Back to Search
Start Over
Analysis of validamycin as a potential antifungal compound against Candida albicans.
- Source :
-
International microbiology : the official journal of the Spanish Society for Microbiology [Int Microbiol] 2013 Dec; Vol. 16 (4), pp. 217-25. - Publication Year :
- 2013
-
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.
- Subjects :
- Candida albicans enzymology
Candida albicans genetics
Candida albicans growth & development
Candidiasis microbiology
Cell Wall drug effects
Cell Wall enzymology
Cell Wall genetics
Fungal Proteins genetics
Fungal Proteins metabolism
Gene Expression Regulation, Fungal drug effects
Humans
Inositol pharmacology
Microbial Sensitivity Tests
Trehalase genetics
Trehalase metabolism
Antifungal Agents pharmacology
Candida albicans drug effects
Inositol analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1139-6709
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International microbiology : the official journal of the Spanish Society for Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 25102722
- Full Text :
- https://doi.org/10.2436/20.1501.01.197