Saccharomyces cerevisiae is a mainly beneficial yeast, widely used in the food industry. However, there is growing evidence of its potential pathogenicity, leading to fungemia and invasive infections. The medical impact of yeast pathogens depends on formation of biofilms: multicellular structures, protected from the environment. Cell adhesion is a prerequisite of biofilm formation. We investigated the adherence of wild and genetically modified S. cerevisiae strains, formation of solid-liquid interface biofilms and associated regulation. Planktonic and static cells of wild strain BRF adhered and formed biofilms in glucose-free medium. Tup1p and Cyc8p were key positive and negative regulators, respectively. Glucose caused increased Cyc8p levels and blocked cell adhesion. Even low glucose levels, comparable with levels in the blood, allowed biofilm dispersal and release of planktonic cells. Cyc8p could thus modulate cell adhesion in different niches, dependently on environmental glucose level, e.g., high-glucose blood versus low-glucose tissues in host organisms.

• MeSH
• bakteriální adheze MeSH
• biofilmy růst a vývoj   MeSH
• glukosa metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• kultivační média chemie   MeSH
• mutace MeSH
• povrchové vlastnosti MeSH
• regulace genové exprese u hub MeSH
• represorové proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Yeast biofilms are complex multicellular structures, in which the cells are well protected against drugs and other treatments and thus highly resistant to antifungal therapies. Colony biofilms represent an ideal system for studying molecular mechanisms and regulations involved in development and internal organization of biofilm structure as well as those that are involved in fungal domestication. We have identified here antagonistic functional interactions between transcriptional regulators Cyc8p and Tup1p that modulate the life-style of natural S. cerevisiae strains between biofilm and domesticated mode. Herein, strains with different levels of Cyc8p and Tup1p regulators were constructed, analyzed for processes involved in colony biofilm development and used in the identification of modes of regulation of Flo11p, a key adhesin in biofilm formation. Our data show that Tup1p and Cyc8p regulate biofilm formation in the opposite manner, being positive and negative regulators of colony complexity, cell-cell interaction and adhesion to surfaces. Notably, in-depth analysis of regulation of expression of Flo11p adhesin revealed that Cyc8p itself is the key repressor of FLO11 expression, whereas Tup1p counteracts Cyc8p's repressive function and, in addition, counters Flo11p degradation by an extracellular protease. Interestingly, the opposing actions of Tup1p and Cyc8p concern processes crucial to the biofilm mode of yeast multicellularity, whereas other multicellular processes such as cell flocculation are co-repressed by both regulators. This study provides insight into the mechanisms regulating complexity of the biofilm lifestyle of yeast grown on semisolid surfaces.

• MeSH
• biofilmy * MeSH
• buněčná adheze fyziologie   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• membránové glykoproteiny genetika   metabolismus   MeSH
• mezibuněčná komunikace fyziologie   MeSH
• regulace genové exprese u hub * MeSH
• represorové proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Yeasts create multicellular structures of varying complexity, such as more complex colonies and biofilms and less complex flocs, each of which develops via different mechanisms. Colony biofilms originate from one or more cells that, through growth and division, develop a complicated three-dimensional structure consisting of aerial parts, agar-embedded invasive parts and a central cavity, filled with extracellular matrix. In contrast, flocs arise relatively quickly by aggregation of planktonic cells growing in liquid cultures after they reach the appropriate growth phase and/or exhaust nutrients such as glucose. Creation of both types of structures is dependent on the presence of flocculins: Flo11p in the former case and Flo1p in the latter. We recently showed that formation of both types of structures by wild Saccharomyces cerevisiae strain BR-F is regulated via transcription regulators Tup1p and Cyc8p, but in a divergent manner. Biofilm formation is regulated by Cyc8p and Tup1p antagonistically: Cyc8p functions as a repressor of FLO11 gene expression and biofilm formation, whereas Tup1p counteracts the Cyc8p repressor function and positively regulates biofilm formation and Flo11p expression. In addition, Tup1p stabilizes Flo11p probably by repressing a gene coding for a cell wall or extracellular protease that is involved in Flo11p degradation. In contrast, formation of BR-F flocs is co-repressed by the Cyc8p-Tup1p complex. These findings point to different mechanisms involved in yeast multicellularity.

• MeSH
• biofilmy MeSH
• buněčná stěna genetika   metabolismus   MeSH
• druhová specificita MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• regulace genové exprese u hub * MeSH
• represorové proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae klasifikace   genetika   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH