Novel Formulated Zinc Oxide Nanoparticles Reduce Hwp1 Gene Expression Involved in Biofilm Formation in Candida albicans with Minimum Cytotoxicity Effect on Human Cells

Abstract

Background: Drug resistance in Candida species, has emerged as a major problem in the public health system worldwide. Application of nanoparticles is proposed as a novel and potential agent for reduction of drug resistance burdens. Objectives: The current study was conducted to evaluate the effects of zinc oxide nanoparticles (ZnO NPs containing chitosan and linoleic acid) on hyphae cell wall proteins (Hwp1) gene expression, a crucial gene in pathogenicity of Candida albicans, and cytotoxicity on human hepatocyte carcinoma (HepG2) cells as well as the production of Reactive Oxygen Species (ROS). Methods: The effects of novel ZnO NPs on expression of Hwp1 gene of C. albicans was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) in comparison to fluconazole as a standard drug. Reactive Oxygen species production was examined in macrophages treated with ZnO NPs relative to non-treated cells. Also, the cytotoxicity effects of ZnO NPs were assessed using the MTT assay against HepG2 cell line. Results: The findings indicated that ZnO NPs significantly decreased the level of Hwp1 gene expression in standard and clinical isolates of C. albicans. Increased level of ROS production in macrophages was found in the presence of ZnO NPs in concentrationdependent manner compared to the control group without exposure of ZnO NPs (P = 0.001). Furthermore, ZnO NPs did not show cytotoxicity activity on HepG2 cells at different concentrations (P > 0.05). Conclusions: Taken together, the newly synthesized ZnO NPs may be a suitable candidate for inhibition of the critical gene responsible for biofilm dispersion and the control of Candida infection with limited cytotoxicity on human cells. However, more studies are required for support of its effect in vitro and in vivo.

Anticandidal Potential of Two Cyanobacteria-Synthesized Silver Nanoparticles: Effects on Growth, Cell Morphology, and Key Virulence Attributes of Candida albicans

“…The largest decrease in Hwp1 gene expression occurred with the D-SNP treatment, suggesting that the potent fungicidal activity of D-SNPs includes the inhibition of biofilm formation. Aslani et al reported that exposure to zinc oxide (ZnO)-NPs coated with chitosan-conjugated linoleic acid led to a significant reduction in Hwp1 gene expression in C. albicans , suggestive of its ability to influence biofilm formation and control Candida -related infections [ 41 ].…”

“…The Rotor-Gene Q automatically compiled the data and determined the threshold cycle (Ct) value, which was normalized to the average Ct value of the housekeeping gene (ΔCt). The relative expression level of each gene was calculated as 2 −ΔCt [ 41 , 42 ].…”

The inhibitory effects of zinc oxide nanoparticles on clinical isolates of Microsporum canis in dogs and cats

“…In the study of Aslani et al (2018), the effects of zinc oxide nanoparticles on the reduction of hyphal wall protein (Hwp1) gene expression in C. albicans were performed by the qRT-PCR method. The findings showed that zinc oxide nanoparticles significantly reduced the expression of the gene in standard and clinical isolates of C. albicans (Aslani et al, 2018).…”

Mechanisms of Antifungal Properties of Metal Nanoparticles

“…NPs exposure has been shown to inhibit the formation of biofilm [81,137,155]. Hyphae development is crucial for biofilm formation and adherence, which is required for pathogenesis and colonization.…”

“…It has been shown to confer adherence and virulence [179]. ZnO NPs decreased HWP1 gene expression in C. albicans isolates [155]. The ALS gene family encodes GPI-linked cell surface glycoproteins.…”