The effect of a trehalase inhibitor, validamycin A, on the growth of Aspergillus flavus

Abstract

Aspergillus flavus is a fungus found in the environment causing keratitis, cutaneous infections, sinusitis, invasive pulmonary aspergillosis in humans. Although this fungus can be treated with antifungal agents, these main antifungal agents have many side effects. Trehalase is an enzyme for digesting trehalose into two glucose subunits and is essential for virulence in many fungi. A trehalase inhibitor, called validamycin A, has been used effectively against a rice fungal pathogen, Rhizoctonia solani. In this study, we observed that validamycin A increased trehalose levels significantly in A. flavus spores and delayed the germination of those spores. In addition, to further investigate the combinative effect of validamycin A with an antifungal agent, amphotericin B, the checkerboard assay was performed with A. flavus ATCC204304 and A. flavus clinical isolates with high minimum inhibitory concentrations (MICs) of amphotericin B. We observed that validamycin A and amphotericin B had a synergistic effect with these A. flavus clinical isolates. The cytotoxicity of validamycin A to human bronchial epithelial cells was not observed in this study. In conclusion, this study showed that validamycin A was able to inhibit the growth of A. flavus. One of the mechanisms behind the effect of validamycin A was to delay the germination of A. flavus spores. Furthermore, validamycin A also possessed a combinative effect with amphotericin B without significant cytotoxic effect on human bronchial epithelial cells.