title: Acyclic sesquiterpenes released by Candida albicans inhibit growth of dermatophytes.
abstract: It is unresolved as to whether fungi that share a common skin habitat might in principal interact. In in vitro screening tests with Candida albicans, Trichophytum rubrum and other common dermatophytes, we found C. albicans releases volatile compounds that inhibit growth of the dermatophytes. By applying (enantioselective) gas chromatography combined with mass spectrometry we identified 8 compounds among which stereochemically pure (3R,6E)-2,3-dihydrofarnesol (R-DHF) and (2E,6E)-farnesol (F-ol) were the main components. Synthetic R-DHF and its enantiomer, (3S,6E)-2,3-dihydrofarnesol (S-DHF), as well as F-ol were tested for their capacity to inhibit growth of dermatophytes in microtiter-plate assays over 62 h. All three compounds showed significant and concentration-dependent, to a certain extent even species-specific, inhibitory effects on T. rubrum, T. mentagrophytes, Microsporum canis and Epidermophyton floccosum. In general, S-DHF and F-ol had a pronounced effect on the dermatophytes, similar to or even stronger than that of fluconazole. E. floccosum was completely suppressed by 12.5 μg/ml dihydrofarnesol, as was the inhibition caused by 50 μg/ml fluconazole. Similarly, S-DHF- was more active against T. rubrum than fluconazole. To the best of our knowledge, 2,3-dihydrofarnesol has not yet been described as a volatile generated by microorganisms, and its inhibitory effect on dermatophytes is new to science. However, the relevance of this compound in interfungal interference in situ is unknown. In contrast, farnesol is a well-known semiochemical of C. albicans with intraspecific effects and a clear impact on other microorganisms. Mutual intermicrobial communication based on fungal volatiles therefore appears to be an exciting field for future investigations.
authors.affiliation: Department of Dermatology, University Hospitals of Schleswig-Holstein, Kiel.
authors.forename: Jochen
authors.initials: J
authors.lastname: Brasch
authors.forename: Felix
authors.initials: F
authors.lastname: Horter
authors.forename: Daniel
authors.initials: D
authors.lastname: Fritsch
authors.forename: Vera
authors.initials: V
authors.lastname: Beck-Jendroschek
authors.forename: Armin
authors.initials: A
authors.lastname: Tröger
authors.forename: Wittko
authors.initials: W
authors.lastname: Francke
mesh_terms: D000898:Antibiosis; D000935:Antifungal Agents / Q000378:metabolism*; D003883:Arthrodermataceae / Q000187:drug effects* / Q000254:growth & development*; D002176:Candida albicans / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008826:Microbial Sensitivity Tests; D012717:Sesquiterpenes / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D012717:Sesquiterpenes
keywords: Fungi; antifungals; dihydrofarnesol; enantiomers; farnesol; semiochemicals