title: Fungi treated with small chemicals exhibit increased antimicrobial activity against facultative bacterial and yeast pathogens.
abstract: For decades, fungi have been the main source for the discovery of novel antimicrobial drugs. Recent sequencing efforts revealed a still high number of so far unknown "cryptic" secondary metabolites. The production of these metabolites is presumably epigenetically silenced under standard laboratory conditions. In this study, we investigated the effect of six small mass chemicals, of which some are known to act as epigenetic modulators, on the production of antimicrobial compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples was tested against clinically facultative pathogens and multiresistant clinical isolates. In total, 30 samples of treated fungi belonging to six different genera reduced significantly growth of different test organisms compared to the untreated fungal sample (growth log reduction 0.3-4.3). For instance, the pellet of Penicillium restrictum grown in the presence of butyrate revealed significant higher antimicrobial activity against Staphylococcus (S.) aureus and multiresistant S. aureus strains and displayed no cytotoxicity against human cells, thus making it an ideal candidate for antimicrobial compound discovery. Our study shows that every presumable fungus, even well described fungi, has the potential to produce novel antimicrobial compounds and that our approach is capable of rapidly filling the pipeline for yet undiscovered antimicrobial substances.
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zutz
authors.affiliation: AIT-Austrian Institute of Technology GmbH, University and Research Campus Tulln, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria.
authors.forename: Dragana
authors.initials: D
authors.lastname: Bandian
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria ; Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, BOKU University of Natural Resources and Life Sciences Vienna, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Neumayer
authors.affiliation: Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, BOKU University of Natural Resources and Life Sciences Vienna, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Speringer
authors.affiliation: AIT-Austrian Institute of Technology GmbH, University and Research Campus Tulln, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria ; Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, BOKU University of Natural Resources and Life Sciences Vienna, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria.
authors.forename: Markus
authors.identifier: 0000-0003-3010-6044
authors.initials: M
authors.lastname: Gorfer
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Wagner
authors.affiliation: AIT-Austrian Institute of Technology GmbH, University and Research Campus Tulln, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria ; Fungal Genetics and Genomics Unit, Department of Applied Genetics and Cell Biology, BOKU University of Natural Resources and Life Sciences Vienna, Konrad Lorenz Straße 24, 3430 Tulln on the Danube, Austria.
authors.forename: Joseph
authors.initials: J
authors.lastname: Strauss
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria.
authors.forename: Kathrin
authors.identifier: 0000-0001-6147-577X
authors.initials: K
authors.lastname: Rychli
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D005658:Fungi / Q000187:drug effects / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013172:Spores, Fungal / Q000187:drug effects; D015003:Yeasts / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D054852:Small Molecule Libraries; D000117:Acetylglucosamine