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      Sloth Hair as a Novel Source of Fungi with Potent Anti-Parasitic, Anti-Cancer and Anti-Bacterial Bioactivity

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          Abstract

          The extraordinary biological diversity of tropical forests harbors a rich chemical diversity with enormous potential as a source of novel bioactive compounds. Of particular interest are new environments for microbial discovery. Sloths – arboreal mammals commonly found in the lowland forests of Panama – carry a wide variety of micro- and macro-organisms on their coarse outer hair. Here we report for the first time the isolation of diverse and bioactive strains of fungi from sloth hair, and their taxonomic placement. Eighty-four isolates of fungi were obtained in culture from the surface of hair that was collected from living three-toed sloths ( Bradypus variegatus, Bradypodidae) in Soberanía National Park, Republic of Panama. Phylogenetic analyses revealed a diverse group of Ascomycota belonging to 28 distinct operational taxonomic units (OTUs), several of which are divergent from previously known taxa. Seventy-four isolates were cultivated in liquid broth and crude extracts were tested for bioactivity in vitro. We found a broad range of activities against strains of the parasites that cause malaria ( Plasmodium falciparum) and Chagas disease ( Trypanosoma cruzi), and against the human breast cancer cell line MCF-7. Fifty fungal extracts were tested for antibacterial activity in a new antibiotic profile screen called BioMAP; of these, 20 were active against at least one bacterial strain, and one had an unusual pattern of bioactivity against Gram-negative bacteria that suggests a potentially new mode of action. Together our results reveal the importance of exploring novel environments for bioactive fungi, and demonstrate for the first time the taxonomic composition and bioactivity of fungi from sloth hair.

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          Diversity and host range of foliar fungal endophytes: are tropical leaves biodiversity hotspots?

          Fungal endophytes are found in asymptomatic photosynthetic tissues of all major lineages of land plants. The ubiquity of these cryptic symbionts is clear, but the scale of their diversity, host range, and geographic distributions are unknown. To explore the putative hyperdiversity of tropical leaf endophytes, we compared endophyte communities along a broad latitudinal gradient from the Canadian arctic to the lowland tropical forest of central Panama. Here, we use molecular sequence data from 1403 endophyte strains to show that endophytes increase in incidence, diversity, and host breadth from arctic to tropical sites. Endophyte communities from higher latitudes are characterized by relatively few species from many different classes of Ascomycota, whereas tropical endophyte assemblages are dominated by a small number of classes with a very large number of endophytic species. The most easily cultivated endophytes from tropical plants have wide host ranges, but communities are dominated by a large number of rare species whose host range is unclear. Even when only the most easily cultured species are considered, leaves of tropical trees represent hotspots of fungal species diversity, containing numerous species not yet recovered from other biomes. The challenge remains to recover and identify those elusive and rarely cultured taxa with narrower host ranges, and to elucidate the ecological roles of these little-known symbionts in tropical forests.
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            Fungal endophytes: unique plant inhabitants with great promises.

            Fungal endophytes residing in the internal tissues of living plants occur in almost every plant on earth from the arctic to the tropics. The endophyte-host relationship is described as a balanced symbiotic continuum ranging from mutualism through commensalism to parasitism. This overview will highlight selected aspects of endophyte diversity, host specificity, endophyte-host interaction and communication as well as regulation of secondary metabolite production with emphasis on advanced genomic methods and their role in improving our current knowledge of endophytic associations. Furthermore, the chemical potential of endophytic fungi for drug discovery will be discussed with focus on the detection of pharmaceutically valuable plant constituents as products of fungal biosynthesis. In addition, selected examples of bioactive metabolites reported in recent years (2008-2010) from fungal endophytes residing in terrestrial plants are presented grouped according to their reported biological activities.
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              Natural products to drugs: natural product-derived compounds in clinical trials.

              Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural product-derived compounds for which clinical trials have been halted or discontinued since 2005. Also discussed are natural product-derived drugs launched since 2005, new natural product templates and late-stage development candidates.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                15 January 2014
                : 9
                : 1
                : e84549
                Affiliations
                [1 ]Smithsonian Tropical Research Institute, Panama, Republic of Panama
                [2 ]Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, United States of America
                [3 ]Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Panama, Republic of Panama
                [4 ]School of Plant Sciences, University of Arizona, Tucson, Arizona, United States of America
                Louisiana State University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SH AEA CS WRW RL. Performed the experiments: SH AEA CS WRW RL LI. Analyzed the data: SH AEA WRW RL LI. Contributed reagents/materials/analysis tools: SH AEA WRW RL CS LI. Wrote the paper: SH AEA CS WRW RL.

                Article
                PONE-D-13-31499
                10.1371/journal.pone.0084549
                3893167
                24454729
                0966fa6a-9630-440e-9180-39ae1f9f614b
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 July 2013
                : 15 November 2013
                Page count
                Pages: 10
                Funding
                This work was supported by the International Cooperative Biodiversity Groups program (ICBG-Panama http://www.icbg.org/, grant number 2 U01 TW006634-06) and the College of Agriculture and Life Sciences at the University of Arizona. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Drug Discovery
                Biotechnology
                Drug Discovery
                Ecology
                Ecological Environments
                Terrestrial Environments
                Biodiversity
                Chemical Ecology
                Microbial Ecology
                Evolutionary Biology
                Evolutionary Systematics
                Phylogenetics
                Microbiology
                Mycology
                Fungi
                Applied Microbiology
                Microbial Control
                Medicine
                Drugs and Devices
                Drug Research and Development
                Drug Discovery

                Uncategorized
                Uncategorized

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