Abstract
Fungal infections have become a major concern in the medical community, especially those caused by Candida spp. Within this species, Candida albicans stands out for being an opportunistic commensal fungus that can cause superficial and invasive infections. Current antifungal therapy involves the local and/or systemic use of drugs such as azoles, polyenes, and echinocandins. These antifungals are based on highly specific target sites, and the development of resistance may occur with changes in the enzymatic pathways that serve as the drug targets. Thus, the development of new antifungal drugs is highly recommended to prevent drug resistance. The present investigation evaluated the antifungal activity of silver-containing microcrystals such as silver vanadate (α-AgVO3), silver tungstate (α-Ag2WO4), and silver molybdate (β-Ag2MoO4). In addition to having antimicrobial activity, such compounds should not cause damage to underlying tissues. Thus, to better assess the biocompatibility of new compounds, a new three-dimensional (3D) coculture model involving three cell lines was developed. The validation of the model was based on fluorescent markers and confocal laser microscopy. The biocompatibility of silver-containing microcrystals was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 3D coculture was infected with C. albicans biofilm and challenged with α-AgVO3, α-Ag2WO4, and β-Ag2MoO4. The action of microcrystals on C. albicans biofilm was evaluated by colony-forming units (CFU/ml) and LIVE/DEAD staining. In addition, production of proinflammatory cytokines interleukin 6 (IL-6), IL-8, IL-1β, and tumor necrosis factor α (TNF-α) was measured by cytometric bead array kit using flow cytometry. The 3D coculture model described here proved to be adequate to assess both the biocompatibility of the new materials and the infectious processes. Regarding the biocompatibility of the microcrystals, only α-AgVO3 (15.62 µg/ml) showed a decrease in cell viability. The antibiofilm activity of α-Ag2WO4 was similar to that of the standard drug (fluconazole). Although α-Ag2WO4 was able to induce the production of IL-6, IL-8, and IL-1β, no differences in cytokine production were observed between noninfected and infected models treated with this microcrystal. β-Ag2MoO4 inhibits the production of TNF-α in the infected model; however, it showed no antibiofilm activity. Based on the biocompatibility and antifungal findings, α-Ag2WO4 is a promising material for treating C. albicans infection.
Highlights
Opportunistic fungal infections have been described as important causes of morbidity and mortality (Naglik et al, 2017)
The pathophysiology of C. albicans is closely influenced by several virulence factors such as the capacity to adhere to host tissues, the secretion of hydrolytic enzymes, and the ability to form biofilm, a highly organized structure that protects the microorganism from environmental changes, including antifungal agents (Sardi et al, 2013)
All materials were structurally characterized in order to observe their respective crystalline phases, as well as their purity. By both X-ray diffraction (XRD) and micro-Raman spectroscopy (Figure 1), it was possible to identify the formation of the monoclinic phase in α-AgVO3, characteristic of such compound, with space group C2/c, in agreement with the Inorganic Crystal Structure Database (ICSD), card no. 50645
Summary
Opportunistic fungal infections have been described as important causes of morbidity and mortality (Naglik et al, 2017). Local and/or systemic antifungal therapy includes the use of several drugs to treat C. albicans infections, with echinocandins, polyenes, and azoles being the most commonly used. These drugs act by preventing the synthesis or binding to components of the cell membrane of fungi, such as ergosterol, causing their death (Andriole, 2000). Despite their relatively good performance and clinical success, the prolonged use of these antifungals can cause kidney and liver damage (Andriole, 2000). Identifying novel multitarget antifungal agents to overcome these limitations represents an urgent need in the field
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
