Analysis of validamycin as a potential antifungal compound against Candida albicans

Autores/as

  • José P. Guirao-Abad Microbiology Area, School of Biology, University of Murcia, Murcia.
  • Ruth Sánchez-Fresneda Microbiology Area, School of Biology, University of Murcia
  • Eulogio Valentín Department of Microbiology and Ecology, University of Valencia, Burjassot
  • María Martínez-Esparza Department of Biochemistry and Molecular Biology and Immunology, University of Murcia
  • Juan-Carlos Argüelles Microbiology Area, School of Biology, University of Murcia, Murcia

Palabras clave:

Candida albicans, Rhizoctonia solani, validamycin A, amphotericin B, trehalose

Resumen

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 atc1Δ/atc1Δ 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. [Int Microbiol 2013; 16(4):217-225]

Keywords: Candida albicans · Rhizoctonia solani · validamycin A · amphotericin B · trehalose

Biografía del autor/a

José P. Guirao-Abad, Microbiology Area, School of Biology, University of Murcia, Murcia.




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