FTY720 Reduces the Biomass of Biofilms in <i>Pseudomonas aeruginosa</i> in a Dose-Dependent Manner
<i>Pseudomonas aeruginosa</i>, 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 hydroc...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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MDPI AG,
2024-07-01T00:00:00Z.
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| Summary: | <i>Pseudomonas aeruginosa</i>, 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 <i>Pseudomonas aeruginosa</i> were investigated in this study. It was determined that FTY720 inhibited the growth of <i>P. aeruginosa</i> 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 (<i>rhlA</i>, <i>rhlB</i>, <i>pilA</i>, <i>pilI</i>, <i>fliC</i>, <i>fliD</i> and <i>algR</i>) 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 <i>Pseudomonas aeruginosa</i>. |
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| Item Description: | 10.3390/antibiotics13070621 2079-6382 |