Acyclic sesquiterpenes released byCandida albicansinhibit 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.

Bacterioruberin extracts from a genetically modified hyperpigmented Haloferax volcanii strain: antioxidant activity and bioactive properties on sperm cells

“…On the other hand, 2,3,dihydrofarnesol (R‐DHF) and its isomers inhibited the growth of Dermatophytes, causal agents of human skin infections (Brasch et al . ). This means that the HVLON3 extract contains other bioactive compounds, in addition to Bctr, with beneficial effects to human health.…”

“…2,3, dihydrofarnesol is produced by plants as a volatile compound of flowers (Brasch et al . ) and it is used as a pheromone in male bees (Brabcová et al . ).…”

“…However, it is interesting to note that these authors observed that sesquiterpenic compounds (including trans, trans-farnesol) show cytotoxic and antiproliferative activity in vitro against cancer cell lines. On the other hand, 2,3,dihydrofarnesol (R-DHF) and its isomers inhibited the growth of Dermatophytes, causal agents of human skin infections (Brasch et al 2013). This means that the HVLON3 extract contains other bioactive compounds, in addition to Bctr, with beneficial effects to human health.…”

“…This means that the HVLON3 extract contains other bioactive compounds, in addition to Bctr, with beneficial effects to human health. 2,3, dihydrofarnesol is produced by plants as a volatile compound of flowers (Brasch et al 2013) and it is used as a pheromone in male bees (Brabcov a et al 2015). In Candida albicans, farnesol is involved in quorum sensing signalling (Padder et al 2018), however, its biological relevance in microorganisms is scarcely known.…”

Noisy neighbourhoods: quorum sensing in fungal-polymicrobial infections

“…Farnesol and other related alcohols produced by C . albicans can also inhibit the growth of dermatophytes (Brasch et al ., ), which cause superficial skin and nail infections, including ringworm and athlete's foot (Soll, ). Importantly, at high concentrations, farnesol induces apoptosis in Candida species (Shirtliff et al ., ), suggesting that farnesol can not only be used to gain a competitive advantage but also as a measure to restrict growth.…”