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 microg/mL to 191 microg/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.
Institute of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39, Zagreb, Republic of Croatia. ikosalec@pharma.hr
Ivan
I
Kosalec
Olivier
O
Puel
Marcel
M
Delaforge
Nevenka
N
Kopjar
Roberto
R
Antolovic
Dubravko
D
Jelic
Biserka
B
Matica
Pierre
P
Galtier
Stjepan
S
Pepeljnjak
D017209:Apoptosis / Q000187:drug effects; D002176:Candida albicans / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013058:Mass Spectrometry; D009183:Mycotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D009336:Necrosis
D009183:Mycotoxins