatus-related species, namely Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans, were shown to infect humans. These fungi exhibit marked morphological similarities to A. fumigatus, albeit with different clinical courses and antifungal drug susceptibilities. The present study used liquid chromatography/time-of-flight mass spectrometry to identify the secondary metabolites secreted as virulence factors by these Aspergillus species and compared their antifungal susceptibility. The metabolite profiles varied widely among A. fumigatus, A. lentulus, A. udagawae, and A. viridinutans, producing 27, 13, 8, and 11 substances, respectively. Among the mycotoxins, fumifungin, fumiquinazoline A/B and D, fumitremorgin B, gliotoxin, sphingofungins, pseurotins, and verruculogen were only found in A. fumigatus, whereas auranthine was only found in A. lentulus. The amount of gliotoxin, one of the most abundant mycotoxins in A. fumigatus, was negligible in these related species. In addition, they had decreased susceptibility to antifungal agents such as itraconazole and voriconazole, even though metabolites that were shared in the isolates showing higher minimum inhibitory concentrations than epidemiological cutoff values were not detected. These strikingly different secondary metabolite profiles may lead to the development of more discriminative identification protocols for such closely related Aspergillus species as well as improved treatment outcomes. PMID:25737146

  18. Isolation and identification of nematode-antagonistic compounds from the fungus Aspergillus candidus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An isolate of the fungus Aspergillus candidus was tested for production of nematicidal compounds. Adults of the nematode Ditylenchus destructor were completely inactive after 24 hr exposure to soy medium in which A. candidus was cultured. Column, thin layer and preparative chromatographies, and spec...

  19. Genetic diversity of Aspergillus species isolated from onychomycosis and Aspergillus hongkongensis sp. nov., with implications to antifungal susceptibility testing.

    PubMed

    Tsang, Chi-Ching; Hui, Teresa W S; Lee, Kim-Chung; Chen, Jonathan H K; Ngan, Antonio H Y; Tam, Emily W T; Chan, Jasper F W; Wu, Andrea L; Cheung, Mei; Tse, Brian P H; Wu, Alan K L; Lai, Christopher K C; Tsang, Dominic N C; Que, Tak-Lun; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2016-02-01

    Thirteen Aspergillus isolates recovered from nails of 13 patients (fingernails, n=2; toenails, n=11) with onychomycosis were characterized. Twelve strains were identified by multilocus sequencing as Aspergillus spp. (Aspergillus sydowii [n=4], Aspergillus welwitschiae [n=3], Aspergillus terreus [n=2], Aspergillus flavus [n=1], Aspergillus tubingensis [n=1], and Aspergillus unguis [n=1]). Isolates of A. terreus, A. flavus, and A. unguis were also identifiable by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The 13th isolate (HKU49(T)) possessed unique morphological characteristics different from other Aspergillus spp. Molecular characterization also unambiguously showed that HKU49(T) was distinct from other Aspergillus spp. We propose the novel species Aspergillus hongkongensis to describe this previously unknown fungus. Antifungal susceptibility testing showed most Aspergillus isolates had low MICs against itraconazole and voriconazole, but all Aspergillus isolates had high MICs against fluconazole. A diverse spectrum of Aspergillus species is associated with onychomycosis. Itraconazole and voriconazole are probably better drug options for Aspergillus onychomycosis. PMID:26658315

  20. Degradation of melanin by Aspergillus fumigatus.

    PubMed Central

    Luther, J P; Lipke, H

    1980-01-01

    A strain of Aspergillus fumigatus from composted coffee and garden wastes utilized natural deproteinized insect, banana, hair, octopus, and synthetic tyrosine and dopa melanins as sole sources of carbon. With a sucrose supplement, degradation was essentially complete after 50 days in Czapek medium pH 6.5 at 30 degrees C. The catabolic rate differed for each substrate pigment, as did the molecular weight distribution of products accumulating in the medium. After incubation with L-[U-14C]melanin, over 50% was recovered in a dark fungal pigment, the remainder appearing as cell protein, chitin, lipid, CO2, and polar metabolites. When grown on melanin, the normally pale mycelia darkened with the production of a fungal allomelanin, with infrared spectrum and alkali fusion products differing from those of the substrate pigment. Isotope distribution in amino acids for A. fumigatus grown on labeled melanin supplemented with sucrose suggested separate pools for synthesis of cell proteins and melanoproteins. Deposition of allomelanin increased resistance of conidia, sterigma, and conidiophores to lytic carbohydrases as judged by scanning electron microscopy. Images PMID:6996615

  1. Fingernail Onychomycosis Due to Aspergillus niger.

    PubMed

    Kim, Dong Min; Suh, Moo Kyu; Ha, Gyoung Yim; Sohng, Seung Hyun

    2012-11-01

    Onychomycosis is usually caused by dermatophytes, but some species of nondermatophytic molds and yeasts are also associated with nail invasion. Aspergillus niger is a nondermatophytic mold which exists as an opportunistic filamentous fungus in all environments. Here, we report a case of onychomycosis caused by A. niger in a 66-year-old female. The patient presented with a black discoloration and a milky white base and onycholysis on the proximal portion of the right thumb nail. Direct microscopic examination of scrapings after potassium hydroxide (KOH) preparation revealed dichotomous septate hyphae. Repeated cultures on Sabouraud's dextrose agar (SDA) without cycloheximide produced the same black velvety colonies. No colony growth occurred on SDA with cycloheximide slants. Biseriate phialides covering the entire vesicle with radiate conidial heads were observed on the slide culture. The DNA sequence of the internal transcribed spacer region of the clinical sample was a 100% match to that of A. niger strain ATCC 16888 (GenBank accession number AY373852). A. niger was confirmed by KOH mount, colony identification, light microscopic morphology, and DNA sequence analysis. The patient was treated orally with 250 mg terbinafine daily and topical amorolfine 5% nail lacquer for 3 months. As a result, the patient was completely cured clinically and mycologically. PMID:23197914

  2. Three new species of Aspergillus section Flavi isolated from almonds and maize in Portugal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three new aflatoxin-producing species belonging to Aspergillus section Flavi are described, Aspergillus mottae, Aspergillus sergii and Aspergillus transmontanensis. These species were isolated from Portuguese almonds and maize. An investigation examining morphology, extrolites and molecular data was...

  3. Characterization of the Aspergillus ochraceoroseus aflatoxin/sterigmatocystin biosynthetic gene cluster

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Production of the carcinogenic aflatoxins has been reported from members of Aspergillus section Flavi, Aspergillus section Nidulantes, and a newly proposed section, Aspergillus section Ochraceorosei that consists of Aspergillus ochraceoroseus and A. rambellii. Unlike members of section Flavi, A. oc...

  4. Aspergillus bronchitis in cystic fibrosis.

    PubMed

    Shoseyov, David; Brownlee, Keith G; Conway, Steven P; Kerem, Eitan

    2006-07-01

    Aspergillus fumigatus, a widely distributed spore-bearing fungus, is commonly grown in sputum cultures of patients with cystic fibrosis (CF). A fumigatus may cause allergic bronchopulmonary aspergillosis (ABPA), a complex condition that leads to worsening of airway inflammation and progressive damage and is diagnosed by specific criteria. In this report, we present six CF patients with respiratory deterioration that did not respond to appropriate antibiotic treatment. All had had A fumigatus in sputum cultures but did not fulfill the criteria of ABPA. Treatment with antifungal agents was followed by improvement in clinical condition. We suggest that in patients with CF, A fumigatus should be considered as a pathogen that may directly cause respiratory exacerbations. Antifungal therapy should be considered when deteriorating respiratory function is not responding to antibacterial therapy and A fumigatus is growing in sputum cultures. PMID:16840406

  5. Aspergillus Infections in Transplant Recipients

    PubMed Central

    Singh, Nina; Paterson, David L.

    2005-01-01

    Aspergillus infections are occurring with an increasing frequency in transplant recipients. Notable changes in the epidemiologic characteristics of this infection have occurred; these include a change in risk factors and later onset of infection. Management of invasive aspergillosis continues to be challenging, and the mortality rate, despite the use of newer antifungal agents, remains unacceptably high. Performing molecular studies to discern new targets for antifungal activity, identifying signaling pathways that may be amenable to immunologic interventions, assessing combination regimens of antifungal agents or combining antifungal agents with modulation of the host defense mechanisms, and devising diagnostic assays that can rapidly and reliably diagnose infections represent areas for future investigations that may lead to further improvement in outcomes. PMID:15653818

  6. Environmental and Developmental Factors Influencing Aflatoxin Production by Aspergillus flavus and Aspergillus parasiticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxins are carcinogenic mycotoxins formed by a number of fungi in the genus Aspergillus. The major fungi responsible for aflatoxin formation in crop seeds in the field and in storage are Aspergillus flavus and A. parasiticus. This review emphasizes developmental, environmental, biological and ...

  7. Recurrent prosthetic valve endocarditis caused by Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus)

    PubMed Central

    Uhrin, Gábor Balázs; Jensen, Rasmus Hare; Korup, Eva; Grønlund, Jens; Hjort, Ulla; Moser, Claus; Arendrup, Maiken Cavling; Schønheyder, Henrik Carl

    2015-01-01

    We report Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus) causing recurrent prosthetic valve endocarditis. The fungus was the sole agent detected during replacement of a mechanical aortic valve conduit due to abscess formation. Despite extensive surgery and anti-fungal treatment, the patient had a cerebral hemorrhage 4 months post-surgery prompting a diagnosis of recurrent prosthetic valve endocarditis and fungemia. PMID:26909244

  8. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins

    PubMed Central

    Gong, An-Dong; Li, He-Ping; Shen, Lu; Zhang, Jing-Bo; Wu, Ai-Bo; He, Wei-Jie; Yuan, Qing-Song; He, Jing-De; Liao, Yu-Cai

    2015-01-01

    Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field. PMID:26500631

  9. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins.

    PubMed

    Gong, An-Dong; Li, He-Ping; Shen, Lu; Zhang, Jing-Bo; Wu, Ai-Bo; He, Wei-Jie; Yuan, Qing-Song; He, Jing-De; Liao, Yu-Cai

    2015-01-01

    Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field. PMID:26500631

  10. Environmental and clinical epidemiology of Aspergillus terreus: data from a prospective surveillance study.

    PubMed

    Rüping, M J G T; Gerlach, S; Fischer, G; Lass-Flörl, C; Hellmich, M; Vehreschild, J J; Cornely, O A

    2011-07-01

    Aspergillus terreus may be resistant to amphotericin B and is associated with significant morbidity and mortality in immunocompromised patients. Local incidence is influenced by the density of airborne Aspergillus spp. spores which may in turn depend on meteorological factors. Once-weekly environmental samples were collected prospectively inside and outside the University Hospital of Cologne, Germany (UHC) and haematological patients were screened for nasal Aspergillus spp. colonisation and monitored for invasive fungal disease (IFD). RAPD (rapid amplification of polymorphic DNA)-polymerase chain reaction (PCR) and amphotericin B susceptibility testing were performed on all A. terreus isolates. A total of 4919 colony-forming units (cfu) were isolated (2212 indoors, 2707 outdoors). Further identification revealed A. fumigatus (73.5%), A. niger (4.3%), A. flavus (1.7%), A. terreus (0.2%) and non-Aspergillus fungi (20.3%). RAPD-PCR did not reveal clonal relationships between the A. terreus isolates. All A. terreus isolates displayed complete resistance to amphotericin. The B. Aspergillus spp. conidia exposure was lowest in June and highest in November inside and outside UHC. Conidia load correlated with the season and the relative humidity, with increasing spore counts during dry periods. One out of 855 nasal swabs was positive for A. niger. The patient did not develop IFD. A. terreus is unlikely to be a relevant pathogen at the UHC. Results from RAPD-PCR suggested a wide epidemiological variety of strains rather than a common source of contamination. Nasal swab surveillance cultures for early detection of Aspergillus spp. colonisation were not useful in identifying patients who may develop IFD. The risk of IFD at the UHC may increase in autumn and during dry periods. PMID:21440331

  11. [Study of the topology of the active center of glycosidases of Aspergillus niger].

    PubMed

    Borzova, N V; Varbanets', L D

    2004-01-01

    Activity of alpha-N-acetylgalactosaminidase and alpha-galactosidase isolated from the culture medium of micromycete Aspergillus niger v. Tiegh F-16694 has been studied as affected by anions, cations and specific chemical reagents (n-chlormercurybenzoate, L-cysteine, dithiotreitol, beta-mercaptoethanol, EDTA, o-phenanthroline, sodium azide, hydrogen peroxide). It has been established that silver ions noncompetitively inhibit alpha-galactosidase at pH 5.2, the inhibition constant (Ki) being 2.5 x 10(-4) M. Galactose in concentration of 1-5 mM does not protect the enzyme from the negative action of silver ions, but this inhibitory effect is almost completely removed by the corresponding concentrations of L-cysteine. The same noncompetitive character was inherent in the inhibition of alpha-galactosidase reaction by mercury ions and n-chlormercurybenzoat (Ki is 4.5 x 10(-6) and 1.8 x 10(-4), respectively). The importance of sulphydryl groups for the support of active comformation of alpha-galactosidase molecule was established on the basis of inhibition and kinetic analysis. It has been shown that the enzyme molecule does not contain the groups which include metal atoms. PMID:15554293

  12. Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus.

    PubMed

    Mattern, Derek J; Schoeler, Hanno; Weber, Jakob; Novohradská, Silvia; Kraibooj, Kaswara; Dahse, Hans-Martin; Hillmann, Falk; Valiante, Vito; Figge, Marc Thilo; Brakhage, Axel A

    2015-12-01

    The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. The genetic basis for the biosynthesis of a number of known metabolites has remained unknown. The gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. Here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene cluster in A. fumigatus. Genome mining identified tynC as an uncharacterized polyketide synthase with high similarity to known enzymes, whose products are structurally related to trypacidin including endocrocin and fumicycline. Gene deletion of tynC resulted in the complete absence of trypacidin production, which was fully restored when the mutant strain was complemented with the wild-type gene. When confronted with macrophages, the tynC deletion mutant conidia were more frequently phagocytosed than those of the parental wild-type strain. This was also found for phagocytic amoebae of the species Dictyostelium discoideum, which showed increased phagocytosis of ΔtynC conidia. Both macrophages and amoebae were also sensitive to trypacidin. Therefore, our results suggest that the conidium-bound trypacidin could have a protective function against phagocytes both in the environment and during the infection process. PMID:26278536

  13. The Volatome of Aspergillus fumigatus

    PubMed Central

    Calvo, A. M.; Latgé, J. P.

    2014-01-01

    Early detection of invasive aspergillosis is absolutely required for efficient therapy of this fungal infection. The identification of fungal volatiles in patient breath can be an alternative for the detection of Aspergillus fumigatus that still remains problematic. In this work, we investigated the production of volatile organic compounds (VOCs) by A. fumigatus in vitro, and we show that volatile production depends on the nutritional environment. A. fumigatus produces a multiplicity of VOCs, predominantly terpenes and related compounds. The production of sesquiterpenoid compounds was found to be strongly induced by increased iron concentrations and certain drugs, i.e., pravastatin. Terpenes that were always detectable in large amounts were α-pinene, camphene, and limonene, as well as sesquiterpenes, identified as α-bergamotene and β-trans-bergamotene. Other substance classes that were found to be present in the volatome, such as 1-octen-3-ol, 3-octanone, and pyrazines, were found only under specific growth conditions. Drugs that interfere with the terpene biosynthesis pathway influenced the composition of the fungal volatome, and most notably, a block of sesquiterpene biosynthesis by the bisphosphonate alendronate fundamentally changed the VOC composition. Using deletion mutants, we also show that a terpene cyclase and a putative kaurene synthase are essential for the synthesis of volatile terpenes by A. fumigatus. The present analysis of in vitro volatile production by A. fumigatus suggests that VOCs may be used in the diagnosis of infections caused by this fungus. PMID:24906414

  14. Asexual Sporulation in Aspergillus nidulans

    PubMed Central

    Adams, Thomas H.; Wieser, Jenny K.; Yu, Jae-Hyuk

    1998-01-01

    The formation of mitotically derived spores, called conidia, is a common reproductive mode in filamentous fungi, particularly among the large fungal class Ascomycetes. Asexual sporulation strategies are nearly as varied as fungal species; however, the formation of conidiophores, specialized multicellular reproductive structures, by the filamentous fungus Aspergillus nidulans has emerged as the leading model for understanding the mechanisms that control fungal sporulation. Initiation of A. nidulans conidipohore formation can occur either as a programmed event in the life cycle in response to intrinsic signals or to environmental stresses such as nutrient deprivation. In either case, a development-specific set of transcription factors is activated and these control the expression of each other as well as genes required for conidiophore morphogenesis. Recent progress has identified many of the earliest-acting genes needed for initiating conidiophore development and shown that there are at least two antagonistic signaling pathways that control this process. One pathway is modulated by a heterotrimeric G protein that when activated stimulates growth and represses both asexual and sexual sporulation as well as production of the toxic secondary metabolite, sterigmatocystin. The second pathway apparently requires an extracellular signal to induce sporulation-specific events and to direct the inactivation of the first pathway, removing developmental repression. A working model is presented in which the regulatory interactions between these two pathways during the fungal life cycle determine whether cells grow or develop. PMID:9529886

  15. Science Supporting Numeric Nutrient Criteria for Lakes and Their Watersheds: A Synopsis of Research Completed for the US Environmental Protection Agency

    EPA Science Inventory

    Nutrient pollution remains one of the most prevalent causes of water quality impairment in the United States. The U.S. Environmental Protection Agency’s (EPA) approach to addressing the challenge of managing nutrient pollution has included supporting development of numeric nutri...

