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Abstract Objective Candidiasis is one of the most opportunistic fungal infections in immunocompromised patients. The emergence of multidrug-resistant Candida species necessitates the development of novel antifungal agents. Seeking to the discovery of natural antifungal agents, this study aimed to synthesize a novel formulated nanocomposite containing Indolicidin (IN), antimicrobial peptide, and Graphene oxide (GO), kind of nanomaterial, against Candida growth using in vitro and in vivo experiments for the first time. Methods The formulated nanocomposite (GO-IN) synthetized and was characterized using scanning electron microscopy, X-ray power diffraction, and fourier transform infrared method analysis. The in vitro antifungal activity of fluconazole (FLU), GO, IN, and GO-IN was determined against Candida albicans (C. albicans) compared to control groups, cell cytotoxicity assay on human intestinal epithelial cells (IEP) and hemolytic activities were performed. Moreover, in vivo experiments of nanocomposite were assessed in BALB/c mice. Results Our results showed that nanocomposite had the highest inhibitory effect against C. albicans (MIC 3.12 μg/mL) compared with flu (MIC 4 μg/mL), IN (MIC 12.5 μg/mL), and GO (MIC 6.25 μg/mL). Viability of human intestinal cell line at the MIC concentration (3.12 μg/mL) of nanocomposite (GO-IN) was detected as 60% (P < 0.05). The results of hemolytic activity showed that nanocomposite cause 2.73% of red blood cell membrane damage. For in vivo experiments, infected mice were successfully treated with GO-IN once a day within 7 days. GO-IN treated group eliminated the Candida infection in the spleen and liver of BALB/c mice (P = 0.001) similar to fluconazole. There was no significant difference in histological manifestations between flu and GO-IN groups. Conclusion This study suggests that synergistic combination of GO and IN provide a new option, representing a potential therapeutic efficiency against disseminated candidiasis in an animal model as well as might be used as adjunct therapy in the management of candidiasis. However, further investigation is needed to evaluate the efficacy of the nanocomposite. [ABSTRACT FROM AUTHOR]

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The present study was designed to discover novel biomarkers involved in voriconazole resistance in clinical isolates of Aspergillus flavus. Two voriconazole non-wild-type and two voriconazole-wild-type A. flavus clinical isolates were selected to evaluate possible molecular mechanism involved in A. flavus resistance to voriconazole using the mutation assessment, Quantitative real- time PCR of cyp51A and cyp51C genes and complementary DNA- amplified fragment length polymorphism technique. No mutations were seen in the cyp51A and cyp51C genes in voriconazole non-wild-type isolates compared to wild- type and reference strains. Regarding to mRNA expression results, no changes were observed in expression fold of cyp51A and cyp51C mRNA expression level in first non- wild- type isolate compared to wild-type isolate. For second isolate cyp51C mRNA expression level was down regulated (5.6 fold). The set of genes including ABC fatty acid transporter XM- 002375835 and aldehydereductase XM- 002376518 and three unknown functional genes were identified. Based on results, the over-expression of AKR1 and ABC fatty acid transporter in the voriconazole non- wild- type isolates suggests these genes could represent a novel molecular marker linked to the voriconazole resistance in A. flavus. The results obtained in this study showed a novel finding as the authors identified AKR1 and ABC fatty acid transporter genes as possible voriconazole target genes in Iranian clinical isolates of A. flavus. [ABSTRACT FROM AUTHOR]