Pharmaceutical Sciences (Oct 2024)
Negative Regulators, TUP1, NRG1, and TOR1: Possible Molecular Targets of Antibiofilm Activity of Nano-Fe3O4 in Candida albicans
Abstract
Background: Candida albicans is an opportunistic pathobiont that manifests as candidiasis. Drug-resistant biofilms hinder current treatment of candidiasis. The morphological control of filamentous growth and biofilm formation is vital for the pathogenicity of C. albicans. This study aimed to investigate the antifungal activity of magnetic iron oxide nanoparticles (nano-Fe3 O4 ) against C. albicans, their ability to inhibit pre-formed biofilms, and to examine the expression levels of negative regulators, transcriptional repressors thymidine uptake 1 (TUP1), the negative transcriptional regulator of glucose repressed genes (NRG1), and target of rapamycin (TOR1) in C. albicans pre-formed biofilms after treatment with nano-Fe3 O4 . Methods: This study examines the antifungal activity of nano-Fe3 O4 against C. albicans, its ability to inhibit pre-formed biofilms, and investigates the expression levels of negative regulators, TUP1, NRG1, and TOR1 in C. albicans pre-formed biofilms after treatment with nano-Fe3 O4 . Results: Nano-Fe3 O4 at concentrations of 2× minimum inhibitory concentration (MIC), 1× MIC, and ½× MIC showed significant inhibitory effects on C. albicans pre-formed biofilm formation by 2,3-bis (2-methoxy-4-nitro-5 sulfophenyl)-5-[(phenylamino) carbonyl])-2H-tetrazolium hydroxide (XTT), crystal violet staining and light field microscopy with a MIC of 50 μg/mL. Gene expression profiling showed that nano-Fe3 O4 upregulates targets TUP1, NRG1, and TOR1 in C. albicans pre-formed biofilms. Conclusion: Our results suggest that nano-Fe3 O4 diminishes pre-formed biofilms and may subsequently reduce the pathogenicity of C. albicans, which can be responsible for biofilm-associated infections. TUP1, NRG1, and TOR1 may be possible molecular targets in C. albicans pre-formed biofilms after treatment with nano-Fe3 O4.
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