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

      review-article
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      Frontiers in Microbiology
      Frontiers Media S.A.
      Aspergillus, gliotoxin, fumagillin, extrolites, proxy-exometabolites

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          Abstract

          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.

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          Most cited references206

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          Aspergillus fumigatus and aspergillosis.

          J P Latgé (1999)
          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.
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            Regulation of fungal secondary metabolism.

            Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.
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              Surface hydrophobin prevents immune recognition of airborne fungal spores.

              The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many antigens and allergens, it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (DeltarodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                07 January 2016
                2015
                : 6
                : 1485
                Affiliations
                Section of Eukaryotic Biotechnology, Department of Systems Biology, Technical University of Denmark Kongens Lyngby, Denmark
                Author notes

                Edited by: Frederic Lamoth, Lausanne University Hospital, Switzerland

                Reviewed by: Vito Valiante, Leibniz-Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Germany; William Charles Nierman, J. Craig Venter Institute, USA; Miroslav Kolarik Kolarik, Institute of Microbiology, Czech Republic

                *Correspondence: Jens C. Frisvad jcf@ 123456bio.dtu.dk

                This article was submitted to Fungi and Their Interactions, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2015.01485
                4703822
                26779142
                fe02da2a-6698-4032-957f-83ec7e49251f
                Copyright © 2016 Frisvad and Larsen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 August 2015
                : 09 December 2015
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 236, Pages: 14, Words: 12663
                Funding
                Funded by: Agilent Technologies 10.13039/501100002709
                Award ID: 2871
                Funded by: Novo Nordisk 10.13039/501100004191
                Award ID: 13OC0005201
                Categories
                Microbiology
                Mini Review

                Microbiology & Virology
                aspergillus,gliotoxin,fumagillin,extrolites,proxy-exometabolites
                Microbiology & Virology
                aspergillus, gliotoxin, fumagillin, extrolites, proxy-exometabolites

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