ABSTRACT

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.

During development of yeast colonies, various cell subpopulations form, which differ in their properties and specifically localize within the structure. Three branches of mitochondrial retrograde (RTG) signaling play a role in colony development and differentiation, each of them activating the production of specific markers in different cell types. Here, aiming to identify proteins and processes controlled by the RTG pathway, we analyzed proteomes of individual cell subpopulations from colonies of strains, mutated in genes of the RTG pathway. Resulting data, along with microscopic analyses revealed that the RTG pathway predominantly regulates processes in U cells, long-lived cells with unique properties, which are localized in upper colony regions. Rtg proteins therein activate processes leading to amino acid biosynthesis, including transport of metabolic intermediates between compartments, but also repress expression of mitochondrial ribosome components, thus possibly contributing to reduced mitochondrial translation in U cells. The results reveal the RTG pathway’s role in activating metabolic processes, important in U cell adaptation to altered nutritional conditions. They also point to the important role of Rtg regulators in repressing mitochondrial activity in U cells.

Multicellular structures formed by yeasts and other microbes are valuable models for investigating the processes of cell–cell interaction and pattern formation, as well as cell signaling and differentiation. These processes are essential for the organization and development of diverse microbial communities that are important in everyday life. Two major types of multicellular structures are formed by yeast Saccharomyces cerevisiae on semisolid agar. These are colonies formed by laboratory or domesticated strains and structured colony biofilms formed by wild strains. These structures differ in spatiotemporal organization and cellular differentiation. Using state-of-the-art microscopy and mutant analysis, we investigated the distribution of cells within colonies and colony biofilms and the involvement of specific processes therein. We show that prominent differences between colony and biofilm structure are determined during early stages of development and are associated with the different distribution of growing cells. Two distinct cell distribution patterns were identified—the zebra-type and the leopard-type, which are genetically determined. The role of Flo11p in cell adhesion and extracellular matrix production is essential for leopard-type distribution, because FLO11 deletion triggers the switch to zebra-type cell distribution. However, both types of cell organization are independent of cell budding polarity and cell separation as determined using respective mutants.