engleski

Isolation and cytotoxicity of low-molecular-weight metabolites of Candida albicans

In this study, the low molecular weight lypophilic metabolites of C.albicans and C. dubliniensis strains produced in a synthetic medium with the addition of fetal calf serum were identified using LC/MS and MS/MS technique and quantified. All strains investigated produce a metabolite with a UV spectra maximum at 224 and 279 nm and minimum at 243 nm. Following comparison with ESI, MS/MS spectral data of a reference compound, the metabolite was identified as 3-indoleethanol (tryptophol). The concentration of extracellular tryptophol in the biosynthesis of C. albicans and C. dubliniensis ranged from 2.45 μ g/mL to 191 μ g/mL, respectively. Contrary to previously published data, gliotoxin or gliotoxin-like compounds were not detected, and all investigated C. albicans and C. dubliniensis strains have the same metabolite profile. Cytotoxic effects of tryptophol and 3- indolelactic acid (precursor of tryptophol biosynthesis) were cell-line-dependent. The EC50 of tryptophol ranged between 2 and 7 mM, with the EC50 of 3-indolelactic acid approximately double (between 4 and 8 mM). Tryptophol exhibited cell-type dependent cytotoxicity in relatively high concentrations, with domination of apoptosis.

Candida albicans; C. dubliniensis; tryptophol; LC; MS;

This research was supported by Federation of European Microbiological Societies (FEMS) fellowship for Ivan Kosalec. This work was supported by grants of the Ministry of Science, Education and Sport of Republic of Croatia (N° 006-0061117-1242 and 022-0222148-2137), AFSSET grant ES 2005-012 and by an ADEME Grant (N° 0275042) for Marcel Delaforge and Olivier Puel. We thank Souria Tadrist for technical assistance. We thank the Croatian Microbiological Society (Zagreb), especially to Dr. Danko Hajsig for his support, and Prof. Derek Sullivan (Trinity College, Dublin) for donation of part of the C. dubliniensis strains used in this study.