Therapeutic Potential of Thiazolidinedione-8 as an Antibiofilm Agent against Candida albicans
| Autor: | Itzhak Polacheck, Mark Feldman, Michael Friedman, Doron Steinberg, Abed Al-Quntar |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Virulence Factors
Gene Expression lcsh:Medicine Mycology Pathogenesis Biology Pathology and Laboratory Medicine Microbiology Microbial Ecology Cell Line Fungal Proteins Mice Minimum inhibitory concentration Gene Expression Regulation Fungal Candida albicans Gene expression Genetics Medicine and Health Sciences Animals Fungal Biochemistry lcsh:Science Microbial Pathogens Fungal Pathogens Fungal protein Multidisciplinary Ecology lcsh:R Organisms Fungi Fungal Diseases Biofilm Biology and Life Sciences biology.organism_classification Corpus albicans Quorum sensing Infectious Diseases Medical Microbiology Cell culture Biofilms Host-Pathogen Interactions Thiazolidinediones lcsh:Q Pathogens Bacterial Biofilms Research Article |
| Zdroj: | PLoS ONE, Vol 9, Iss 5, p e93225 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8) to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC). Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans-GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our compound. Our results indicate that S-8 holds a novel antibiofilm therapeutic mean in the treatment and prevention of biofilm-associated C. albicans infections. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|