title: Comparison of susceptibility and transcription profile of the new antifungal hassallidin A with caspofungin.
abstract: This is the first report on the antifungal effects of the new glycolipopeptide hassallidin A. Due to related molecular structure moieties between hassallidin A and the established antifungal drug caspofungin we assumed parallels in the effects on cell viability. Therefore we compared hassallidin A with caspofungin by antifungal susceptibility testing and by analysing the genome-wide transcriptional profile of Candida albicans. Furthermore, we examined modifications in ultracellular structure due to hassallidin A treatment by electron microscopy. Hassallidin A was found to be fungicidal against all tested Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8 microg/ml, independently from the species. Electron microscopy revealed noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A. Comparing the transcriptional profile of C. albicans cells treated with hassallidin A to that of cells exposed to caspofungin, only 20 genes were found to be similarly up- or down-regulated in both assays, while 227 genes were up- or down-regulated induced by hassallidin A specifically. Genes up-regulated in cells exposed to hassallidin A included metabolic and mitotic genes, while genes involved in DNA repair, vesicle docking, and membrane fusion were down-regulated. In summary, our data suggest that, although hassallidin A and caspofungin have similar structures, however, the effects on susceptibility and transcriptional response to yeasts seem to be different.
authors.affiliation: Technische Universität Berlin, Institut für Chemie, FG Biochemie und Molekulare Biologie, 10587 Berlin, Germany. t.neuhof@gmx.de
authors.forename: Torsten
authors.initials: T
authors.lastname: Neuhof
authors.forename: Michael
authors.initials: M
authors.lastname: Seibold
authors.forename: Sascha
authors.initials: S
authors.lastname: Thewes
authors.forename: Michael
authors.initials: M
authors.lastname: Laue
authors.forename: Chang-Ok
authors.initials: CO
authors.lastname: Han
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
authors.forename: Hans
authors.initials: H
authors.lastname: von Döhren
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D000077336:Caspofungin; D003455:Cryptococcus neoformans / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D054714:Echinocandins; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006017:Glycolipids / Q000494:pharmacology*; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D006017:Glycolipids; D055666:Lipopeptides; D008074:Lipoproteins; D010455:Peptides; D010456:Peptides, Cyclic; C501712:hassallidin A; D000077336:Caspofungin