  16. First case report of isolated aspergillus dacryoadenitis

    PubMed Central

    Acharya, Ishan; Basa, Divya; Kavitha, M

    2016-01-01

    We report a case of isolated Aspergillus dacryoadenitis. A 23-year-old male presented with dull ache, diffuse swelling in superolateral quadrant of the right orbit and proptosis for 4 months. Ocular examination showed conjunctival congestion, discharge in the fornix and palpable lacrimal gland (LG) mass. Routine hematological investigations followed by computed tomography scan of orbits were done. He did not respond to a course of systemic and topical antibiotics. Lateral orbitotomy with extended lid crease incision was performed with excision biopsy of LG. Abundant blackish material was found in the LG intraoperatively. The specimen was sent for histopathological examination (HPE). HPE report showed Aspergillus. Thorough ENT and systemic evaluation ruled out any other site with the fungus. To the best of our knowledge, this is the first case report of Aspergillus infection in LG. PMID:27488157

  17. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

    PubMed

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

    2016-07-01

    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. PMID:27170642

  18. A rare case of bilateral aspergillus endophthalmitis.

    PubMed

    Gupta, Saurabh; Loudill, Cameron; Tammara, Anita; Chow, Robert T

    2015-01-01

    Aspergillus endophthalmitis is a devastating inflammatory condition of the intraocular cavities that may result in irreparable loss of vision and rapid destruction of the eye. Almost all cases in the literature have shown an identified source causing aspergillus endophthalmitis as a result of direct extension of disease. We present a rare case of bilateral aspergillus endophthalmitis. A 72-year-old woman with a history of diabetes mellitus, congenital Hirschsprung disease, and recent culture-positive candida pyelonephritis with hydronephrosis status post-surgical stent placement presented with difficulty opening her eyes. She complained of decreased vision (20/200) with pain and redness in both eyes - right worse then left. Examination demonstrated multiple white fungal balls in both retinas consistent with bilateral fungal endophthalmitis. Bilateral vitreous taps for cultures and staining were performed. Patient was given intravitreal injections of amphotericin B, vancomycin, ceftazidime, and started on oral fluconazole. Patient was scheduled for vitrectomy to decrease organism burden and to remove loculated areas of infection that would not respond to systemic antifungal agents. Four weeks after initial presentation, the fungal cultures revealed mold growth consistent with aspergillus. Patient was subsequently started on voriconazole and fluconazole was discontinued due to poor efficacy against aspergillus. Further workup was conducted to evaluate for the source of infection and seeding. Transthoracic cardiogram was unremarkable for any vegetation or valvular abnormalities. MRI of the orbits and sinuses did not reveal any mass lesions or bony destruction. CT of the chest was unremarkable for infection. Aspergillus endophthalmitis may occur because of one of these several mechanisms: hematogenous dissemination, direct inoculation by trauma, and contamination during surgery. Our patient's cause of bilateral endophthalmitis was through an unknown iatrogenic seed

  19. A rare case of bilateral aspergillus endophthalmitis

    PubMed Central

    Gupta, Saurabh; Loudill, Cameron; Tammara, Anita; Chow, Robert T.

    2015-01-01

    Aspergillus endophthalmitis is a devastating inflammatory condition of the intraocular cavities that may result in irreparable loss of vision and rapid destruction of the eye. Almost all cases in the literature have shown an identified source causing aspergillus endophthalmitis as a result of direct extension of disease. We present a rare case of bilateral aspergillus endophthalmitis. A 72-year-old woman with a history of diabetes mellitus, congenital Hirschsprung disease, and recent culture-positive candida pyelonephritis with hydronephrosis status post-surgical stent placement presented with difficulty opening her eyes. She complained of decreased vision (20/200) with pain and redness in both eyes – right worse then left. Examination demonstrated multiple white fungal balls in both retinas consistent with bilateral fungal endophthalmitis. Bilateral vitreous taps for cultures and staining were performed. Patient was given intravitreal injections of amphotericin B, vancomycin, ceftazidime, and started on oral fluconazole. Patient was scheduled for vitrectomy to decrease organism burden and to remove loculated areas of infection that would not respond to systemic antifungal agents. Four weeks after initial presentation, the fungal cultures revealed mold growth consistent with aspergillus. Patient was subsequently started on voriconazole and fluconazole was discontinued due to poor efficacy against aspergillus. Further workup was conducted to evaluate for the source of infection and seeding. Transthoracic cardiogram was unremarkable for any vegetation or valvular abnormalities. MRI of the orbits and sinuses did not reveal any mass lesions or bony destruction. CT of the chest was unremarkable for infection. Aspergillus endophthalmitis may occur because of one of these several mechanisms: hematogenous dissemination, direct inoculation by trauma, and contamination during surgery. Our patient's cause of bilateral endophthalmitis was through an unknown iatrogenic seed

  20. Intranasal Immunization of Baculovirus Displayed Hemagglutinin Confers Complete Protection against Mouse Adapted Highly Pathogenic H7N7 Reassortant Influenza Virus

    PubMed Central

    Rajesh Kumar, Subaschandrabose; Syed Khader, Syed Musthaq; Kiener, Tanja K.; Szyporta, Milene; Kwang, Jimmy

    2013-01-01

    Background Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. Methodology/Principal Findings In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA). The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n.) or subcutaneously (s.c.) with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. Conclusion Our results indicated that protection from high pathogenic H7N7 (NL/219/03) virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections. PMID:23762234

  1. Aspergillus species: An emerging pathogen in onychomycosis among diabetics

    PubMed Central

    Wijesuriya, T. M.; Kottahachchi, J.; Gunasekara, T. D. C. P.; Bulugahapitiya, U.; Ranasinghe, K. N. P.; Neluka Fernando, S. S.; Weerasekara, M. M.

    2015-01-01

    Introduction: Approximately, 33% patients with diabetes are afflicted with onychomycosis. In the past, nondermatophyte molds have been regarded as opportunistic pathogens; recently, Aspergillus species are considered as emerging pathogens of toenail infections. In Sri Lanka, the prevalence of Aspergillus species in onychomycosis among diabetics is not well documented. Objective: To determine the proportion of Aspergillus onychomycosis, risk factors and knowledge among diabetics. Materials and Methods: This was descriptive cross-sectional study. Three hundred diabetic patients were included. Clinical examinations of patients’ toenails were performed by a clinical microbiologist. Laboratory identification was done, and pathogens were identified to the species level by morpho-physiological methods. All inferential statistics were tested at P < 0.05. Results: Among clinically suspected patients, 85% (255/300) were mycologically confirmed to have onychomycosis. Aspergillus species were most commonly isolated n = 180 (71%) followed by dermatophytes, yeasts, and other molds n = 75 (29%). Of the patients having Aspergillus onychomycosis, 149 (83%) were in the > age group. In men, Aspergillus onycomycosis was seen in 82%. Among patients who had Aspergillus nail infection, 114 (63%) had diabetes for a period of > years. Among patients who were engaged in agricultural activities, 77% were confirmed to have infected nails due to Aspergillus species. Conclusion: Aspergillus niger was the most common pathogen isolated from toenail infection. Aspergillus species should be considered as an important pathogen in toenail onychomycosis in diabetic patients. Risk factors associated with Aspergillus onychomycosis were age, gender, duration of diabetes, length of exposure to fungi, and occupation. PMID:26693433

  2. Enhanced diversity and aflatoxigenicity in interspecific hybrids of Aspergillus flavus and Aspergillus parasiticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus and A. parasiticus are two of the most important aflatoxin-producing species that contaminate agricultural commodities worldwide. Both species are heterothallic and undergo sexual reproduction in laboratory crosses. Here, we examine the possibility of interspecific matings betwe...

  3. In-silico analysis of Aspergillus niger beta-glucosidases

    NASA Astrophysics Data System (ADS)

    Yeo S., L.; Shazilah, K.; Suhaila, S.; Abu Bakar F., D.; Murad A. M., A.

    2014-09-01

    Genomic data mining was carried out and revealed a total of seventeen β-glucosidases in filamentous fungi Aspergillus niger. Two of them belonged to glycoside hydrolase family 1 (GH1) while the rest belonged to genes in family 3 (GH3). These proteins were then named according to the nomenclature as proposed by the International Union of Biochemistry (IUB), starting from the lowest pI and glycoside hydrolase family. Their properties were predicted using various bionformatic tools showing the presence of domains for signal peptide and active sites. Interestingly, one particular domain, PA14 (protective antigen) was present in four of the enzymes, predicted to be involved in carbohydrate binding. A phylogenetic tree grouped the two glycoside hydrolase families with GH1 and GH3 related organisms. This study showed that the various domains present in these β-glucosidases are postulated to be crucial for the survival of this fungus, as supported by other analysis.

  4. Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs.

    PubMed

    Greco, Mariana; Kemppainen, Minna; Pose, Graciela; Pardo, Alejandro

    2015-09-01

    Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds. PMID:26364643

  5. Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs

    PubMed Central

    Greco, Mariana; Kemppainen, Minna; Pose, Graciela; Pardo, Alejandro

    2015-01-01

    Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds. PMID:26364643

  6. Aspergillus flavus Genomics for Controlling Aflatoxin Contamination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The main objectives of the Aspergillus flavus genomics program are to identify genes and regulatory components involved in aflatoxin biosynthesis for solving aflatoxin contamination in agricultural crops. A. flavus Expressed Sequence Tags (EST), microarray and whole genome sequencing have been achi...

  7. Recombination and cryptic heterokaryosis in Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus is a pathogen of many agronomically important crops worldwide and can also cause human and animal diseases. A. flavus is the major producer of aflatoxins (AFs), which are carcinogenic secondary metabolites. In the United States, mycotoxins have been estimated to cause agricultur...

  8. Negative regulation and developmental competence in Aspergillus.

    PubMed

    Lee, Mi-Kyung; Kwon, Nak-Jung; Lee, Im-Soon; Jung, Seunho; Kim, Sun-Chang; Yu, Jae-Hyuk

    2016-01-01

    Asexual development (conidiation) in the filamentous fungus Aspergillus nidulans is governed by orchestrated gene expression. The three key negative regulators of conidiation SfgA, VosA, and NsdD act at different control point in the developmental genetic cascade. Here, we have revealed that NsdD is a key repressor affecting the quantity of asexual spores in Aspergillus. Moreover, nullifying both nsdD and vosA results in abundant formation of the development specific structure conidiophores even at 12 h of liquid culture, and near constitutive activation of conidiation, indicating that acquisition of developmental competence involves the removal of negative regulation exerted by both NsdD and VosA. NsdD's role in repressing conidiation is conserved in other aspergilli, as deleting nsdD causes enhanced and precocious activation of conidiation in Aspergillus fumigatus or Aspergillus flavus. In vivo NsdD-DNA interaction analyses identify three NsdD binding regions in the promoter of the essential activator of conidiation brlA, indicating a direct repressive role of NsdD in conidiation. Importantly, loss of flbC or flbD encoding upstream activators of brlA in the absence of nsdD results in delayed activation of brlA, suggesting distinct positive roles of FlbC and FlbD in conidiation. A genetic model depicting regulation of conidiation in A. nidulans is presented. PMID:27364479

  9. Genomics of peanut-Aspergillus flavus interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxin contamination caused by Aspergillus fungi is a great concern in peanut production worldwide. Pre-harvest Aspergillii infection and aflatoxin contamination are usually severe in peanuts that are grown under drought stressed conditions. Genomic research can provide new tools and resources to...

  10. Interaction between maize seed and Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus is an opportunistic fungal pathogen that colonizes maize seeds and contaminates them with aflatoxin. The fungus is localized in the endosperm and aleurone. To investigate the plant microbe interaction, we conducted histological and molecular studies to characterize the internal co...

  11. Evaluation of aflatoxin degradation by Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxins are highly toxic and hepatocarcinogenic compounds produced by Aspergillus flavus and A. parasiticus during infection of corn (maize), peanuts, cotton seed, and tree nuts (Figure 1). To minimize exposure to aflatoxins the U.S. Food and Drug Administration enforces a 20 ppb limit of aflatox...

  12. Negative regulation and developmental competence in Aspergillus

    PubMed Central

    Lee, Mi-Kyung; Kwon, Nak-Jung; Lee, Im-Soon; Jung, Seunho; Kim, Sun-Chang; Yu, Jae-Hyuk

    2016-01-01

    Asexual development (conidiation) in the filamentous fungus Aspergillus nidulans is governed by orchestrated gene expression. The three key negative regulators of conidiation SfgA, VosA, and NsdD act at different control point in the developmental genetic cascade. Here, we have revealed that NsdD is a key repressor affecting the quantity of asexual spores in Aspergillus. Moreover, nullifying both nsdD and vosA results in abundant formation of the development specific structure conidiophores even at 12 h of liquid culture, and near constitutive activation of conidiation, indicating that acquisition of developmental competence involves the removal of negative regulation exerted by both NsdD and VosA. NsdD’s role in repressing conidiation is conserved in other aspergilli, as deleting nsdD causes enhanced and precocious activation of conidiation in Aspergillus fumigatus or Aspergillus flavus. In vivo NsdD-DNA interaction analyses identify three NsdD binding regions in the promoter of the essential activator of conidiation brlA, indicating a direct repressive role of NsdD in conidiation. Importantly, loss of flbC or flbD encoding upstream activators of brlA in the absence of nsdD results in delayed activation of brlA, suggesting distinct positive roles of FlbC and FlbD in conidiation. A genetic model depicting regulation of conidiation in A. nidulans is presented. PMID:27364479

  13. New species in Aspergillus section Terrei

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus section Terrei is reviewed and revised using information from DNA sequences, extrolite examination, and phenotypic assessment in an integrated analysis. The taxonomic status of six species from the section is modified either by describing new species or by providing new names for previou...

  14. Genomic analysis of aspergillus flavus pathogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus and Fusarium verticillioides colonize developing maize seeds and contaminate them with mycotoxins. Maize genotypes differ in resistance to these fungi, but incorporation of adequate resistance into desirable hybrids has been challenging.Little is known about pathogenesis of seeds...

  15. Draft Genome Sequences of Fungus Aspergillus calidoustus.

    PubMed

    Horn, Fabian; Linde, Jörg; Mattern, Derek J; Walther, Grit; Guthke, Reinhard; Scherlach, Kirstin; Martin, Karin; Brakhage, Axel A; Petzke, Lutz; Valiante, Vito

    2016-01-01

    Here, we report the draft genome sequence of Aspergillus calidoustus (strain SF006504). The functional annotation of A. calidoustus predicts a relatively large number of secondary metabolite gene clusters. The presented genome sequence builds the basis for further genome mining. PMID:26966204

  16. ASPERGILLUS BOMBYCIS GENOTYPES (RFLP) FROM SILKWORM CULTIVATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eighteen isolates of Aspergillus bombycis from samples of dust, insect frass, and soil collected from 8 silkworm rearing facilities in Japan, as well as single silkworm rearing facilities in Indonesia and Malaysia, were subjected to DNA fingerprinting. PstI digests of total genomic DNA from each is...

  17. The sexual state of Aspergillus parasiticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The sexual state of Aspergillus parasiticus, a potent aflatoxin-producing fungus within section Flavi, is described. The production of nonostiolate ascocarps surrounded by a separate peridium within the stroma places the teleomorph in the genus Petromyces. Petromyces parasiticus differs from P. a...

  18. Draft Genome Sequences of Fungus Aspergillus calidoustus

    PubMed Central

    Horn, Fabian; Linde, Jörg; Mattern, Derek J.; Walther, Grit; Guthke, Reinhard; Scherlach, Kirstin; Martin, Karin; Brakhage, Axel A.; Petzke, Lutz

    2016-01-01

    Here, we report the draft genome sequence of Aspergillus calidoustus (strain SF006504). The functional annotation of A. calidoustus predicts a relatively large number of secondary metabolite gene clusters. The presented genome sequence builds the basis for further genome mining. PMID:26966204

  19. Cyclopiazonic acid biosynthesis by Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclopiazonic acid (CPA) is an indole-tetramic acid mycotoxin produced by some strains of Aspergillus flavus. Characterization of the CPA biosynthesis gene cluster confirmed that formation of CPA is via a three-enzyme pathway. This review examines the structure and organization of the CPA genes, elu...

  20. Biotransformation of Stypotriol triacetate by Aspergillus niger

    NASA Astrophysics Data System (ADS)

    Areche, Carlos; Vaca, Inmaculada; Labbe, Pamela; Soto-Delgado, Jorge; Astudillo, Luis; Silva, Mario; Rovirosa, Juana; San-Martin, Aurelio

    2011-07-01

    Biological transformation of the meroditerpenoid, stypotriol triacetate ( 1) by the fungi Aspergillus niger, Cunninghamella elegans, Gibberella fujikuroi and Mucor plumbeus was studied. The incubation of 1 with A. niger yielded the new compound 6',14-diacetoxy-stypol-4,5-dione ( 2) whose structure was established by 1H, 13C and 2D NMR and supported by DFT/GIAO.

