Antifungal activity and mechanism of action of dichloromethane extract fraction A from Streptomyces libani against Aspergillus fumigatus

Aims This study aimed to investigate the mechanism of antifungal action of Streptomyces libani dichloromethane extract fraction A (DCEFA) against Aspergillus fumigatus and the host cytotoxicity. Methods and Results DCEFA was purified from S. libani by autobiography and showed strong antifungal activity against A. fumigatus. A combination of electron microscopy, cell permeability assays, total oxidant status (TOS) assay, cell cytotoxicity assay and haemolysis activity was carried out to determine the target site of DCEFA. Exposure of A. fumigatus to DCEFA caused the damage to membranous cellular structures and increased release of cellular materials, potassium ions and TOS production. DCEFA was bound to ergosterol but did not affect fungal cell wall and ergosterol content. DCEFA did not show any obvious haemolytic activity for RBCs and toxicity against HEK-293 cell line. Conclusions DCEFA may inhibit A. fumigatus growth by targeting fungal cell membrane which results in the leakage of potassium ions and other cellular components, TOS production and final cell death. Significance and Impact of the Study DCEFA of S. libani could be considered as a potential source of novel antifungals which may be useful for drug development against A. fumigatus as a life-threatening human pathogen.

Automated summary

DCEFA from S. libani inhibits the growth of A. fumigatus by targeting fungal cell membrane, leading to leakage of potassium ions and cellular components, TOS production, and cell death. This extract shows potential as a novel antifungal agent for drug development against A. fumigatus, a life-threatening human pathogen.