Effective Inhibition of Invasive Pulmonary Aspergillosis by Silver Nanoparticles Biosynthesized with Artemisia sieberi Leaf Extract

Aspergillus fumigatus is one of the most common fungal pathogens that can cause a diversity of diseases ranging from invasive pulmonary aspergillosis (IPA) and aspergilloma to allergic syndromes. In this study, we investigated the antifungal effect of silver nanoparticles biosynthesized with Artemisia sieberi leaf extract (AS-AgNPs) against A. fumigatus in vitro and in vivo. The biosynthesized AS-AgNPs were characterized by imaging (transmission electron microscopy (TEM)), UV-VIS spectroscopy, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The microdilution method showed the antifungal activity of AS-AgNPs against A. fumigatus, with an MIC of 128 mu g/mL. AS-AgNPs significantly inhibited the growth of hyphae in all directions, as imaged by SEM. Additionally, TEM on biofilm revealed invaginations of the cell membrane, a change in the vacuolar system, and the presence of multilamellar bodies within vacuoles. Interestingly, AS-AgNPs displayed low cytotoxicity on the A549 human lung cell line in vitro. Treatment of an invasive pulmonary aspergillosis (IPA) mouse model with AS-AgNPs demonstrated the potency of AS-AgNPs to significantly reduce lung tissue damage and to suppress the elevated levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-17 (IL-17). The therapeutic potential of AS-AgNPs was found to be due to their direct action to suppress the fungal burden and gliotoxin production in the lungs. In addition, AS-AgNPs reduced the oxidative stress in the lungs by increasing the enzymatic activities of catalase (CAT) and superoxide dismutase (SOD). Thus, our data indicate the biosynthesized AS-AgNPs as a novel antifungal alternative treatment against aspergillosis.

Automated summary

In this study, the antifungal effect of silver nanoparticles biosynthesized with Artemisia sieberi leaf extract (AS-AgNPs) against Aspergillus fumigatus was investigated. The AS-AgNPs showed significant antifungal activity and inhibited the growth of hyphae. They also exhibited low cytotoxicity on human lung cells. In a mouse model, AS-AgNPs effectively reduced lung tissue damage, suppressed the levels of pro-inflammatory cytokines, and decreased oxidative stress. The findings suggest that AS-AgNPs have therapeutic potential as an alternative treatment for aspergillosis.