Abstract
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 µg/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-α), 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.
Highlights
A. fumigatus is the major pathogenic agent responsible for approximately 90% of invasive pulmonary aspergillosis (IPA) cases and is considered one of the most significant invasive fungal infections of worldwide concern [1,2]
We investigated the antifungal effect of biosynthesized AgNPs using the leaf extract of A. sieberi on A. fumigatus in vitro and in vivo in an IPA mouse model
The biosynthesis of AS-AgNPs was confirmed by transmission electron microscopy, which showed that the purified AS-AgNPs were spherical in shape with a diameter range of
Summary
A. fumigatus is the major pathogenic agent responsible for approximately 90% of IPA cases and is considered one of the most significant invasive fungal infections of worldwide concern [1,2]. The risk of developing infections increases in patients with underlying debilitating diseases, such as cancer, chronic lung diseases, transplantation, or immune system impairment [3,4]. In chronic forms of IPA, A. fumigatus develops a thick biofilm that promotes its persistence [5]. Biofilm formation by A. fumigatus is reported as one of the most important virulence factors in IPA [6]. Several secondary metabolites secreted by A. fumigatus are required for infection [7], including gliotoxin (GT), a secondary metabolite that belongs to the epipolythiodioxopiperazine class of mycotoxins [8] and is found in the sera of patients with IPA [9]. GT inhibits the host immune response and is used as a potential virulence factor in IPA infection [10,11]
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