title: Synergistic activity of the tyrocidines, antimicrobial cyclodecapeptides from Bacillus aneurinolyticus, with amphotericin B and caspofungin against Candida albicans biofilms.
abstract: Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus that are characterized by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonic Candida albicans in the low-micromolar range. These tyrocidines also prevented C. albicans biofilm formation in vitro. Studies with the membrane-impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of mature C. albicans biofilm cells. This membrane activity correlated with the permeabilization and rapid lysis of model fungal membranes containing phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in combination with two key antifungal drugs, amphotericin B and caspofungin. Using a Caenorhabditis elegans infection model, we found that tyrocidine A potentiated the activity of caspofungin. Therefore, tyrocidines are promising candidates for further research as antifungal drugs and as agents for combinatorial treatment.
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, Science Faculty, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: Anscha Mari
authors.initials: AM
authors.lastname: Troskie
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, Science Faculty, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: Marina
authors.initials: M
authors.lastname: Rautenbach
authors.affiliation: Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Heverlee, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delattin
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, Science Faculty, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: Johan Arnold
authors.initials: JA
authors.lastname: Vosloo
authors.affiliation: Leibniz Institute of Molecular Pharmacology, Berlin, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Dathe
authors.affiliation: Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Heverlee, Belgium Department of Plant Systems Biology, VIB, Ghent, Belgium bruno.cammue@biw.kuleuven.be.
authors.forename: Bruno P A
authors.initials: BP
authors.lastname: Cammue
authors.affiliation: Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Heverlee, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001407:Bacillus / Q000737:chemistry*; D018441:Biofilms / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000382:microbiology; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D000077336:Caspofungin; D002463:Cell Membrane Permeability; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology*; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014440:Tyrocidine / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D017382:Reactive Oxygen Species; D014440:Tyrocidine; D000666:Amphotericin B; D000077336:Caspofungin
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