| Autor: |
Niazy AA; Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.; Molecular and Cell Biology Laboratory, Prince Naif bin AbdulAziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia., Lambarte RNA; Molecular and Cell Biology Laboratory, Prince Naif bin AbdulAziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia., Sumague TS; Molecular and Cell Biology Laboratory, Prince Naif bin AbdulAziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia., Vigilla MGB; Molecular and Cell Biology Laboratory, Prince Naif bin AbdulAziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia., Bin Shwish NM; Molecular and Cell Biology Laboratory, Prince Naif bin AbdulAziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia., Kamalan R; Research Center, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia., Daeab EK; Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia., Aljehani NM; Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia. |
| Abstrakt: |
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 . |