  1. Phylogeny and subgeneric taxonomy of Aspergillus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The phylogeny of the genus Aspergillus and its teleomorphs is discussed based on multilocus sequence data. DNA sequence analysis was used to formulate a nucleotide sequence framework of the genus and to analyze character changes in relationship to the phylogeny hypothesized from the DNA sequence an...

  2. Biological control of AFB1-producing Aspergillus section Flavi strains isolated from brewer's grains, alternative feed intended for swine production in Argentina.

    PubMed

    Asurmendi, Paula; García, María J; Ruíz, Francisco; Dalcero, Ana; Pascual, Liliana; Barberis, Lucila

    2016-07-01

    The aim of the present study was to investigate the inhibitory activity of lactic acid bacteria (LAB) isolated from brewer's grains on Aspergillus section Flavi growth and aflatoxin B1 production. The Aspergillus strains tested were inhibited by all the LAB strains assayed. The isolates Lactobacillus brevis B20, P. pentosaceus B86, Lactococcus lactis subsp. lactis B87, L. brevis B131, and Lactobacillus sp. B144 completely suppressed the fungal growth and reduced aflatoxin B1 production. In conclusion, LAB isolated from brewer's grains show a high inhibitory activity on fungal growth and aflatoxin biosynthesis by Aspergillus flavus and Aspergillus parasiticus. Further studies must be conducted to evaluate the success of in vitro assays under food environment conditions and to elucidate the antifungal mechanism of these strains. PMID:27070819

  3. Impact of Aspergillus oryzae genomics on industrial production of metabolites.

    PubMed

    Abe, Keietsu; Gomi, Katusya; Hasegawa, Fumihiko; Machida, Masayuki

    2006-09-01

    Aspergillus oryzae is used extensively for the production of the traditional Japanese fermented foods sake (rice wine), shoyu (soy sauce), and miso (soybean paste). In recent years, recombinant DNA technology has been used to enhance industrial enzyme production by A. oryzae. Recently completed genomic studies using expressed sequence tag (EST) analyses and whole-genome sequencing are quickly expanding the industrial potential of the fungus in biotechnology. Genes that have been newly discovered through genome research can be used for the production of novel valuable enzymes and chemicals, and are important for designing new industrial processes. This article describes recent progress of A . oryzae genomics and its impact on industrial production of enzymes, metabolites, and bioprocesses. PMID:16944282

  4. Effect of essential oils on Aspergillus spore germination, growth and mycotoxin production: a potential source of botanical food preservative

    PubMed Central

    Gemeda, Negero; Woldeamanuel, Yimtubezinash; Asrat, Daniel; Debella, Asfaw

    2014-01-01

    Objective To investigate effect of essential oils on Aspergillus spore germination, growth and mycotoxin production. Method In vitro antifungal and antiaflatoxigenic activity of essential oils was carried out using poisoned food techniques, spore germination assay, agar dilution assay, and aflatoxin arresting assay on toxigenic strains of Aspergillus species. Results Cymbopogon martinii, Foeniculum vulgare and Trachyspermum ammi (T. ammi) essential oils were tested against toxicogenic isolates of Aspergillus species. T. ammi oil showed highest antifungal activity. Absolute mycelial inhibition was recorded at 1 µl/mL by essential oils of T. ammi. The oil also showed, complete inhibition of spore germination at a concentration of 2 µl/mL. In addition, T. ammi oil showed significant antiaflatoxigenic potency by totally inhibiting aflatoxin production from Aspergillus niger and Aspergillus flavus at 0.5 and 0.75 µl/mL, respectively. Cymbopogon martinii, Foeniculum vulgare and T. ammi oils as antifungal were found superior over synthetic preservative. Moreover, a concentration of 5 336.297 µl/kg body weight was recorded for LC50 on mice indicating the low mammalian toxicity and strengthening its traditional reputations. Conclusions In conclusion, the essential oils from T. ammi can be a potential source of safe natural food preservative for food commodities contamination by storage fungi. PMID:25183114

  5. Human polymorphonuclear leukocytes inhibit Aspergillus fumigatus conidial growth by lactoferrin-mediated iron depletion.

    PubMed

    Zarember, Kol A; Sugui, Janyce A; Chang, Yun C; Kwon-Chung, Kyung J; Gallin, John I

    2007-05-15

    Aspergillus fumigatus, a common mold, rarely infects humans, except during prolonged neutropenia or in cases of chronic granulomatous disease (CGD), a primary immunodeficiency caused by mutations in the NADPH oxidase that normally produces fungicidal reactive oxygen species. Filamentous hyphae of Aspergillus are killed by normal, but not CGD polymorphonuclear leukocytes (PMN); however, the few studies on PMN-mediated host defenses against infectious conidia (spores) of this organism have yielded conflicting results, some showing that PMN do not inhibit conidial growth, with others showing that they do, most likely using reactive oxygen species. Given that CGD patients are exposed daily to hundreds of viable A. fumigatus conidia, yet considerable numbers of them survive years without infection, we reasoned that PMN use ROS-independent mechanisms to combat Aspergillus. We show that human PMN from both normal controls and CGD patients are equipotent at arresting the growth of Aspergillus conidia in vitro, indicating the presence of a reactive oxygen species-independent factor(s). Cell-free supernatants of degranulated normal and CGD neutrophils both suppressed fungal growth and were found to be rich in lactoferrin, an abundant PMN secondary granule protein. Purified iron-poor lactoferrin at concentrations occurring in PMN supernatants (and reported in human mucosal secretions in vivo) decreased fungal growth, whereas saturation of lactoferrin or PMN supernatants with iron, or testing in the presence of excess iron in the form of ferritin, completely abolished activity against conidia. These results demonstrate that PMN lactoferrin sequestration of iron is important for host defense against Aspergillus. PMID:17475866

  6. 40 CFR 72.61 - Completeness.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Completeness. 72.61 Section 72.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Federal Acid Rain Permit Issuance Procedures § 72.61 Completeness. (a) Determination of Completeness. The Administrator will...

  7. New taxa in Aspergillus section Usti

    PubMed Central

    Samson, R.A.; Varga, J.; Meijer, M.; Frisvad, J.C.

    2011-01-01

    Based on phylogenetic analysis of sequence data, Aspergillus section Usti includes 21 species, inclucing two teleomorphic species Aspergillus heterothallicus (= Emericella heterothallica) and Fennellia monodii. Aspergillus germanicus sp. nov. was isolated from indoor air in Germany. This species has identical ITS sequences with A. insuetus CBS 119.27, but is clearly distinct from that species based on β-tubulin and calmodulin sequence data. This species is unable to grow at 37 °C, similarly to A. keveii and A. insuetus. Aspergillus carlsbadensis sp. nov. was isolated from the Carlsbad Caverns National Park in New Mexico. This taxon is related to, but distinct from a clade including A. calidoustus, A. pseudodeflectus, A. insuetus and A. keveii on all trees. This species is also unable to grow at 37 °C, and acid production was not observed on CREA. Aspergillus californicus sp. nov. is proposed for an isolate from chamise chaparral (Adenostoma fasciculatum) in California. It is related to a clade including A. subsessilis and A. kassunensis on all trees. This species grew well at 37 °C, and acid production was not observed on CREA. The strain CBS 504.65 from soil in Turkey showed to be clearly distinct from the A. deflectus ex-type strain, indicating that this isolate represents a distinct species in this section. We propose the name A. turkensis sp. nov. for this taxon. This species grew, although rather restrictedly at 37 °C, and acid production was not observed on CREA. Isolates from stored maize, South Africa, as a culture contaminant of Bipolaris sorokiniana from indoor air in Finland proved to be related to, but different from A. ustus and A. puniceus. The taxon is proposed as the new species A. pseudoustus. Although supported only by low bootstrap values, F. monodii was found to belong to section Usti based on phylogenetic analysis of either loci BLAST searches to the GenBank database also resulted in closest hits from section Usti. This species obviously

  8. Complete diphallia.

    PubMed

    Acimi, Smail

    2008-01-01

    A case of complete diphallia in a 4-month-old boy is reported. This is the second case to be published from this institution. The embryogenesis and associated anomalies of diphallia are discussed, together with a proposal for a classification based on anatomical, functional and therapeutic aspects of the malformation. PMID:19230173

  9. Recoding structural glycoprotein E2 in classical swine fever virus (CSFV) produces complete virus attenuation in swine and protects infected animals against disease.

    PubMed

    Velazquez-Salinas, Lauro; Risatti, Guillermo R; Holinka, Lauren G; O'Donnell, Vivian; Carlson, Jolene; Alfano, Marialexia; Rodriguez, Luis L; Carrillo, Consuelo; Gladue, Douglas P; Borca, Manuel V

    2016-07-01

    Controlling classical swine fever (CSF) mainly involves vaccination with live attenuated vaccines (LAV). Experimental CSFV LAVs has been lately developed through reverse genetics using several different approaches. Here we present that codon de-optimization in the major CSFV structural glycoprotein E2 coding region, causes virus attenuation in swine. Four different mutated constructs (pCSFm1-pCSFm4) were designed using various mutational approaches based on the genetic background of the highly virulent strain Brescia (BICv). Three of these constructs produced infectious viruses (CSFm2v, CSFm3v, and CSFm4v). Animals infected with CSFm2v presented a reduced and extended viremia but did not display any CSF-related clinical signs. Animals that were infected with CSFm2v were protected against challenge with virulent parental BICv. This is the first report describing the development of an attenuated CSFV experimental vaccine by codon usage de-optimization, and one of the few examples of virus attenuation using this methodology that is assessed in a natural host. PMID:27110709

  10. Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae

    PubMed Central

    2014-01-01

    Background The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome. Results Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase. Conclusion In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus. PMID:24961398

  11. Aspergillus bertholletius sp. nov. from Brazil nuts.

    PubMed

    Taniwaki, Marta H; Pitt, John I; Iamanaka, Beatriz T; Sartori, Daniele; Copetti, Marina V; Balajee, Arun; Fungaro, Maria Helena P; Frisvad, Jens C

    2012-01-01

    During a study on the mycobiota of brazil nuts (Bertholletia excelsa) in Brazil, a new Aspergillus species, A. bertholletius, was found, and is described here. A polyphasic approach was applied using morphological characters, extrolite data as well as partial β-tubulin, calmodulin and ITS sequences to characterize this taxon. A. bertholletius is represented by nineteen isolates from samples of brazil nuts at various stages of production and soil close to Bertholletia excelsa trees. The following extrolites were produced by this species: aflavinin, cyclopiazonic acid, kojic acid, tenuazonic acid and ustilaginoidin C. Phylogenetic analysis using partial β-tubulin and camodulin gene sequences showed that A. bertholletius represents a new phylogenetic clade in Aspergillus section Flavi. The type strain of A. bertholletius is CCT 7615 ( = ITAL 270/06 = IBT 29228). PMID:22952594

  12. Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis

    PubMed Central

    Dagenais, Taylor R. T.; Keller, Nancy P.

    2009-01-01

    Summary: Aspergillus species are globally ubiquitous saprophytes found in a variety of ecological niches. Almost 200 species of aspergilli have been identified, less than 20 of which are known to cause human disease. Among them, Aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis (IA) in the immunocompromised patient population. IA is a devastating illness, with mortality rates in some patient groups reaching as high as 90%. Studies identifying and assessing the roles of specific factors of A. fumigatus that contribute to the pathogenesis of IA have traditionally focused on single-gene deletion and mutant characterization. In combination with recent large-scale approaches analyzing global fungal responses to distinct environmental or host conditions, these studies have identified many factors that contribute to the overall pathogenic potential of A. fumigatus. Here, we provide an overview of the significant findings regarding A. fumigatus pathogenesis as it pertains to invasive disease. PMID:19597008

  13. Aspergillus bertholletius sp. nov. from Brazil Nuts

    PubMed Central

    Taniwaki, Marta H.; Pitt, John I.; Iamanaka, Beatriz T.; Sartori, Daniele; Copetti, Marina V.; Balajee, Arun; Fungaro, Maria Helena P.; Frisvad, Jens C.

    2012-01-01

    During a study on the mycobiota of brazil nuts (Bertholletia excelsa) in Brazil, a new Aspergillus species, A. bertholletius, was found, and is described here. A polyphasic approach was applied using morphological characters, extrolite data as well as partial β-tubulin, calmodulin and ITS sequences to characterize this taxon. A. bertholletius is represented by nineteen isolates from samples of brazil nuts at various stages of production and soil close to Bertholletia excelsa trees. The following extrolites were produced by this species: aflavinin, cyclopiazonic acid, kojic acid, tenuazonic acid and ustilaginoidin C. Phylogenetic analysis using partial β-tubulin and camodulin gene sequences showed that A. bertholletius represents a new phylogenetic clade in Aspergillus section Flavi. The type strain of A. bertholletius is CCT 7615 ( = ITAL 270/06 = IBT 29228). PMID:22952594

  14. Complete Protection of Mice against Lethal Murine Cytomegalovirus Challenge by Immunization with DNA Vaccines Encoding Envelope Glycoprotein Complex III Antigens gH, gL and gO

    PubMed Central

    Wang, Huadong; Huang, Chaoyang; Dong, Jinrong; Yao, Yanfeng; Xie, Zhenyuan; Liu, Xueying; Zhang, Wenjie; Fang, Fang; Chen, Ze

    2015-01-01

    Human cytomegalovirus infects the majority of humanity which may lead to severe morbidity and mortality in newborns and immunocompromised adults. Humoral and cellular immunity are critical for controlling CMV infection. HCMV envelope glycoprotein complexes (gC I, II, III) represent major antigenic targets of antiviral immune responses. The gCIII complex is comprised of three glycoproteins, gH, gL, and gO. In the present study, DNA vaccines expressing the murine cytomegalovirus homologs of the gH, gL, and gO proteins were evaluated for protection against lethal MCMV infection in the mouse model. The results demonstrated that gH, gL, or gO single gene immunization could not yet offer good protection, whereas co-vaccination strategy apparently showed effects superior to separate immunization. Twice immunization with gH/gL/gO pDNAs could provide mice complete protection against lethal salivary gland-derived MCMV (SG-MCMV) challenge, while thrice immunization with pgH/pgL, pgH/pgO or pgL/pgO could not provide full protection. Co-vaccination with gH, gL and gO pDNAs elicited robust neutralizing antibody and cellular immune responses. Moreover, full protection was also achieved by simply passive immunization with anti-gH/gL/gO sera. These data demonstrated that gCIII complex antigens had fine immunogenicity and might be a promising candidate for the development of HCMV vaccines. PMID:25803721

  15. Expression of feruloyl esterase A from Aspergillus terreus and its application in biomass degradation.

    PubMed

    Zhang, Shuai-Bing; Wang, Le; Liu, Yan; Zhai, Huan-Chen; Cai, Jing-Ping; Hu, Yuan-Sen

    2015-11-01

    Feruloyl esterases (FAEs) are key enzymes involved in the complete biodegradation of lignocelluloses, which could hydrolyze the ester bonds between hemicellulose and lignin. The coding sequence of a feruloyl esterase A (AtFaeA) was cloned from Aspergillus terreus and the recombinant AtFaeA was constitutively expressed in Pichia pastoris. The SDS-PAGE analysis of purified AtFaeA showed two protein bands owing to the different extent of glycosylation, and the recombinant AtFaeA had an optimum temperature of 50°C and an optimum pH of 5.0. The substrate utilization and primary sequence identity of AtFaeA demonstrated that it is a type-A feruloyl esterase. The hydrolysis of corn stalk and corncob by xylanase from Aspergillus niger could be significantly improved in concert with recombinant AfFaeA. PMID:26282562

  16. 4-Ethylphenol metabolism by Aspergillus fumigatus

    SciTech Connect

    Jones, K.H.; Trudgill, P.W.; Hopper, D.J.

    1994-06-01

    Many industrial pollutants are phenolic, and the degradation these compounds is important in the carbon cycle. Aspergillus fumigatus ATCC 28282 can grow on p-cresol. However 4-Ethylphenol, the higher homolog of p-cresol, presents different possibilities for putative metabolic pathways. This study shows that A. fumigatus is able to grow and 4-ethylphenol and the pathway is described. 17 refs., 4 figs., 2 tabs.

  17. Western Analysis of Histone Modifications (Aspergillus nidulans)

    PubMed Central

    Soukup, Alexandra; Keller, Nancy P.

    2016-01-01

    Western blotting allows for the specific detection of proteins and/or modifications of proteins by an antibody of interest. This protocol utilizes a crude nuclei extraction protocol for Aspergillus nidulans to enrich for histones and other nuclear proteins prior to gel electrophoresis. Post translational modifications of histones may then be easily detected. After electrophoresis, the selected antibodies are used to detect and quantify levels of the modifications of interest.

  18. Comparative Reannotation of 21 Aspergillus Genomes

    SciTech Connect

    Salamov, Asaf; Riley, Robert; Kuo, Alan; Grigoriev, Igor

    2013-03-08

    We used comparative gene modeling to reannotate 21 Aspergillus genomes. Initial automatic annotation of individual genomes may contain some errors of different nature, e.g. missing genes, incorrect exon-intron structures, 'chimeras', which fuse 2 or more real genes or alternatively splitting some real genes into 2 or more models. The main premise behind the comparative modeling approach is that for closely related genomes most orthologous families have the same conserved gene structure. The algorithm maps all gene models predicted in each individual Aspergillus genome to the other genomes and, for each locus, selects from potentially many competing models, the one which most closely resembles the orthologous genes from other genomes. This procedure is iterated until no further change in gene models is observed. For Aspergillus genomes we predicted in total 4503 new gene models ( ~;;2percent per genome), supported by comparative analysis, additionally correcting ~;;18percent of old gene models. This resulted in a total of 4065 more genes with annotated PFAM domains (~;;3percent increase per genome). Analysis of a few genomes with EST/transcriptomics data shows that the new annotation sets also have a higher number of EST-supported splice sites at exon-intron boundaries.

