FTY720 Reduces the Biomass of Biofilms in Pseudomonas aeruginosa in a Dose-Dependent Manner.

Pseudomonas aeruginosa, a nosocomial pathogen, has strong biofilm capabilities, representing the main source of infection in the human body. Repurposing existing drugs has been explored as an alternative strategy to combat emerging antibiotic-resistant pathogens. Fingolimod hydrochloride (FTY720), an immunomodulatory drug for multiple sclerosis, has shown promising antimicrobial effects against some ESKAPE pathogens. Therefore, the effects of FTY720 on the biofilm capabilities of Pseudomonas aeruginosa were investigated in this study. It was determined that FTY720 inhibited the growth of P. aeruginosa PAO1 at 100 µM. The significant reduction in PAO1 cell viability was observed to be dose-dependent. Additional cytotoxicity analysis on human cell lines showed that FTY720 significantly reduced viabilities at sub-inhibitory concentrations of 25-50 µM. Microtiter assays and confocal analysis confirmed reductions in biofilm mass and thickness and the cell survivability ratio in the presence of FTY720. Similarly, virulence production and biofilm-related gene expression (rhlA, rhlB, pilA, pilI, fliC, fliD and algR) were determined. The results demonstrate that pigment production was affected and quantitative real-time PCR analysis showed a variable degree of reduced gene expression in response to FTY720 at 12.5-50 µM. These findings suggest that FTY720 could be repurposed as an alternative antibiofilm agent against Pseudomonas aeruginosa.

The Effectiveness of Silver Nanoparticles Mixed with Calcium Hydroxide against Candida albicans: An Ex Vivo Analysis.

INTRODUCTION: The purpose of this study was to assess the antifungal activity of silver nanoparticles (AgNPs) in combination with calcium hydroxide (Ca(OH)2) against Candida albicans (C. albicans). METHODS: AgNPs was mixed with pure Ca(OH)2 powder in an aqueous base. A standard suspension (1 × 108 bacterial cells/mL) of C. albicans was prepared in a 96-well plate and incubated on shaker at 37 °C in 100% humidity to allow fungal biofilm formation in infected dentin slices (n = 98). The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of AgNPs alone or with Ca(OH)2 were determined. The samples were separately placed in 24-well tissue culture plates and divided into three experimental groups (0.03, 0.04, and 0.06) and three control groups; negative (saline) and positive chlorhexidine gel and Ca(OH)2. Quantitative measurements of fungal activity by XTT colorimetric assay and qualitative measurements using confocal laser microscopy and scanning electron microscopy were performed. RESULTS: The cell viability of C. albicans in the experimental groups was significantly reduced compared to the negative control group. The combination of (AgNPs (0.04%) and Ca(OH)2) was the most potent against C. albicans. CONCLUSIONS: The findings demonstrated that combining silver nanoparticles with Ca(OH)2 was more effective against C. albicans biofilm compared to Ca(OH)2 alone, suggesting a combing effect.