title: Analysis of validamycin as a potential antifungal compound against Candida albicans.
abstract: Validamycin A has been successfully applied in the fight against phytopathogenic fungi. Here, the putative antifungal effect of this pseudooligosaccharide against the prevalent human pathogen Candida albicans was examined. Validamycin A acts as a potent competitive inhibitor of the cell-wall-linked acid trehalase (Atc1p). The estimated MIC50 for the C. albicans parental strain CEY.1 was 500 mg/l. The addition of doses below MIC50 to exponentially growing CEY.1 cells caused a slight reduction in cell growth. A concentration of 1 mg/ml was required to achieve a significant degree of cell killing. The compound was stable as evidenced by the increased reduction of cell growth with increasing incubation time. A homozygous atc1delta/atc1delta mutant lacking functional Atc1p activity showed greater resistance to the drug. The antifungal power of validamycin A was limited compared with the drastic lethal action caused by exposure to amphotericin B. The endogenous content of trehalose rose significantly upon validamycin and amphotericin B addition. Neither serum-induced hypha formation nor the level of myceliation recorded in macroscopic colonies were affected by exposure to validamycin A. Our results suggest that, although validamycin A cannot be considered a clinically useful antifungal against C. albicans, its mechanism of action and antifungal properties provide the basis for designing new, clinically interesting, antifungal-related compounds.
authors.forename: José P
authors.initials: JP
authors.lastname: Guirao-Abad
authors.forename: Ruth
authors.initials: R
authors.lastname: Sánchez-Fresneda
authors.forename: Eulogio
authors.initials: E
authors.lastname: Valentín
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Esparza
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Argüelles
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D002177:Candidiasis / Q000382:microbiology; D002473:Cell Wall / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D014198:Trehalase / Q000235:genetics / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D007294:Inositol; C003749:validamycins; D014198:Trehalase