  19. Complete prewetting

    NASA Astrophysics Data System (ADS)

    Yatsyshin, P.; Parry, A. O.; Kalliadasis, S.

    2016-07-01

    We study continuous interfacial transitions, analagous to two-dimensional complete wetting, associated with the first-order prewetting line, which can occur on steps, patterned walls, grooves and wedges, and which are sensitive to both the range of the intermolecular forces and interfacial fluctuation effects. These transitions compete with wetting, filling and condensation producing very rich phase diagrams even for relatively simple prototypical geometries. Using microscopic classical density functional theory to model systems with realistic Lennard-Jones fluid–fluid and fluid–substrate intermolecular potentials, we compute mean-field fluid density profiles, adsorption isotherms and phase diagrams for a variety of confining geometries.

  20. Antibiotic Extraction as a Recent Biocontrol Method for Aspergillus Niger andAspergillus Flavus Fungi in Ancient Egyptian mural paintings

    NASA Astrophysics Data System (ADS)

    Hemdan, R.; et al.

    Biodeterioration of mural paintings by Aspergillus niger and Aspergillus flavus Fungi has been proved in different mural paintings in Egypt nowadays. Several researches have studied the effect of fungi on mural paintings, the mechanism of interaction and methods of control. But none of these researches gives us the solution without causing a side effect. In this paper, for the first time, a recent treatment by antibiotic "6 penthyl α pyrone phenol" was applied as a successful technique for elimination of Aspergillus niger and Aspergillus flavus. On the other hand, it is favorable for cleaning Surfaces of Murals executed by tembera technique from the fungi metabolism which caused a black pigments on surfaces.

  1. Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge.

    PubMed

    Sholukh, Anton M; Watkins, Jennifer D; Vyas, Hemant K; Gupta, Sandeep; Lakhashe, Samir K; Thorat, Swati; Zhou, Mingkui; Hemashettar, Girish; Bachler, Barbara C; Forthal, Donald N; Villinger, Francois; Sattentau, Quentin J; Weiss, Robin A; Agatic, Gloria; Corti, Davide; Lanzavecchia, Antonio; Heeney, Jonathan L; Ruprecht, Ruth M

    2015-04-21

    Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the combination of the two neutralized the challenge virus equally well in vitro. All RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given HGN194 IgG1+dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL-p challenge. These data imply that combining suboptimal defenses at the mucosal and systemic levels can completely prevent virus acquisition. Consequently, active vaccination should focus on defense-in-depth, a strategy that seeks to build up defensive fall-back positions well behind the fortified frontline. PMID:25769884

  2. Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: Complete protection of rhesus monkeys from mucosal SHIV challenge

    PubMed Central

    Sholukh, Anton M.; Watkins, Jennifer D.; Vyas, Hemant K.; Gupta, Sandeep; Lakhashe, Samir K.; Thorat, Swati; Zhou, Mingkui; Hemashettar, Girish; Bachler, Barbara C.; Forthal, Donald N.; Villinger, Francois; Sattentau, Quentin J.; Weiss, Robin A.; Agatic, Gloria; Corti, Davide; Lanzavecchia, Antonio; Heeney, Jonathan L.; Ruprecht, Ruth M.

    2015-01-01

    Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the combination of the two neutralized the challenge virus equally well in vitro. All RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given HGN194 IgG1 + dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL-p challenge. These data imply that combining suboptimal defenses at the mucosal and systemic levels can completely prevent virus acquisition. Consequently, active vaccination should focus on defense-in-depth, a strategy that seeks to build up defensive fall-back positions well behind the fortified frontline. PMID:25769884

  3. Ecology, development and gene regulation in Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus is one of the most widely known species of Aspergillus. It was described as a species in 1809 and first reported as a plant pathogen in 1920. More recently, A. flavus has emerged as an important opportunistic pathogen and is now rec¬ognized as the second leading cause of aspergill...

  4. Genomic Islands in Pathogenic Filamentous Fungus Aspergillus fumigatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present the genome sequences of a new clinical isolate, CEA10, of an important human pathogen, Aspergillus fumigatus, and two closely related, but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of CEA10 with the recently sequen...

  5. Phylogeny, identification and nomenclature of the genus Aspergillus

    PubMed Central

    Samson, R.A.; Visagie, C.M.; Houbraken, J.; Hong, S.-B.; Hubka, V.; Klaassen, C.H.W.; Perrone, G.; Seifert, K.A.; Susca, A.; Tanney, J.B.; Varga, J.; Kocsubé, S.; Szigeti, G.; Yaguchi, T.; Frisvad, J.C.

    2014-01-01

    Aspergillus comprises a diverse group of species based on morphological, physiological and phylogenetic characters, which significantly impact biotechnology, food production, indoor environments and human health. Aspergillus was traditionally associated with nine teleomorph genera, but phylogenetic data suggest that together with genera such as Polypaecilum, Phialosimplex, Dichotomomyces and Cristaspora, Aspergillus forms a monophyletic clade closely related to Penicillium. Changes in the International Code of Nomenclature for algae, fungi and plants resulted in the move to one name per species, meaning that a decision had to be made whether to keep Aspergillus as one big genus or to split it into several smaller genera. The International Commission of Penicillium and Aspergillus decided to keep Aspergillus instead of using smaller genera. In this paper, we present the arguments for this decision. We introduce new combinations for accepted species presently lacking an Aspergillus name and provide an updated accepted species list for the genus, now containing 339 species. To add to the scientific value of the list, we include information about living ex-type culture collection numbers and GenBank accession numbers for available representative ITS, calmodulin, β-tubulin and RPB2 sequences. In addition, we recommend a standard working technique for Aspergillus and propose calmodulin as a secondary identification marker. PMID:25492982

  6. Sexual reproduction in Aspergillus tubingensis from section Nigri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A sclerotium-forming member of Aspergillus section Nigri was sampled from a population in a single field in North Carolina, USA, and identified as A. tubingensis based on genealogical concordance analysis. Aspergillus tubingensis was shown to be heterothallic, with individual strains containing ei...

  7. Phylogeny, identification and nomenclature of the genus Aspergillus.

    PubMed

    Samson, R A; Visagie, C M; Houbraken, J; Hong, S-B; Hubka, V; Klaassen, C H W; Perrone, G; Seifert, K A; Susca, A; Tanney, J B; Varga, J; Kocsubé, S; Szigeti, G; Yaguchi, T; Frisvad, J C

    2014-06-01

    Aspergillus comprises a diverse group of species based on morphological, physiological and phylogenetic characters, which significantly impact biotechnology, food production, indoor environments and human health. Aspergillus was traditionally associated with nine teleomorph genera, but phylogenetic data suggest that together with genera such as Polypaecilum, Phialosimplex, Dichotomomyces and Cristaspora, Aspergillus forms a monophyletic clade closely related to Penicillium. Changes in the International Code of Nomenclature for algae, fungi and plants resulted in the move to one name per species, meaning that a decision had to be made whether to keep Aspergillus as one big genus or to split it into several smaller genera. The International Commission of Penicillium and Aspergillus decided to keep Aspergillus instead of using smaller genera. In this paper, we present the arguments for this decision. We introduce new combinations for accepted species presently lacking an Aspergillus name and provide an updated accepted species list for the genus, now containing 339 species. To add to the scientific value of the list, we include information about living ex-type culture collection numbers and GenBank accession numbers for available representative ITS, calmodulin, β-tubulin and RPB2 sequences. In addition, we recommend a standard working technique for Aspergillus and propose calmodulin as a secondary identification marker. PMID:25492982

  8. Biodiversity of Aspergillus Species in Some Important Agricultural Products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Aspergillus is one of the most important filamentous fungal genera. Aspergillus species are used in the fermentation industry, but they are also responsible of various plant and food secondary rot, with the consequence of possible accumulation of mycotoxins. The aflatoxin-producing A. fl...

  9. Clonality and sex impact aflatoxigenicity in Aspergillus populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Species in Aspergillus section Flavi commonly infect agricultural staples such as corn, peanuts, cottonseed, and tree nuts and produce an array of mycotoxins, the most potent of which are aflatoxins. Aspergillus flavus is the dominant aflatoxin-producing species in the majority of crops. Populatio...

  10. The current status of species recognition and identification in Aspergillus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Aspergillus is a large economically important genus of fungi. In agriculture, some of the 250 species in this genus cause disease in plants and animals and some also produce poisons (mycotoxins) in foods and feeds. Aspergillus is a major killer of immunosuppressed people, such as diabeti...

  11. Fatal coinfection with Legionella pneumophila serogroup 8 and Aspergillus fumigatus.

    PubMed

    Guillouzouic, Aurélie; Bemer, Pascale; Gay-Andrieu, Françoise; Bretonnière, Cédric; Lepelletier, Didier; Mahé, Pierre-Joachim; Villers, Daniel; Jarraud, Sophie; Reynaud, Alain; Corvec, Stéphane

    2008-02-01

    Legionella pneumophila is an important cause of community-acquired and nosocomial pneumonia. We report on a patient who simultaneously developed L. pneumophila serogroup 8 pneumonia and Aspergillus fumigatus lung abscesses. Despite appropriate treatments, Aspergillus disease progressed with metastasis. Coinfections caused by L. pneumophila and A. fumigatus remain exceptional. In apparently immunocompetent patients, corticosteroid therapy is a key risk factor for aspergillosis. PMID:17945454

  12. What can Aspergillus flavus genome offer for mycotoxin research?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genomic study of filamentous fungi has made significant advances in recent years, and the genomes of several species in the genus Aspergillus have been sequenced, including Aspergillus flavus. This ubiquitous mold is present as a saprobe in a wide range of agricultural and natural habits, and c...

  13. A first glance into the genome sequence of Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxins, produced by Aspergillus flavus and A. parasiticus, are toxic and carcinogenic metabolites. They contaminate agricultural crops before harvest and post harvest grains during storage. In order to reduce and eliminate aflatoxin contamination of food and feed, Aspergillus flavus genomics p...

  14. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

    PubMed

    van der Linden, J W M; Arendrup, M C; Warris, A; Lagrou, K; Pelloux, H; Hauser, P M; Chryssanthou, E; Mellado, E; Kidd, S E; Tortorano, A M; Dannaoui, E; Gaustad, P; Baddley, J W; Uekötter, A; Lass-Flörl, C; Klimko, N; Moore, C B; Denning, D W; Pasqualotto, A C; Kibbler, C; Arikan-Akdagli, S; Andes, D; Meletiadis, J; Naumiuk, L; Nucci, M; Melchers, W J G; Verweij, P E

    2015-06-01

    To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. PMID:25988348

  15. WHOLE GENOME COMPARISON OF ASPERGILLUS FLAVUS AND A. ORYZAE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus is a plant and animal pathogen that also produces the potent carcinogen aflatoxin. Aspergillus oryzae is a closely related species that has been used for centuries in the food fermentation industry and is generally regarded as safe (GRAS). Whole genome sequences for these two fu...

  16. Control of Aspergillus flavus in maize with plant essential oils and their components.

    PubMed

    Montes-Belmont, R; Carvajal, M

    1998-05-01

    The effects of 11 plant essential oils for maize kernel protection against Aspergillus flavus were studied. Tests were conducted to determine optimal levels of dosages for maize protection, effects of combinations of essential oils, and residual effects and toxicity of essential oils to maize plants. Principal constituents of eight essential oils were tested for ability to protect maize kernels. Essential oils of Cinnamomum zeylanicum (cinnamon), Mentha piperita (peppermint), Ocimum basilicum (basil), Origanum vulgare (origanum), Teloxys ambrosioides (the flavoring herb epazote), Syzygium aromaticum (clove), and Thymus vulgaris (thyme) caused a total inhibition of fungal development on maize kernels. Thymol and o-methoxycinnamaldehyde significantly reduced maize grain contamination. The optimal dosage for protection of maize varied from 3 to 8%. Combinations of C. zeylanicum with the remaining oils gave efficient control. A residual effect of C. zeylanicum was detected after 4 weeks of kernel treatment. No phytotoxic effect on germination and corn growth was detected with any of these oils. PMID:9709236

  17. Aspergillus pragensis sp. nov. discovered during molecular reidentification of clinical isolates belonging to Aspergillus section Candidi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The identity of nine clinical isolates from Czech patients presumably belonging to Aspergillus section Candidi based on morphology of colonies was revised using sequences of ß-tubulin, calmodulin, and internal transcribed spacer (ITS) rDNA. The set of isolates included six isolates from suspected (n...

  18. Aflatoxin Biosynthesis and Sclerotial Development in Aspergillus flavus and Aspergillus parasiticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxins are a family of fungal secondary metabolites. They are produced by species in the genus Aspergillus. Within the last decade, significant advances have been made in understanding the biochemistry, genetics, and gene regulation of aflatoxin biosynthesis. Many scientists have used aflatox...

  19. Aspergillus tanneri sp. nov, a new pathogenic Aspergillus that causes invasive disease refractory to antifungal therapy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is the first report documenting fatal invasive aspergillosis caused by a new pathogenic Aspergillus species that is inherently resistant to antifungal drugs. Phenotypic characteristics of A. tanneri combined with the molecular approach enabled diagnosis of this new pathogen. This study undersco...

  20. The population genomics of mycotoxin diversity in Aspergillus flavus and Aspergillus parasiticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycotoxins, and especially the aflatoxins, are an enormous problem in agriculture, with aflatoxin B1 being the most carcinogenic known natural compound. The worldwide costs associated with aflatoxin monitoring and crop losses are in the hundreds of millions of dollars. Aspergillus flavus and A. par...

  1. ADOPTING SELECTED HYDROGEN BONDING AND IONIC INTERACTIONS FROM ASPERGILLUS FUMIGATUS PHYTASE STRUCTURE IMPROVES THE THERMOSTABILITY OF ASPERGILLUS NIGER PHYA PHYTASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although it has been widely used as a feed supplement to reduce manure phosphorus pollution of swine and poultry, Aspergillus niger PhyA phytase is unable to withstand heat inactivation during feed pelleting. Crystal structure comparisons with its close homolog, the thermostable Aspergillus fumigatu...

  2. Cloning and Characterization of the Aspergillus ochraceoroseus Aflatoxin Biosynthetic Gene Cluster

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Production of the carcinogenic mycotoxin aflatoxin B1 has been reported from members of Aspergillus section Flavi, Aspergillus section Nidulantes, and a newly proposed section, Aspergillus section Ochraceorosei that consists of Aspergillus ochraceoroseus and the closely related A. rambellii. A. och...

  3. Complete Makeover

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site]

    Released July 23, 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth.

    Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms.

    We finish our look at Mars's dynamic atmosphere with an image of the surface that has been completely modified by the wind. Even the small ridges that remain have been ground down to a cliff-face with a 'tail' of eroded material. The crosshatching shows that the wind regime has remained mainly E/W to ENE/WSW.

    Image information: VIS instrument. Latitude 8.9, Longitude 221 East (139 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip

  4. [Cerebral Aspergillus abscess in immunocompetent patient].

    PubMed

    Pianetti Filho, Geraldo; Pedroso, Enio Roberto Pietra; Giannetti, Alexandre Varela; Darwich, Rogério

    2005-12-01

    We report an unusual case of brain aspergillosis with multiple recurrent abscess in a 40 year-old immunocompetent woman, with good therapeutical outcome. The patient presented a subarachnoid hemorrhage caused by a ruptured pericallosal artery aneurysm and was submitted to a craniotomy for aneurysm surgery. Five months later, she developed multiple Aspergillus cerebral abscess. Two craniotomies and amphotericin B became necessary during treatment. Fourteen years later, she is asymptomatic. Treatment of brain aspergillosis abscess implied the combination of both surgical and drug therapy with amphotericin B. PMID:16400435

  5. An H1-H3 chimeric influenza virosome confers complete protection against lethal challenge with PR8 (H1N1) and X47 (H3N2) viruses in mice.

    PubMed

    Abdoli, Asghar; Soleimanjahi, Hoorieh; Tavassoti Kheiri, Masoumeh; Jamali, Abbas; Mazaheri, Vahideh; Abdollahpour Alitappeh, Meghdad

    2014-12-01

    Annual health threats and economic damages caused by influenza virus are still a main concern of the World Health Organization and other health departments all over the world. An influenza virosome is a highly efficient immunomodulating carrier mimicking the natural antigen presentation pathway and has shown an excellent tolerability profile due to its biocompatibility and purity. The major purpose of this study was to construct a new chimeric virosome influenza vaccine containing hemagglutinin (HA) and neuraminidase (NA) proteins derived from the A/PR/8/1934 (H1N1) (PR8) and A/X/47 (H3N2) (X47) viruses, and to evaluate its efficacy as a vaccine candidate in mice. A single intramuscular vaccination with the chimeric virosomes provided complete protection against lethal challenge with the PR8 and X47 viruses. The chimeric virosomes induced high IgG antibody responses as well as hemagglutination inhibition (HAI) titers. HAI titers following the chimeric virosome vaccination were at the same level as the whole inactivated influenza vaccine. Mice immunized with the chimeric virosomes displayed considerably less weight loss and exhibited significantly reduced viral load in their lungs compared with the controls. The chimeric virosomes can be used as an innovative vaccine formulation to confer protection against a broad range of influenza viruses. PMID:25066138

  6. Scleral Buckle Infection with Aspergillus Flavus

    PubMed Central

    Bouhaimed, Manal; Al-Dhibi, Hassan; Al-Assiri, Abdullah

    2008-01-01

    Purpose: To present a case of scleral buckle infection with Aspergillus flavus in a tertiary eye center in Saudi Arabia. Methods: A retrospective case report of a 28-year-old Saudi male who presented with a six-month history of conjunctival injection and discharge from the left eye which had undergone uncomplicated conventional retinal detachment surgery, at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, in the form of cryopexy, subretinal fluid drainage and scleral buckle (grooved segmental sponge and circumferential band with sleeve) for a macula on retinal detachment four years earlier. A diagnosis of infected extruded scleral buckle was made and the buckle was removed. Results: The infected scleral buckle was removed under local anesthesia with administration of sub-conjunctival irrigation of 50 mg solution of Vancomycin, and sub-conjunctival injection of 25mg of Vancomycin. Post operative microbiological studies revealed infection with silver staining of moderate Aspergillus flavus hyphae. Visual acuity of the left eye improved from 20/200 before surgery to 20/60 in the two years follow-up visit. Conclusion: This case report indicates the importance of considering infection with multiple organisms – including fungal ones – in cases of scleral buckle infections in our population. PMID:20379425

  7. 2-hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species.

    PubMed

    Sakko, M; Moore, C; Novak-Frazer, L; Rautemaa, V; Sorsa, T; Hietala, P; Järvinen, A; Bowyer, P; Tjäderhane, L; Rautemaa, R

    2014-04-01

    The amino acid derivative 2-hydroxyisocaproic acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml(-1) . Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml(-1) was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy. As a fungicidal agent with broad-spectrum bactericidal activity, it may be useful in the topical treatment of multispecies superficial infections. PMID:24125484

  8. Use of UHPLC high resolution Orbitrap mass spectrometry to investigate genes involved in the production of secondary metabolites in Aspergillus flavus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fungus Aspergillus flavus is known for its ability to produce the toxic and carcinogenic aflatoxins in food and feed. While aflatoxins are of most concern, A. flavus is predicted to be capable of producing many more metabolites based on a study of its complete genome sequence. Some of these meta...

  9. Pathway of Glycine Betaine Biosynthesis in Aspergillus fumigatus

    PubMed Central

    Lambou, Karine; Pennati, Andrea; Valsecchi, Isabel; Tada, Rui; Sherman, Stephen; Sato, Hajime; Beau, Remi

    2013-01-01

    The choline oxidase (CHOA) and betaine aldehyde dehydrogenase (BADH) genes identified in Aspergillus fumigatus are present as a cluster specific for fungal genomes. Biochemical and molecular analyses of this cluster showed that it has very specific biochemical and functional features that make it unique and different from its plant and bacterial homologs. A. fumigatus ChoAp catalyzed the oxidation of choline to glycine betaine with betaine aldehyde as an intermediate and reduced molecular oxygen to hydrogen peroxide using FAD as a cofactor. A. fumigatus Badhp oxidized betaine aldehyde to glycine betaine with reduction of NAD+ to NADH. Analysis of the AfchoAΔ::HPH and AfbadAΔ::HPH single mutants and the AfchoAΔAfbadAΔ::HPH double mutant showed that AfChoAp is essential for the use of choline as the sole nitrogen, carbon, or carbon and nitrogen source during the germination process. AfChoAp and AfBadAp were localized in the cytosol of germinating conidia and mycelia but were absent from resting conidia. Characterization of the mutant phenotypes showed that glycine betaine in A. fumigatus functions exclusively as a metabolic intermediate in the catabolism of choline and not as a stress protectant. This study in A. fumigatus is the first molecular, cellular, and biochemical characterization of the glycine betaine biosynthetic pathway in the fungal kingdom. PMID:23563483

  10. Novel regulation of aflatoxin B1 biosynthesis in Aspergillus flavus by piperonal.

    PubMed

    Park, Eun-Sil; Bae, In Kyung; Kim, Ho Jin; Lee, Sung-Eun

    2016-08-01

    The present study investigated its inhibitory role in aflatoxin (AF) biosynthesis. Treating only AFB1- and B2-producing Aspergillus flavus with piperonal completely inhibited AFB1 production with high sclerotial formation, resulting in 20-fold higher AFG2 production. On the other hand, benzodioxole and eugenol suppressed AFB1 production without AFG formation, while methyleugenol showed potent inhibition of AFB1 production with slight production of AFG1. These results indicate that natural products may change aflatoxin biosynthesis, and highlight a novel regulation of AFG2 production by piperonal. It is the first report for chemical regulation on AFG2 production in non-AFG producing-aspergilli. PMID:26273991

  11. Crystallization and diffraction analysis of [beta]-N-acetylhexosaminidase from Aspergillus oryzae

    SciTech Connect

    Vanek, Ondrej; Brynd, Jirí; Hofbauerová, Katerina; Kukack, Zdenek; Pachl, Petr; Bezouska, Karel; Rezácová, Pavlína

    2012-05-08

    Fungal {beta}-N-acetylhexosaminidases are enzymes that are used in the chemoenzymatic synthesis of biologically interesting oligosaccharides. The enzyme from Aspergillus oryzae was produced and purified from its natural source and crystallized using the hanging-drop vapor-diffusion method. Diffraction data from two crystal forms (primitive monoclinic and primitive tetragonal) were collected to resolutions of 3.2 and 2.4 {angstrom}, respectively. Electrophoretic and quantitative N-terminal protein-sequencing analyses confirmed that the crystals are formed by a complete biologically active enzyme consisting of a glycosylated catalytic unit and a noncovalently attached propeptide.

  12. Pulmonary hypersensitivity to Alternaria and Aspergillus in baker's asthma.

    PubMed

    Klaustermeyer, W B; Bardana, E J; Hale, F C

    1977-05-01

    In two cases of baker's asthma pulmonary hypersensitivity was found to the fungi Alternaria and Aspergillus. Provocative bronchial challenge revealed a dual response; an immediate and an Arthus type hypersensitivity to Aspergillus in the first case. A primary binding assay revealed high titres of anti-Aspergillus antibody in the serum. In the second case intradermal and bronchial challenge suggested an immediate type I hypersensitivity response to Alternaria. The suspected organisms were present in the room air of the bakeries. It is suggested that an immunological response to these airborne fungi may have contributed to the pathogenesis of baker's asthma. PMID:561668

  13. Effect of gamma radiation on Aspergillus flavus and Aspergillus ochraceus ultrastructure and mycotoxin production

    NASA Astrophysics Data System (ADS)

    Ribeiro, J.; Cavaglieri, L.; Vital, H.; Cristofolini, A.; Merkis, C.; Astoreca, A.; Orlando, J.; Carú, M.; Dalcero, A.; Rosa, C. A. R.

    2011-05-01

    The aim of this work was to study the effect of gamma radiation (2 kGy) on Aspergillus flavus and Aspergillus ochraceus ultrastructure. Moreover, the influence on aflatoxin B 1 and ochratoxin A production was also observed. Irradiated A. flavus strain showed a dull orangish colony while control strain showed the typical green color. Minor differences were observed on stipes, metulae and conidia size between control and irradiated A. flavus and A. ochraceus strains. Irradiated fungi showed ultrastructural changes on cell wall, plasmalema and cytoplasm levels. The levels of mycotoxins produced by irradiated strains were two times greater than those produced by control strains. Successive transferences of irradiated strains on malt extract agar allowed the fungus to recuperate morphological characteristics. Although minor changes in the fungal morphology were observed, ultrastructural changes at cell wall level and the increase of mycotoxin production ability were observed. Inappropriate storage of irradiated food and feed would allow the development of potentially more toxicogenic fungal propagules.

  14. Characterization and biotechnological application of recombinant xylanases from Aspergillus nidulans.

    PubMed

    Maitan-Alfenas, Gabriela P; Oliveira, Mariana B; Nagem, Ronaldo A P; de Vries, Ronald P; Guimarães, Valéria M

    2016-10-01

    Two xylanases from Aspergillus nidulans, XlnB and XlnC, were expressed in Pichia pastoris, purified and characterized. XlnB and XlnC achieved maximal activities at 60°C and pH 7.5 and at 50°C and pH 6.0, respectively. XlnB showed to be very thermostable by maintaining 50% of its original activity after 49h incubated at 50°C. XlnB had its highest activity against wheat arabinoxylan while XlnC had the best activity against beechwood xylan. Both enzymes were completely inhibited by SDS and HgCl2. Xylotriose at 1mg/ml also totally inibited XlnB activity. TLC analysis showed that the main product of beechwood xylan hydrolysis by XlnB and XlnC was xylotetraose. An additive effect was shown between XlnB and XlnC and the xylanases of two tested commercial cocktails. Sugarcane bagasse saccharification results showed that these two commercial enzymatic cocktails were able to release more glucose and xylose after supplementation with XlnB and XlnC. PMID:27235731

  15. Aspergillus Enzymes Involved in Degradation of Plant Cell Wall Polysaccharides

    PubMed Central

    de Vries, Ronald P.; Visser, Jaap

    2001-01-01

    Degradation of plant cell wall polysaccharides is of major importance in the food and feed, beverage, textile, and paper and pulp industries, as well as in several other industrial production processes. Enzymatic degradation of these polymers has received attention for many years and is becoming a more and more attractive alternative to chemical and mechanical processes. Over the past 15 years, much progress has been made in elucidating the structural characteristics of these polysaccharides and in characterizing the enzymes involved in their degradation and the genes of biotechnologically relevant microorganisms encoding these enzymes. The members of the fungal genus Aspergillus are commonly used for the production of polysaccharide-degrading enzymes. This genus produces a wide spectrum of cell wall-degrading enzymes, allowing not only complete degradation of the polysaccharides but also tailored modifications by using specific enzymes purified from these fungi. This review summarizes our current knowledge of the cell wall polysaccharide-degrading enzymes from aspergilli and the genes by which they are encoded. PMID:11729262

  16. Mapping the polysaccharide degradation potential of Aspergillus niger

    PubMed Central

    2012-01-01

    Background The degradation of plant materials by enzymes is an industry of increasing importance. For sustainable production of second generation biofuels and other products of industrial biotechnology, efficient degradation of non-edible plant polysaccharides such as hemicellulose is required. For each type of hemicellulose, a complex mixture of enzymes is required for complete conversion to fermentable monosaccharides. In plant-biomass degrading fungi, these enzymes are regulated and released by complex regulatory structures. In this study, we present a methodology for evaluating the potential of a given fungus for polysaccharide degradation. Results Through the compilation of information from 203 articles, we have systematized knowledge on the structure and degradation of 16 major types of plant polysaccharides to form a graphical overview. As a case example, we have combined this with a list of 188 genes coding for carbohydrate-active enzymes from Aspergillus niger, thus forming an analysis framework, which can be queried. Combination of this information network with gene expression analysis on mono- and polysaccharide substrates has allowed elucidation of concerted gene expression from this organism. One such example is the identification of a full set of extracellular polysaccharide-acting genes for the degradation of oat spelt xylan. Conclusions The mapping of plant polysaccharide structures along with the corresponding enzymatic activities is a powerful framework for expression analysis of carbohydrate-active enzymes. Applying this network-based approach, we provide the first genome-scale characterization of all genes coding for carbohydrate-active enzymes identified in A. niger. PMID:22799883

  17. A novel fungal fruiting structure formed by Aspergillus niger and Aspergillus carbonarius in grape berries.

    PubMed

    Pisani, Cristina; Nguyen, Trang Thoaivan; Gubler, Walter Douglas

    2015-09-01

    Sour rot, is a pre-harvest disease that affects many grape varieties. Sour rot symptoms include initial berry cracking and breakdown of berry tissue. This is a disease complex with many filamentous fungi and bacteria involved, but is usually initiated by Aspergillus niger or Aspergillus carbonarius. Usually, by the time one sees the rot there are many other organisms involved and it is difficult to attribute the disease to one species. In this study two species of Aspergillus were shown to produce a previously unknown fruiting structure in infected berries. The nodulous morphology, bearing conidia, suggests them to be an 'everted polymorphic stroma'. This structure forms freely inside the berry pulp and assumes multiple shapes and sizes, sometimes sclerotium-like in form. It is composed of a mass of vegetative hyphae with or without tissue of the host containing spores or fruiting bodies bearing spores. Artificially inoculated berries placed in soil in winter showed the possible overwintering function of the fruiting body. Inoculated berry clusters on standing vines produced fruiting structures within 21 d post inoculation when wounds were made at veraison or after (July-September). Histological studies confirmed that the fruiting structure was indeed fungal tissue. PMID:26321727

  18. Extrolites of Aspergillus fumigatus and Other Pathogenic Species in Aspergillus Section Fumigati

    PubMed Central

    Frisvad, Jens C.; Larsen, Thomas O.

    2016-01-01

    Aspergillus fumigatus is an important opportunistic human pathogen known for its production of a large array of extrolites. Up to 63 species have been described in Aspergillus section Fumigati, some of which have also been reliably reported to be pathogenic, including A. felis, A. fischeri, A. fumigatiaffinis, A. fumisynnematus, A. hiratsukae, A. laciniosus, A. lentulus, A. novofumigatus, A. parafelis, A. pseudofelis, A. pseudoviridinutans, A. spinosus, A. thermomutatus, and A. udagawae. These species share the production of hydrophobins, melanins, and siderophores and ability to grow well at 37°C, but they only share some small molecule extrolites, that could be important factors in pathogenicity. According to the literature gliotoxin and other exometabolites can be contributing factors to pathogenicity, but these exometabolites are apparently not produced by all pathogenic species. It is our hypothesis that species unable to produce some of these metabolites can produce proxy-exometabolites that may serve the same function. We tabulate all exometabolites reported from species in Aspergillus section Fumigati and by comparing the profile of those extrolites, suggest that those producing many different kinds of exometabolites are potential opportunistic pathogens. The exometabolite data also suggest that the profile of exometabolites are highly specific and can be used for identification of these closely related species. PMID:26779142

  19. Analysis of Aspergillus nidulans conidial antigens and their prevalence in other Aspergillus species.

    PubMed Central

    Puente, P; Ovejero, M C; Fernández, N; Leal, F

    1991-01-01

    Aspergillus nidulans is an ascomycetous fungus that reproduces asexually by forming multicellular conidiophores and uninucleate spores called conidia. These elements constitute the main vehicle for the transmission of this and other pathogenic Aspergillus species and are the starting point of the different forms of aspergillosis. In order to use A. nidulans as a potential source of useful antigens for the immunodiagnosis of these diseases, we have examined the total protein composition of conidial extracts of this fungus by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis in gels of different percent T. Injection of SDS-extracted conidial proteins into rabbits allowed us to raise a battery of polyclonal antibodies which have defined some important immunogenic polypeptides. Several of these immunogens were both present in mycelial extracts and recognized by antimycelium antibodies. Four of them, designated cdA, cdB, cdC, and cdE, were also found in conidial extracts of other pathogenic Aspergillus species. Only cdE was undetectable in cell extracts of the nonrelated species Fusarium culmorum and Phycomyces blakesleeanus. Images PMID:1937806

  20. Septic arthritis due to tubercular and Aspergillus co-infection.

    PubMed

    Kumar, Mukesh; Thilak, Jai; Zahoor, Adnan; Jyothi, Arun

    2016-01-01

    Aspergillus septic arthritis is a rare and serious medical and surgical problem. It occurs mainly in immunocompromised patients. Aspergillus fumigatus is the most common causative organism followed by Aspergillus flavus. The most common site affected is knee followed by shoulder, ankle, wrist, hip and sacroiliac joint. Debridement and voriconazole are primary treatment of articular aspergilosis. To the best of our knowledge, there are no reported cases of co-infection of tuberculosis (TB) and Aspergillus infecting joints. We report a case of co-infection of TB and A. flavus of hip and knee of a 60-year-old male, with type 2 diabetes mellitus. He was treated with debridement, intravenous voriconazole, and antitubercular drugs. PMID:27293296

  1. Nutrient environment influences competition among Aspergillus flavus genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Structures of Aspergillus flavus populations, shaped by intraspecific competition, influence the incidences and severities of crop aflatoxin contamination. Competition for nutrients may be one factor modulating intraspecific interactions, but influences of specific types and concentrations of nutrie...

  2. Sexual reproduction in aflatoxin-producing Aspergillus nomius

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sexual reproduction was examined in the aflatoxin-producing fungus Aspergillus nomius. Crosses between sexually compatible strains resulted in the formation of multiple nonostiolate ascocarps within stromata, which places the teleomorph in the genus Petromyces. Ascocarp and ascospore morphology in...

  3. Microbial transformation of curcumol by Aspergillus niger.

    PubMed

    Chen, Li-Xia; Zhang, Hui; Zhao, Qian; Yin, Shi-Yu; Zhang, Zhong; Li, Tian-Xian; Qiu, Feng

    2013-02-01

    Curcumol is a representative index component for the quality control of the essential oil of Curcuma wenyujin Y.H. Chen et C. Ling, an antivirus and anticancer drug in China. Microbial transformation of curcumol (1) by Aspergillus niger AS 3.739 yielded two products. Their structures were elucidated as 3alpha-hydroxycurcumol (2) and 3alpha-(4'-methoxy-succinyloxy)-curcumol (3) by extensive spectroscopic methods including 2D-NMR and HRESI-MS. Among them, 3 is a new compound. Esterification of the substrate with succinic acid is a novel reaction in the field of microbial transformation of natural products. Compound 2, the major transformation product of 1, was a high regio- and stereo-specific hydroxylation product and showed significant antiviral effects. PMID:23513713

  4. Environmental fungicides and triazole resistance in Aspergillus.

    PubMed

    Bowyer, Paul; Denning, David W

    2014-02-01

    Fungal diseases are problematic in both human health and agriculture. Treatment options are limited and resistance may emerge. The relatively recent recognition of triazole resistance in Aspergillus fumigatus has prompted questioning of the origin of resistance. While multiple mechanisms are described in clinical isolates from triazole-treated patients, some de novo resistance is also recognised, especially attributable to TR34 /L98H. Such strains probably arose in the environment, and, indeed, multiple studies have now demonstrated TR(34) /L98H triazole resistance strains of A. fumigatus from soil. Docking and other in vitro studies are consistent with environmental resistance induction through exposure to certain triazole fungicides, notably difenoconazole, propiconazole, epoxiconazole, bromuconazole and tebuconazole. This article addresses the potential implications of this issue for both human health and food security. PMID:23616354

  5. A tyrosinase inhibitor from Aspergillus niger.

    PubMed

    Vasantha, K Y; Murugesh, C S; Sattur, A P

    2014-10-01

    Tyrosinase, in the presence of oxygen, is the main culprit in post harvest browning of food products, resulting in the drop in its commercial value. In an effort to seek natural tyrosinase inhibitors for food applications, a screening programme was undertaken. Of the 26 fungal cultures isolated from soil samples of Agumbe forest, India, one isolate S16, identified as Aspergillus niger, gave an inhibition of 84 % against the enzyme. The inhibitor was isolated by following an enzyme inhibition assay guided purification protocol. The structure of the inhibitor was elucidated and found to be kojic acid. The IC50 of the Competitive inhibitor was found to be 8.8 μg with a Ki of 0.085 mM. PMID:25328242

  6. Regulation of plant biomass utilization in Aspergillus.

    PubMed

    Kowalczyk, Joanna E; Benoit, Isabelle; de Vries, Ronald P

    2014-01-01

    The ability of fungi to survive in every known biotope, both natural and man-made, relies in part on their ability to use a wide range of carbon sources. Fungi degrade polymeric carbon sources present in the environment (polysaccharides, proteins, and lignins) to use the monomeric components as nutrients. However, the available carbon sources vary strongly in nature, both between biotopes and in time. The degradation of polymeric carbon sources is mediated through the production of a broad range of enzymes, the production of which is tightly controlled by a network of regulators and linked to the activation of catabolic pathways to convert the released monomers. This review summarizes the knowledge of Aspergillus regulators involved in plant biomass utilization. PMID:24767425

  7. Toxic Metabolite Produced by Aspergillus wentii

    PubMed Central

    Wu, M. T.; Ayres, J. C.; Koehler, P. E.; Chassis, G.

    1974-01-01

    Mycelial extracts of an Aspergillus wentii strain grown on yeast-extract sucrose medium and initially isolated from country-cured ham were highly toxic when inoculated into chicken embryos or fed to mice. Moldy corn and rice were less toxic when fed to mice. Water extracts of moldy corn or rice or culture filtrates from yeast-extract sucrose medium were not toxic. Purification by thin-layer chromatography followed by crystallization yielded orange-red crystals that showed high toxicity and had a melting point of 285 to 286 C. Chloroform solutions of the crystals had absorption maxima at 270, 295, and 452 nm. The smallest amount of this component necessary to have zero hatchability of fertile eggs was 50 μg/egg. PMID:4823420

  8. Aspergillus mycotic aneurysm--case report.

    PubMed

    Komatsu, Y; Narushima, K; Kobayashi, E; Tomono, Y; Nose, T

    1991-06-01

    A 61-year-old female developed subarachnoid hemorrhage after trans-sphenoidal surgery for Rathke's cleft cyst. Neuroradiological examination revealed a large aneurysm at the C1 portion of the right internal carotid artery. Autopsy revealed marked proliferation of aspergillus hyphae in the wall of the aneurysm. A review of previously reported cases of fungal aneurysm proposes two developmental processes. Aneurysms secondary to fungal meningitis tend to be large in size and located in the major cerebral artery trunk, but aneurysms following fungal sepsis tend to be small and in peripheral branches. The former aneurysms are probably caused by fungus invasion into the intracranium, usually from the paranasal sinus, and the latter may be due to fungal emboli like bacterial emboli in bacterial endocarditis. Ruptured fungal aneurysms are difficult to treat, so fungal meningitis or sepsis must be eradicated before an aneurysm develops. PMID:1724300

  9. Aspergillus Thyroiditis after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Ataca, Pinar; Atilla, Erden; Saracoglu, Pelin; Yilmaz, Gulden; Civriz Bozdag, Sinem; Toprak, Selami Kocak; Yuksel, Meltem Kurt; Ceyhan, Koray; Topcuoglu, Pervin

    2015-01-01

    Aspergillus thyroiditis is a rare disorder detected in immunocompromised patients during disseminated infections. Early management is essential to prevent high mortality. A 61-year-old allogeneic stem cell male recipient presented with painful thyroid nodular enlargement. He had low TSH and low free T4 levels. The thyroid ultrasound showed a hypoechoic nodule; biopsy indicated suppurative Aspergillus thyroiditis. He was successfully treated by amphotericin B. PMID:26640727

  10. Primary cutaneous aspergillosis due to Aspergillus tamarii in an immunocompetent host

    PubMed Central

    Sharma, Sadhna; Yenigalla, Bindu Madhav; Naidu, Sujeet Kumar; Pidakala, Premalatha

    2013-01-01

    Primary cutaneous aspergillosis is a rare disease usually caused by Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus and Aspergillus ustus. It is usually seen in immunocompromised hosts, though some cases are also reported in immunocompetent hosts. We present a case of an immunocompetent farmer who presented with generalised nodules and plaques, mimicking erythema nodosum leprosum but turned out to be cutaneous aspergillosis caused by Aspergillus tamarii. The characteristic ascospores of Aspergillus species were found in skin lesions on fungus isolated in culture. The patient showed excellent response to antifungal therapy. PMID:23970496

  11. Identification and Characterization of Aspergillus Nidulans Mutants Defective in Cytokinesis

    PubMed Central

    Harris, S. D.; Morrell, J. L.; Hamer, J. E.

    1994-01-01

    Filamentous fungi undergo cytokinesis by forming crosswalls termed septa. Here, we describe the genetic and physiological controls governing septation in Aspergillus nidulans. Germinating conidia do not form septa until the completion of their third nuclear division. The first septum is invariantly positioned at the basal end of the germ tube. Block-and-release experiments of nuclear division with benomyl or hydroxyurea, and analysis of various nuclear division mutants demonstrated that septum formation is dependent upon the third mitotic division. Block-and-release experiments with cytochalasin A and the localization of actin in germlings by indirect immunofluorescence showed that actin participated in septum formation. In addition to being concentrated at the growing hyphal tips, a band of actin was also apparent at the site of septum formation. Previous genetic analysis in A. nidulans identified four genes involved in septation (sepA-D). We have screened a new collection of temperature sensitive (ts) mutants of A. nidulans for strains that failed to form septa at the restrictive temperature but were able to complete early nuclear divisions. We identified five new genes designated sepE, G, H, I and J, along with one additional allele of a previously identified septation gene. On the basis of temperature shift experiments, nuclear counts and cell morphology, we sorted these cytokinesis mutants into three phenotypic classes. Interestingly, one class of mutants fails to form septa and fails to progress past the third nuclear division. This class of mutants suggests the existence of a regulatory mechanism in A. nidulans that ensures the continuation of nuclear division following the initiation of cytokinesis. PMID:8150280

  12. Biosynthetic Pathway of the Reduced Polyketide Product Citreoviridin in Aspergillus terreus var. aureus Revealed by Heterologous Expression in Aspergillus nidulans.

    PubMed

    Lin, Tzu-Shyang; Chiang, Yi-Ming; Wang, Clay C C

    2016-03-18

    Citreoviridin (1) belongs to a class of F1-ATPase β-subunit inhibitors that are synthesized by highly reducing polyketide synthases. These potent mycotoxins share an α-pyrone polyene structure, and they include aurovertin, verrucosidin, and asteltoxin. The identification of the citreoviridin biosynthetic gene cluster in Aspergillus terreus var. aureus and its reconstitution using heterologous expression in Aspergillus nidulans are reported. Two intermediates were isolated that allowed the proposal of the biosynthetic pathway of citreoviridin. PMID:26954888

  13. Interplay between Gliotoxin Resistance, Secretion, and the Methyl/Methionine Cycle in Aspergillus fumigatus

    PubMed Central

    Owens, Rebecca A.; O'Keeffe, Grainne; Smith, Elizabeth B.; Dolan, Stephen K.; Hammel, Stephen; Sheridan, Kevin J.; Fitzpatrick, David A.; Keane, Thomas M.

    2015-01-01

    Mechanistic studies on gliotoxin biosynthesis and self-protection in Aspergillus fumigatus, both of which require the gliotoxin oxidoreductase GliT, have revealed a rich landscape of highly novel biochemistries, yet key aspects of this complex molecular architecture remain obscure. Here we show that an A. fumigatus ΔgliA strain is completely deficient in gliotoxin secretion but still retains the ability to efflux bisdethiobis(methylthio)gliotoxin (BmGT). This correlates with a significant increase in sensitivity to exogenous gliotoxin because gliotoxin trapped inside the cell leads to (i) activation of the gli cluster, as disabling gli cluster activation, via gliZ deletion, attenuates the sensitivity of an A. fumigatus ΔgliT strain to gliotoxin, thus implicating cluster activation as a factor in gliotoxin sensitivity, and (ii) increased methylation activity due to excess substrate (dithiol gliotoxin) for the gliotoxin bis-thiomethyltransferase GtmA. Intracellular dithiol gliotoxin is oxidized by GliT and subsequently effluxed by GliA. In the absence of GliA, gliotoxin persists in the cell and is converted to BmGT, with levels significantly higher than those in the wild type. Similarly, in the ΔgliT strain, gliotoxin oxidation is impeded, and methylation occurs unchecked, leading to significant S-adenosylmethionine (SAM) depletion and S-adenosylhomocysteine (SAH) overproduction. This in turn significantly contributes to the observed hypersensitivity of gliT-deficient A. fumigatus to gliotoxin. Our observations reveal a key role for GliT in preventing dysregulation of the methyl/methionine cycle to control intracellular SAM and SAH homeostasis during gliotoxin biosynthesis and exposure. Moreover, we reveal attenuated GliT abundance in the A. fumigatus ΔgliK strain, but not the ΔgliG strain, following exposure to gliotoxin, correlating with relative sensitivities. Overall, we illuminate new systems interactions that have evolved in gliotoxin-producing, compared

  14. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

    SciTech Connect

    Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus.

  15. Could biorational insecticides be used in the management of aflatoxigenic Aspergillus parasiticus and its insect vectors in stored wheat?

    PubMed Central

    Khan, Tiyyabah; Shahid, Ahmad Ali

    2016-01-01

    Insect pests in stored wheat cause significant losses and play an important role in the dispersal of viable fungal spores of various species including aflatoxin producing Aspergillus parasiticus. The problem of insecticide resistance in stored insects and environmental hazards associated with fumigants and conventional grain protectants underscore the need to explore reduced risk insecticides to control stored insects with the ultimate effect on aflatoxin production. The purpose of this study was to investigate the insecticidal potential of four biorational insecticides: spinosad, thiamethoxam, imidacloprid and indoxacarb, on wheat grains artificially infested with Rhyzopertha dominica/Sitophilus oryzae and/or A. parasiticus spores, and the subsequent effect on aflatoxin production. Spinosad and thiamethoxam were the most effective insecticides against R. dominica compared to S. oryzae followed by imidacloprid. Spinosad applied at 0.25–1 ppm and thiamethoxam at 2 and 4 ppm concentrations resulted in complete mortality of R. dominica. However, indoxacarb was more toxic against S. oryzae compared to R. dominica. Wheat grains inoculated with R. dominica/S. oryzae +spores elicited higher aflatoxin levels than wheat grains inoculated with or without insecticide+spores. In all the treatment combinations containing insects, aflatoxin production was dependent on insects’ survival rate. In addition, thiamethoxam and imidacloprid had also a significant direct effect on reducing aflatoxin production. Aflatoxin levels were lower in the treatment combinations with any concentration of thiamethoxam/imidacloprid+spores as compared to wheat grains inoculated with spores only. Correlation analyses revealed highly significant and positive association between moisture contents/insect survival rate and production of aflatoxin levels, and insect survival rate and moisture contents of the wheat grains. In conclusion, the results of the present study provide baseline data on the use

  16. Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

    PubMed Central

    Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

    2013-01-01

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

  17. Sexual structures in Aspergillus: morphology, importance and genomics.

    PubMed

    Geiser, David M

    2009-01-01

    The genus Aspergillus comprises a few hundred species sharing a common asexual spore forming structure, the aspergillum. Approximately one-third of these species also produce a sexual stage, all but five of which are known to be homothallic. Sexual stages associated with Aspergillus fall into approximately ten different genera, reflecting a tremendous degree of phylogenetic and biological diversity. Sexual stages in Aspergillus are plectomycetous, typical for the order in which it resides, the Eurotiales. Theoretically, a homothallic Aspergillus species can produce both asexual conidia and sexual ascospores in both clonal and recombinant fashion, although the actual significance of these potential modes of reproduction is unclear. Aspergillus species with known sexual stages tend to be minor players in infections of humans, perhaps because of their tendency to produce fewer asexual spores compared to their non-teleomorphic congeners. The discovery of population genetic and genomic evidence for sex in species with no known sexual stage indicates that no assumptions can be made about the clonal versus recombinant life histories of a species based on its known mitotic and/or meiotic reproductive modes. PMID:18608901

  18. Shedding light on Aspergillus niger volatile exometabolome

    PubMed Central

    Costa, Carina Pedrosa; Gonçalves Silva, Diogo; Rudnitskaya, Alisa; Almeida, Adelaide; Rocha, Sílvia M.

    2016-01-01

    An in-depth exploration of the headspace content of Aspergillus niger cultures was performed upon different growth conditions, using a methodology based on advanced multidimensional gas chromatography. This volatile fraction comprises 428 putatively identified compounds distributed over several chemical families, being the major ones hydrocarbons, alcohols, esters, ketones and aldehydes. These metabolites may be related with different metabolic pathways, such as amino acid metabolism, biosynthesis and metabolism of fatty acids, degradation of aromatic compounds, mono and sesquiterpenoid synthesis and carotenoid cleavage. The A. niger molecular biomarkers pattern was established, comprising the 44 metabolites present in all studied conditions. This pattern was successfully used to distinguish A. niger from other fungi (Candida albicans and Penicillium chrysogenum) with 3 days of growth by using Partial Least Squares-Discriminant Analysis (PLS-DA). In addition, PLS-DA-Variable Importance in Projection was applied to highlight the metabolites playing major roles in fungi distinction; decreasing the initial dataset to only 16 metabolites. The data pre-processing time was substantially reduced, and an improvement of quality-of-fit value was achieved. This study goes a step further on A. niger metabolome construction and A. niger future detection may be proposed based on this molecular biomarkers pattern. PMID:27264696

  19. Emergence of Azole Resistance in Aspergillus.

    PubMed

    Wiederhold, Nathan P; Patterson, Thomas F

    2015-10-01

    Resistance to the azole antifungals itraconazole, voriconazole, and posaconazole in Aspergillus species is a growing concern. This is especially alarming for A. fumigatus, where acquired resistance has been documented in patients with invasive disease caused by this species that were exposed to these agents, as well as in azole-naive individuals. The primary mechanisms of resistance that have been described in clinical strains include different point mutations in the CYP51A gene, which encodes the enzyme responsible for converting lanosterol to ergosterol via demethylation. Some resistant isolates also contain a tandem repeat in the promoter region of this gene that causes increased expression. These mutations, including TR34/L98H and TR46/Y121F/T289A have also been found in the environment in several areas of the world and have been demonstrated to cause resistance to azole fungicides used in agriculture, thus raising the concern of environmental spread of resistance. Treatment options are limited in patients with infections caused by azole-resistant isolates and include amphotericin B formulations or combination therapy involving an echinocandin. However, there are few clinical data available to help guide therapy, and infections caused by resistant A. fumigatus isolates have been reported to have high mortality rates. PMID:26398534

  20. Shedding light on Aspergillus niger volatile exometabolome.

    PubMed

    Costa, Carina Pedrosa; Gonçalves Silva, Diogo; Rudnitskaya, Alisa; Almeida, Adelaide; Rocha, Sílvia M

    2016-01-01

    An in-depth exploration of the headspace content of Aspergillus niger cultures was performed upon different growth conditions, using a methodology based on advanced multidimensional gas chromatography. This volatile fraction comprises 428 putatively identified compounds distributed over several chemical families, being the major ones hydrocarbons, alcohols, esters, ketones and aldehydes. These metabolites may be related with different metabolic pathways, such as amino acid metabolism, biosynthesis and metabolism of fatty acids, degradation of aromatic compounds, mono and sesquiterpenoid synthesis and carotenoid cleavage. The A. niger molecular biomarkers pattern was established, comprising the 44 metabolites present in all studied conditions. This pattern was successfully used to distinguish A. niger from other fungi (Candida albicans and Penicillium chrysogenum) with 3 days of growth by using Partial Least Squares-Discriminant Analysis (PLS-DA). In addition, PLS-DA-Variable Importance in Projection was applied to highlight the metabolites playing major roles in fungi distinction; decreasing the initial dataset to only 16 metabolites. The data pre-processing time was substantially reduced, and an improvement of quality-of-fit value was achieved. This study goes a step further on A. niger metabolome construction and A. niger future detection may be proposed based on this molecular biomarkers pattern. PMID:27264696

  1. Nitrification of Aspartate by Aspergillus flavus

    PubMed Central

    Hatcher, H. J.; Schmidt, E. L.

    1971-01-01

    Heterotrophic conversion of l-aspartic acid to nitrification products by Aspergillus flavus was studied in a replacement incubation system. Numerous amino acids supported nitrification; aspartate and glutamate were about equivalent as the best sources of nitrate. Addition of sodium bicarbonate to the incubation system substantially enhanced nitrate formation for all nitrifiable amino acids except aspartic acid, but the basis for the bicarbonate effect is obscure. The yield of nitrate from l-aspartate was not approached by forms of aspartic acid resulting from substitution on the beta carbon, the amino nitrogen, or the gamma carboxyl group or by aspartate presented as the d-configuration. There was no relationship between nitrate formation and the occurrence of such possible intermediates as nitrite, bound hydroxylamine, ammonia, aspergillic acid, and beta-nitropropionic acid. Uniformly labeled 14C-l-aspartate that was nitrified in replacement incubation led to no accumulation of label in possible nitrification products in the culture filtrate. Label was found in components of the mycelium after acid hydrolysis, with heaviest accumulation in what appeared to be glucosamine and an unidentified compound, possibly acetylglucosamine. Detectable label was redistributed into serine, glycine, and threonine. Images PMID:5549699

  2. Apical control of conidiation in Aspergillus nidulans.

    PubMed

    Oiartzabal-Arano, Elixabet; Perez-de-Nanclares-Arregi, Elixabet; Espeso, Eduardo A; Etxebeste, Oier

    2016-05-01

    The infection cycle of filamentous fungi consists of two main stages: invasion (growth) and dispersion (development). After the deposition of a spore on a host, germination, polar extension and branching of vegetative cells called hyphae allow a fast and efficient invasion. Under suboptimal conditions, genetic reprogramming of hyphae results in the generation of asexual spores, allowing dissemination to new hosts and the beginning of a new infection cycle. In the model filamentous fungus Aspergillus nidulans, asexual development or conidiation is induced by the upstream developmental activation (UDA) pathway. UDA proteins transduce signals from the tip, the polarity site of hyphae, to nuclei, where developmental programs are transcriptionally activated. The present review summarizes the current knowledge on this tip-to-nucleus communication mechanism, emphasizing its dependence on hyphal polarity. Future approaches to the topic will also be suggested, as stimulating elements contributing to the understanding of how apical signals are coupled with the transcriptional control of development and pathogenesis in filamentous fungi. PMID:26782172

  3. Genetics of Polyketide Metabolism in Aspergillus nidulans

    PubMed Central

    Klejnstrup, Marie L.; Frandsen, Rasmus J. N.; Holm, Dorte K.; Nielsen, Morten T.; Mortensen, Uffe H.; Larsen, Thomas O.; Nielsen, Jakob B.

    2012-01-01

    Secondary metabolites are small molecules that show large structural diversity and a broad range of bioactivities. Some metabolites are attractive as drugs or pigments while others act as harmful mycotoxins. Filamentous fungi have the capacity to produce a wide array of secondary metabolites including polyketides. The majority of genes required for production of these metabolites are mostly organized in gene clusters, which often are silent or barely expressed under laboratory conditions, making discovery and analysis difficult. Fortunately, the genome sequences of several filamentous fungi are publicly available, greatly facilitating the establishment of links between genes and metabolites. This review covers the attempts being made to trigger the activation of polyketide metabolism in the fungal model organism Aspergillus nidulans. Moreover, it will provide an overview of the pathways where ten polyketide synthase genes have been coupled to polyketide products. Therefore, the proposed biosynthesis of the following metabolites will be presented; naphthopyrone, sterigmatocystin, aspyridones, emericellamides, asperthecin, asperfuranone, monodictyphenone/emodin, orsellinic acid, and the austinols. PMID:24957370

  4. Overexpression of protein disulfide isomerase in Aspergillus.

    PubMed

    El-Adawi, H; Khanh, N Q; Gassen, H

    2000-10-01

    One of the major problems with the production of biotechnologically valuable proteins has been the purification of the product. For Escherichia coli and Saccharomyces cerevisiae, there are several techniques for the purification of intracellular proteins, but these are time consuming and often result in poor yields. Purification can be considerably facilitated, if the product is secreted from the host cell. In the work presented, we have constructed an expression vector (pSGNH2) for the secretion of protein disulfide isomerase (PDI; EC 5.3.4.1) from Aspergillus niger, in which the retention signal His-Asp-Glu-Leu (H-D-E-L) was modified to Ala-Leu-Glu-Gln (A-L-E-Q) via the polymerase chain reaction (PCR) method. The PDI gene was placed under the control of the A. oryzae alpha-amylase promoter. This expression vector was transformed into A. niger NRRL3, resulting in PDI secretion into the medium. The catalytic activity of overexpressed PDI from A. niger was indistinguishable from that of PDI isolated from bovine liver. With further strain improvement and optimization of culture conditions, it could be possible to raise the PDI production to the bioprocessing scale. PMID:10977899

  5. Sexual origins of British Aspergillus nidulans isolates.

    PubMed Central

    Geiser, D M; Arnold, M L; Timberlake, W E

    1994-01-01

    Aspergillus nidulans is a holomorphic fungus, capable of producing both meiotically and mitotically derived spores. Meiosis may be an evolutionary relic in this species because it is potentially capable of mitotic recombination and because most Aspergilli lack the ability to produce meiotic spores. We tested the null hypothesis that meiosis has been a major factor in the origin of strains of A. nidulans from Great Britain by estimating linkage disequilibrium among restriction fragment length polymorphisms. These strains belong to different heterokaryon compatibility groups and are thus incapable of undergoing mitotic recombination with one another, so any recombination evidenced by linkage equilibrium is assumed to be the result of meiosis. Eleven cosmid clones of known chromosomal origin were used to generate multilocus genotypes based on restriction-pattern differences for each heterokaryon compatibility group. Low levels of genetic variation and little linkage disequilibrium were found, indicating that the heterokaryon compatibility groups represent recently diverged lineages that arose via meiotic recombination. The null hypothesis that loci are independent could not be rejected. Additionally, low levels of electrophoretic karyotype variation were indicative of meiosis. We conclude that although A. nidulans probably propagates in a primarily clonal fashion, recombination events are frequent enough to disrupt the stable maintenance of clonal genotypes. We further conclude that the British heterokaryon compatibility groups arose via recombination and not through novel mutation. Images PMID:7907796

  6. Comparative Genomics of Aspergillus flavus and A. oryzae: An Early View

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus produces aflatoxins and is the second leading cause of aspergillosis in immunocompromised individuals. Aspergillus oryzae, on the other hand, has been used for centuries in Japan for the fermentation of food. The recently available whole genome sequences of Aspergillus flavus an...

  7. Distribution and conformation of crystalline nigeran in hyphal walls of Aspergillus niger and Aspergillus awamori.

    PubMed Central

    Bobbitt, T F; Nordin, J H; Roux, M; Revol, J F; Marchessault, R H

    1977-01-01

    Hyphal walls of Aspergillus awamori containing increased amount of the alpha-glucan, nigeran, became correspondingly more opaque when viewed in the electron microscope as shadowed preparations. However, increased polymer deposition was not accompanied by any significant change in wall thickness. The nigeran of both A. awamori and Aspergillus niger occurred in situ in a crystalline conformation identical to that of single crystals prepared with pure polysaccharide. Furthermore, this polymer was the dominant crystalline material in the hyphae whether or not they were enriched in nigeran. Enzymic digestion of nigeran in A. niger and A. awamori revealed that the bulk of the polymer was exposed to the cell's exterior. However, a certain fraction was accessible to enzymic attack only after the wall was treated with boiling water. A third portion, detectable only by x-ray diffraction, was associated with other components and could not be extracted, even with prolonged boiling. It was removed by hot, dilute alkali and was associated in the wall with another glucan fraction. Dry heating of A. niger walls altered their susceptibility to enzymic digestion of nigeran in situ. It is proposed that this treatment introduces interstices in the crystal surface that facilitate attack. Images PMID:914782

  8. Recent advances in the understanding of the Aspergillus fumigatus cell wall.

    PubMed

    Lee, Mark J; Sheppard, Donald C

    2016-03-01

    Over the past several decades, research on the synthesis and organization of the cell wall polysaccharides of Aspergillus fumigatus has expanded our knowledge of this important fungal structure. Besides protecting the fungus from environmental stresses and maintaining structural integrity of the organism, the cell wall is also the primary site for interaction with host tissues during infection. Cell wall polysaccharides are important ligands for the recognition of fungi by the innate immune system and they can mediate potent immunomodulatory effects. The synthesis of cell wall polysaccharides is a complicated process that requires coordinated regulation of many biosynthetic and metabolic pathways. Continuous synthesis and remodeling of the polysaccharides of the cell wall is essential for the survival of the fungus during development, reproduction, colonization and invasion. As these polysaccharides are absent from the human host, these biosynthetic pathways are attractive targets for antifungal development. In this review, we present recent advances in our understanding of Aspergillus fumigatus cell wall polysaccharides, including the emerging role of cell wall polysaccharides in the host-pathogen interaction. PMID:26920883

  9. [Azole resistance in Aspergillus fumigatus in the Netherlands--increase due to environmental fungicides?].

    PubMed

    Verweij, Paul E; van de Sande-Bruisma, Nienke; Kema, Gert H J; Melchers, Willem J G

    2012-01-01

    The mould Aspergillus fumigatus may develop mechanisms that confer resistance to itraconazole, voriconazole and posaconazole. In the Netherlands a dominant resistance mechanism referred to as TR/L98H is found. In A. fumigatus isolates recovered from clinical samples in Dutch hospitals the prevalence of azole resistance varied between 0.8% and 9.4%. The TR/L98H resistance mechanism probably develops in our environment, as azoles are frequently used for crop protection and material preservation. It is likely that breathing in the resistant spores of these strains from the environment leads to clinical infection. More research is needed to understand the environmental route of resistance development and to enable effective measures to prevent this occurring. Azole resistance is associated with treatment failure. Of 8 patients with azole-resistant invasive aspergillosis 7 died within 12 weeks of diagnosis. Alternative treatment regimens might include lipid-formulation of amphotericin B or a combination of voriconazole and an echinocandin, but there is little data available to support these choices. Physicians who treat patients with Aspergillus diseases should be aware of the possibility of azole resistance, also in azole-naïve patients. PMID:22748367

  10. Proteomic Profiling of Serological Responses to Aspergillus fumigatus Antigens in Patients with Invasive Aspergillosis.

    PubMed

    Teutschbein, Janka; Simon, Svenja; Lother, Jasmin; Springer, Jan; Hortschansky, Peter; Morton, C Oliver; Löffler, Jürgen; Einsele, Hermann; Conneally, Eibhlin; Rogers, Thomas R; Guthke, Reinhard; Brakhage, Axel A; Kniemeyer, Olaf

    2016-05-01

    Aspergillus fumigatus is the species that most commonly causes the opportunistic infection invasive aspergillosis (IA) in patients being treated for hematological malignancies. Little is known about the A. fumigatus proteins that trigger the production of Aspergillus-specific IgG antibodies during the course of IA. To characterize the serological response to A. fumigatus protein antigens, mycelial proteins were separated by 2-D gel electrophoresis. The gels were immunoblotted with sera from patients with probable and proven IA and control patients without IA. We identified 49 different fungal proteins, which gave a positive IgG antibody signal. Most of these antigens play a role in primary metabolism and stress responses. Overall, our analysis identified 18 novel protein antigens from A. fumigatus. To determine whether these antigens can be used as diagnostic or prognostic markers or exhibit a protective activity, we employed supervised machine learning with decision trees. We identified two candidates for further analysis, the protein antigens CpcB and Shm2. Heterologously produced Shm2 induced a strongly proinflammatory response in human peripheral blood mononuclear cells after in vitro stimulation. In contrast, CpcB did not activate the immune response of PBMCs. These findings could serve as the basis for the development of an immunotherapy of IA. PMID:26974881

  11. Lightning Protection

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Lightning Technologies, Inc., Pittsfield, MA, - a spinoff company founded by president J. Anderson Plumer, a former NASA contractor employee who developed his expertise with General Electric Company's High Voltage Laboratory - was a key player in Langley Research Center's Storm Hazards Research Program. Lightning Technologies used its NASA acquired experience to develop protective measures for electronic systems and composite structures on aircraft, both of which are particularly susceptible to lightning damage. The company also provides protection design and verification testing services for complete aircraft systems or individual components. Most aircraft component manufacturers are among Lightning Technologies' clients.

  12. Influence of the antimicrobial compound allyl isothiocyanate against the Aspergillus parasiticus growth and its aflatoxins production in pizza crust.

    PubMed

    Quiles, Juan M; Manyes, Lara; Luciano, Fernando; Mañes, Jordi; Meca, Giuseppe

    2015-09-01

    Aflatoxins (AFs) are secondary metabolites produced by different species of Aspergillus, such as Aspergillus flavus and Aspergillus parasiticus, which possess mutagenic, teratogenic and carcinogenic activities in humans. In this study, active packaging devices containing allyl isothiocyanate (AITC) or oriental mustard flour (OMF) + water were tested to inhibit the growth of A. parasiticus and AFs production in fresh pizza crust after 30 d. The antimicrobial and anti-aflatoxin activities were compared to a control group (no antimicrobial treatment) and to a group added with commercial preservatives (sorbic acid + sodium propionate). A. parasiticus growth was only inhibited after 30 d by AITC in filter paper at 5 μL/L and 10 μL/L, AITC sachet at 5 μL/L and 10 μL/L and OMF sachet at 850 mg + 850 μL of water. However, AFs production was inhibited by all antimicrobial treatments in a dose-dependent manner. More importantly, AITC in a filter paper at 10 μL/L, AITC sachet at 10 μL/L, OMF sachet at 850 mg + 850 μL of water and sorbic acid + sodium propionate at 0.5-2.0 g/Kg completely inhibited AFs formation. The use of AITC in active packaging devices could be a natural alternative to avoid the growth of mycotoxinogenic fungi in refrigerated bakery products in substitution of common commercial preservatives. PMID:26146190

  13. Isolation of culturable mycobiota from agricultural soils and determination of tolerance to glyphosate of nontoxigenic Aspergillus section Flavi strains.

    PubMed

    Carranza, Cecilia S; Barberis, Carla L; Chiacchiera, Stella M; Dalcero, Ana María; Magnoli, Carina E

    2016-01-01

    Glyphosate-based herbicides are extensively used in Argentina's agricultural system to control undesirable weeds. This study was conducted to evaluate the culturable mycobiota [colony forming units (CFU) g(-1) and frequency of fungal genera or species] from an agricultural field exposed to pesticides. In addition, we evaluated the tolerance of A. oryzae and nontoxigenic A. flavus strains to high concentrations (100 to 500 mM - 17,000 to 84,500 ppm) of a glyphosate commercial formulation. The analysis of the mycobiota showed that the frequency of the main fungal genera varied according to the analyzed sampling period. Aspergillus spp. or Aspergillus section Flavi strains were isolated from 20 to 100% of the soil samples. Sterilia spp. were also observed throughout the sampling (50 to 100%). Aspergillus section Flavi tolerance assays showed that all of the tested strains were able to develop at the highest glyphosate concentration tested regardless of the water availability conditions. In general, significant reductions in growth rates were observed with increasing concentrations of the herbicide. However, a complete inhibition of fungal growth was not observed with the concentrations assayed. This study contributes to the knowledge of culturable mycobiota from agricultural soils exposed to pesticides and provides evidence on the effective growth ability of A. oryzae and nontoxigenic A. flavus strains exposed to high glyphosate concentrations in vitro. PMID:26549415

  14. New Insight into the Ochratoxin A Biosynthetic Pathway through Deletion of a Nonribosomal Peptide Synthetase Gene in Aspergillus carbonarius

    SciTech Connect

    Gallo, A.; Bruno, K. S.; Solfrizzo, M.; Perrone, G.; Mule, G.; Visconti, A.; Baker, S. E.

    2012-09-14

    Ochratoxin A (OTA), a mycotoxin produced by Aspergillus and Penicillium species, is composed of a dihydroisocoumarin ring linked to phenylalanine and its biosynthetic pathway has not yet been completely elucidated. Most of the knowledge regarding the genetic and enzymatic aspects of OTA biosynthesis has been obtained in Penicillium species. In Aspergillus species only pks genes involved in the initial steps of the pathway have been partially characterized. In our study, the inactivation of a gene encoding a nonribosomal peptide synthetase in OTA producing A. carbonarius ITEM 5010 has removed the ability of the fungus to produce OTA. This is the first report on the involvement of an nrps gene product in OTA biosynthetic pathway in Aspergillus species. The absence of OTA and ochratoxin α-the isocoumaric derivative of OTA, and the concomitant increase of ochratoxin β- the dechloro analog of ochratoxin α- were observed in the liquid culture of transformed strain. The data provide the first evidence that the enzymatic step adding phenylalanine to polyketide dihydroisocoumarin precedes the chlorination step to form OTA in A. carbonarius, and that ochratoxin α is a product of hydrolysis of OTA, giving an interesting new insight in the biosynthetic pathway of the toxin.

  15. Acute community acquired Aspergillus pneumonia in a presumed immunocompetent host

    PubMed Central

    Sridhar, Varun; Rajagopalan, Natarajan; C, Shivaprasad; Patil, Mahantesh; Varghese, Jaicob

    2012-01-01

    Infection from Aspergillus results in a wide range of diseases from simple Aspergillus pneumonia to fatal invasive Aspergillosis. Though the fungus is known to predominantly affect the immunocompromised host, it has also been known to cause acute pneumonia in immunocompetent hosts which is invariably fatal. It presents as an acute pneumonia with bilateral chest infiltrates on radiograph. Early clinical suspicion and microbiological identification by measures such as broncho alveolar lavage and initiation of therapy with voricanozole significantly increase the chances of survival. In this article the authors discuss a case of acute community acquired Aspergillus pneumonia in an immunocompetent host who survived due to early identification and prompt treatment with appropriate antifungal medication. PMID:22605848

  16. Biosorption potency of Aspergillus niger for removal of chromium (VI).

    PubMed

    Srivastava, Shaili; Thakur, Indu Shekhar

    2006-09-01

    Aspergillus niger isolated from soil and effluent of leather tanning mills had higher activity to remove chromium. The potency of Aspergillus niger was evaluated in shake flask culture by absorption of chromium at pH 6 and temperature 30 degrees C. The results of the study indicated removal of more than 75% chromium by Aspergillus niger determined by diphenylcarbazide colorimetric assay and atomic absorption spectrophotometry after 7 days. Study of microbial Cr(VI) reduction and identification of reduction intermediates has been hindered by the lack of analytical techniques that can identify the oxidation state with subcellular spatial resolution. Therefore, removal of chromium was further substantiated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX), which indicated an accumulation of chromium in the fungal mycelium. PMID:16874547

  17. Heterologous expression of Aspergillus terreus fructosyltransferase in Kluyveromyces lactis.

    PubMed

    Spohner, Sebastian C; Czermak, Peter

    2016-06-25

    Fructo-oligosaccharides are prebiotic and hypocaloric sweeteners that are usually extracted from chicory. They can also be produced from sucrose using fructosyltransferases, but the only commercial enzyme suitable for this purpose is Pectinex Ultra, which is produced with Aspergillus aculeatus. Here we used the yeast Kluyveromyces lactis to express a secreted recombinant fructosyltransferase from the inulin-producing fungus Aspergillus terreus. A synthetic codon-optimised version of the putative β-fructofuranosidase ATEG 04996 (XP 001214174.1) from A. terreus NIH2624 was secreted as a functional protein into the extracellular medium. At 60°C, the purified A. terreus enzyme generated the same pattern of oligosaccharides as Pectinex Ultra, but at lower temperatures it also produced oligomers with up to seven units. We achieved activities of up to 986.4U/mL in high-level expression experiments, which is better than previous reports of optimised Aspergillus spp. fermentations. PMID:27084521

  18. [Utility of Aspergillus-LFD: first experience in Chile].

    PubMed

    Alvarez, Eduardo

    2015-02-01

    The diagnosis of invasive aspergillosis remains a challenge. Detection of galactomannan in serum and bronchoalveolar lavage is a useful tool; however due to methodological and economic reasons, the test frequencies of galactomannan assays vary from daily to weekly, which constitute a risk to the patient. In this study, we aimed to evaluate and correlate the performance of the new kit Aspergillus-LFD with the GM-EIA. Aspergillus-LFD kit represents a fast, economical and simple test; showed a good performance and excellent correlation with GM-EIA kit. Given the above, the Aspergillus-LFD is emerging as an alternative to consider in the early diagnosis of invasive aspergillosis. PMID:25860056

  19. Role of prostaglandin D2 /CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus.

    PubMed

    Liu, Haixia; Zheng, Mingrui; Qiao, Jianou; Dang, Yajie; Zhang, Pengyu; Jin, Xianqiao

    2014-05-01

    Aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not been fully understood. Here, we evaluated the immunological mechanisms and the role of the prostaglandin D2 / Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus-associated asthma exacerbation. We studied the effects of A. fumigatus on airway inflammation and bronchial hyper-responsiveness in a rat model of chronic asthma. Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and bronchial hyper-responsiveness in ovalbumin-sensitized, challenged rats. These changes were associated with prostaglandin D2 synthesis and CRTH2 expression in the lungs. Direct inflammation occurred in ovalbumin-sensitized, challenged animals, whereas pre-treatment with an antagonist against CRTH2 nearly completely eliminated the A. fumigatus-induced worsening of airway eosinophilia and bronchial hyper-responsiveness. Our data demonstrate that production of prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenic factors responsible for the A. fumigatus-induced enhancement of airway inflammation and responsiveness. PMID:24329550

  20. Heterologous, Expression, and Characterization of Thermostable Glucoamylase Derived from Aspergillus flavus NSH9 in Pichia pastoris

    PubMed Central

    Karim, Kazi Muhammad Rezaul; Hossain, Md. Anowar; Sing, Ngieng Ngui; Mohd Sinang, Fazia; Hussain, Mohd Hasnain Md.; Roslan, Hairul Azman

    2016-01-01

    A novel thermostable glucoamylase cDNA without starch binding domain (SBD) of Aspergillus flavus NSH9 was successfully identified, isolated, and overexpressed in Pichia pastoris GS115. The complete open reading frame of glucoamylase from Aspergillus flavus NSH9 was identified by employing PCR that encodes 493 amino acids lacking in the SBD. The first 17 amino acids were presumed to be a signal peptide. The cDNA was cloned into Pichia pastoris and the highest expression of recombinant glucoamylase (rGA) was observed after 8 days of incubation period with 1% methanol. The molecular weight of the purified rGA was about 78 kDa and exhibited optimum catalytic activity at pH 5.0 and temperature of 70°C. The enzyme was stable at higher temperature with 50% of residual activity observed after 20 min at 90°C and 100°C. Low concentration of metal (Mg++, Fe++, Zn++, Cu++, and Pb++) had positive effect on rGA activity. This rGA has the potential for use and application in the saccharification steps, due to its thermostability, in the starch processing industries. PMID:27504454

  1. Effect of Carum copticum essential oil on growth and aflatoxin formation by Aspergillus strains.

    PubMed

    Kazemi, M

    2015-01-01

    The objectives of this study were to determine the antiaflatoxin B1 activity in vitro of the essential oil (EO) extracted from the seeds of Carum copticum and to evaluate its antifungal activity in vivo as a potential food preservative. The C. copticum EO exhibited noticeable inhibition on dry mycelium and synthesis of aflatoxin B1 (AFB1) by Aspergillus flavus, completely inhibiting AFB1 production at 4 μL/mL. C. copticum EOs showed the lowest percentages of decayed cherry tomatoes for all fungi compared with the control at 100 μL/mL with values of 5.01 ± 67% for A. flavus and 5.98 ± 54% for Aspergillus niger. The results indicated that the percentage of infected fruits is significantly (p < 0.01) reduced by the EO at 16°C for 30 days. In this case, the oil at 100 μL/mL concentration showed the highest inhibition of fungal infection with a value of 80.45% compared with the control. Thus, the EO of dill could be used to control food spoilage and as a potential source of food preservative. PMID:25342249

  2. Scientific Advances with Aspergillus Species that Are Used for Food and Biotech Applications.

    PubMed

    Biesebeke, Rob Te; Record, Erik

    2008-01-01

    Yeast and filamentous fungi have been used for centuries in diverse biotechnological processes. Fungal fermentation technology is traditionally used in relation to food production, such as for bread, beer, cheese, sake and soy sauce. Last century, the industrial application of yeast and filamentous fungi expanded rapidly, with excellent examples such as purified enzymes and secondary metabolites (e.g. antibiotics), which are used in a wide range of food as well as non-food industries. Research on protein and/or metabolite secretion by fungal species has focused on identifying bottlenecks in (post-) transcriptional regulation of protein production, metabolic rerouting, morphology and the transit of proteins through the secretion pathway. In past years, genome sequencing of some fungi (e.g. Aspergillus oryzae, Aspergillus niger) has been completed. The available genome sequences have enabled identification of genes and functionally important regions of the genome. This has directed research to focus on a post-genomics era in which transcriptomics, proteomics and metabolomics methodologies will help to explore the scientific relevance and industrial application of fungal genome sequences. PMID:21558706

  3. Heterologous, Expression, and Characterization of Thermostable Glucoamylase Derived from Aspergillus flavus NSH9 in Pichia pastoris.

    PubMed

    Karim, Kazi Muhammad Rezaul; Husaini, Ahmad; Hossain, Md Anowar; Sing, Ngieng Ngui; Mohd Sinang, Fazia; Hussain, Mohd Hasnain Md; Roslan, Hairul Azman

    2016-01-01

    A novel thermostable glucoamylase cDNA without starch binding domain (SBD) of Aspergillus flavus NSH9 was successfully identified, isolated, and overexpressed in Pichia pastoris GS115. The complete open reading frame of glucoamylase from Aspergillus flavus NSH9 was identified by employing PCR that encodes 493 amino acids lacking in the SBD. The first 17 amino acids were presumed to be a signal peptide. The cDNA was cloned into Pichia pastoris and the highest expression of recombinant glucoamylase (rGA) was observed after 8 days of incubation period with 1% methanol. The molecular weight of the purified rGA was about 78 kDa and exhibited optimum catalytic activity at pH 5.0 and temperature of 70°C. The enzyme was stable at higher temperature with 50% of residual activity observed after 20 min at 90°C and 100°C. Low concentration of metal (Mg(++), Fe(++), Zn(++), Cu(++), and Pb(++)) had positive effect on rGA activity. This rGA has the potential for use and application in the saccharification steps, due to its thermostability, in the starch processing industries. PMID:27504454

  4. Role of prostaglandin D2/CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus

    PubMed Central

    Liu, Haixia; Zheng, Mingrui; Qiao, Jianou; Dang, Yajie; Zhang, Pengyu; Jin, Xianqiao

    2014-01-01

    Aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not been fully understood. Here, we evaluated the immunological mechanisms and the role of the prostaglandin D2/ Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus-associated asthma exacerbation. We studied the effects of A. fumigatus on airway inflammation and bronchial hyper-responsiveness in a rat model of chronic asthma. Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and bronchial hyper-responsiveness in ovalbumin-sensitized, challenged rats. These changes were associated with prostaglandin D2 synthesis and CRTH2 expression in the lungs. Direct inflammation occurred in ovalbumin-sensitized, challenged animals, whereas pre-treatment with an antagonist against CRTH2 nearly completely eliminated the A. fumigatus-induced worsening of airway eosinophilia and bronchial hyper-responsiveness. Our data demonstrate that production of prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenic factors responsible for the A. fumigatus-induced enhancement of airway inflammation and responsiveness. PMID:24329550

  5. Biodiversity of Aspergillus species in some important agricultural products

    PubMed Central

    Perrone, G.; Susca, A.; Cozzi, G.; Ehrlich, K.; Varga, J.; Frisvad, J.C.; Meijer, M.; Noonim, P.; Mahakarnchanakul, W.; Samson, R.A.

    2007-01-01

    The genus Aspergillus is one of the most important filamentous fungal genera. Aspergillus species are used in the fermentation industry, but they are also responsible of various plant and food secondary rot, with the consequence of possible accumulation of mycotoxins. The aflatoxin producing A. flavus and A. parasiticus, and ochratoxinogenic A. niger, A. ochraceus and A. carbonarius species are frequently encountered in agricultural products. Studies on the biodiversity of toxigenic Aspergillus species is useful to clarify molecular, ecological and biochemical characteristics of the different species in relation to their different adaptation to environmental and geographical conditions, and to their potential toxigenicity. Here we analyzed the biodiversity of ochratoxin producing species occurring on two important crops: grapes and coffee, and the genetic diversity of A. flavus populations occurring in agricultural fields. Altogether nine different black Aspergillus species can be found on grapes which are often difficult to identify with classical methods. The polyphasic approach used in our studies led to the identification of three new species occurring on grapes: A. brasiliensis, A. ibericus, and A. uvarum. Similar studies on the Aspergillus species occurring on coffee beans have evidenced in the last five years that A. carbonarius is an important source of ochratoxin A in coffee. Four new species within the black aspergilli were also identified in coffee beans: A. sclerotioniger, A. lacticoffeatus, A. sclerotiicarbonarius, and A. aculeatinus. The genetic diversity within A. flavus populations has been widely studied in relation to their potential aflatoxigenicity and morphological variants L- and S-strains. Within A. flavus and other Aspergillus species capable of aflatoxin production, considerable diversity is found. We summarise the main recent achievements in the diversity of the aflatoxin gene cluster in A. flavus populations, A. parasiticus and the non

  6. Concurrent sensitization to Aspergillus Fumigatus in tropical pulmonary eosinophilia.

    PubMed

    Chhabra, Sunil K; Dash, Devi Jyoti

    2016-01-01

    Tropical pulmonary eosinophilia (TPE) is characterized by lung tissue and peripheral blood eosinophilia. Serum total IgE is also markedly increased in TPE. However, an association with asthma or other hypersensitivity conditions has not been described. During the diagnostic workup of three patients eventually confirmed to have TPE, hypersensitivity to the fungus, Aspergillus Fumigatus was found. However, there was no evidence of diseases of aspergillus hypersensitivity such as severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA). This association however raises the possibility of a future risk of these potentially serious allergic respiratory manifestations. PMID:27374215

  7. Aspergillus genomes: secret sex and the secrets of sex.

    PubMed

    Scazzocchio, Claudio

    2006-10-01

    The genomic sequences of three species of Aspergillus, including the model organism A. nidulans (which is homothallic: having no differentiated mating types, a strain being able to cross with itself), suggest that A. fumigatus and A. oryzae, considered to be asexual, might in fact be heterothallic (having two differentiated mating types, a strain being able to cross only with strains of opposite mating type). The genomic data have implications for the understanding of the evolution and the mechanism of sexual reproduction in this genus. We propose a model of epigenetic heterothallism to account for the reproductive patterns observed in Aspergillus nidulans. PMID:16911845

  8. Polyphasic taxonomy of Aspergillus section Fumigati and its teleomorph Neosartorya

    PubMed Central

    Samson, R.A.; Hong, S.; Peterson, S.W.; Frisvad, J.C.; Varga, J.

    2007-01-01

    The taxonomy of Aspergillus section Fumigati with its teleomorph genus Neosartorya is revised. The species concept is based on phenotypic (morphology and extrolite profiles) and molecular (β-tubulin and calmodulin gene sequences) characters in a polyphasic approach. Four new taxa are proposed: N. australensis N. ferenczii, N. papuaensis and N. warcupii. All newly described and accepted species are illustrated. The section consists of 33 taxa: 10 strictly anamorphic Aspergillus species and 23 Neosartorya species. Four other Neosartorya species described previously were not available for this monograph, and consequently are relegated to the category of doubtful species. PMID:18490953

  9. Intracranial mycotic aneurysm caused by Aspergillus--case report.

    PubMed

    Masago, A; Fukuoka, H; Yoshida, T; Majima, K; Tada, T; Nagai, H

    1992-11-01

    A 75-year-old female with chronic renal failure diagnosed as Wegener's granulomatosis was receiving steroids and immunosuppressive agents when subarachnoid hemorrhage developed. Cerebral angiography showed a fusiform aneurysm arising from an angular branch of the left middle cerebral artery. Hemorrhage occurred and the aneurysm was excised by emergency surgery. Microscopic examination of the aneurysm revealed dense infiltration of hyphae identified as Aspergillus. She died of subsequent hemorrhage. Autopsy showed numerous Aspergillus hyphae in the lung. Fungal mycotic aneurysm should be considered in the differential diagnosis of an immunocompromised patient with subarachnoid hemorrhage. PMID:1282683

  10. Identification of Glucose Transporters in Aspergillus nidulans

    PubMed Central

    dos Reis, Thaila Fernanda; Menino, João Filipe; Bom, Vinícius Leite Pedro; Brown, Neil Andrew; Colabardini, Ana Cristina; Savoldi, Marcela; Goldman, Maria Helena S.; Rodrigues, Fernando; Goldman, Gustavo Henrique

    2013-01-01

    To characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose. PMID:24282591