Nejvíce citovaný článek - PubMed ID 15939758
Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia
Cell death is a natural part of the development of multicellular organisms and is central to their physiological and pathological states. However, the existence of regulated cell death in unicellular microorganisms, including eukaryotic and prokaryotic microbes, has been a topic of debate. One reason for the continued debate is the lack of obvious benefit from cell death in the context of a single cell. However, unicellularity is relative, as most of these microbes dwell in communities of varying complexities, often with complicated spatial organization. In these spatially organized microbial communities, such as yeast and bacterial colonies and biofilms growing on solid surfaces, cells differentiate into specialized types, and the whole community often behaves like a simple multicellular organism. As these communities develop and age, cell death appears to offer benefits to the community as a whole. This review explores the potential roles of cell death in spatially organized communities of yeasts and draws analogies to similar communities of bacteria. The natural dying processes in microbial cell communities are only partially understood and may result from suicidal death genes, (self-)sabotage (without death effectors), or from non-autonomous mechanisms driven by interactions with other differentiated cells. We focus on processes occurring during the stratification of yeast colonies, the formation of the extracellular matrix in biofilms, and discuss potential roles of cell death in shaping the organization, differentiation, and overall physiology of these microbial structures.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Single-celled yeasts form spatially structured populations - colonies and biofilms, either alone (single-species biofilms) or in cooperation with other microorganisms (mixed-species biofilms). Within populations, yeast cells develop in a coordinated manner, interact with each other and differentiate into specialized cell subpopulations that can better adapt to changing conditions (e.g. by reprogramming metabolism during nutrient deficiency) or protect the overall population from external influences (e.g. via extracellular matrix). Various omics tools together with specialized techniques for separating differentiated cells and in situ microscopy have revealed important processes and cell interactions in these structures, which are summarized here. Nevertheless, current knowledge is still only a small part of the mosaic of complexity and diversity of the multicellular structures that yeasts form in different environments. Future challenges include the use of integrated multi-omics approaches and a greater emphasis on the analysis of differentiated cell subpopulations with specific functions.
- Klíčová slova
- Biofilms, Cell differentiation, Colonies, Multicellular yeast structures, Regulation, Spatial community structure,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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.
- Klíčová slova
- Flo11p adhesin, cell adhesion, cell organization, colonies and biofilms, laboratory and wild Saccharomyces cerevisiae strains, structure development, yeast multicellular structures,
- MeSH
- biofilmy * MeSH
- buněčné dělení MeSH
- membránové glykoproteiny genetika metabolismus MeSH
- mikrobiální interakce MeSH
- mutace MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae cytologie metabolismus fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- FLO11 protein, S cerevisiae MeSH Prohlížeč
- membránové glykoproteiny MeSH
- Saccharomyces cerevisiae - proteiny MeSH
We present the spatiotemporal metabolic differentiation of yeast cell subpopulations from upper, lower, and margin regions of colonies of different ages, based on comprehensive transcriptomic analysis. Furthermore, the analysis was extended to include smaller cell subpopulations identified previously by microscopy within fully differentiated U and L cells of aged colonies. New data from RNA-seq provides both spatial and temporal information on cell metabolic reprogramming during colony ageing and shows that cells at marginal positions are similar to upper cells, but both these cell types are metabolically distinct from cells localized to lower colony regions. As colonies age, dramatic metabolic reprogramming occurs in cells of upper regions, while changes in margin and lower cells are less prominent. Interestingly, whereas clear expression differences were identified between two L cell subpopulations, U cells (which adopt metabolic profiles, similar to those of tumor cells) form a more homogeneous cell population. The data identified crucial metabolic reprogramming events that arise de novo during colony ageing and are linked to U and L cell colony differentiation and support a role for mitochondria in this differentiation process.
Mitochondrial retrograde signaling mediates communication from altered mitochondria to the nucleus and is involved in many normal and pathophysiological changes, including cell metabolic reprogramming linked to cancer development and progression in mammals. The major mitochondrial retrograde pathway described in yeast includes three activators, Rtg1p, Rtg2p and Rtg3p, and repressors, Mks1p and Bmh1p/Bmh2p. Using differentiated yeast colonies, we show that Mks1p-Rtg pathway regulation is complex and includes three branches that divergently regulate the properties and fate of three specifically localized cell subpopulations via signals from differently altered mitochondria. The newly identified RTG pathway-regulated genes ATO1/ATO2 are expressed in colonial upper (U) cells, the cells with active TORC1 that metabolically resemble tumor cells, while CIT2 is a typical target induced in one subpopulation of starving lower (L) cells. The viability of the second L cell subpopulation is strictly dependent on RTG signaling. Additional co-activators of Rtg1p-Rtg3p specific to particular gene targets of each branch are required to regulate cell differentiation.
- Klíčová slova
- ageing and longevity, development and differentiation, mitochondrial retrograde signaling,
- MeSH
- buněčná diferenciace fyziologie MeSH
- geny hub fyziologie MeSH
- mitochondrie metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae fyziologie MeSH
- signální transdukce fyziologie MeSH
- viabilita buněk fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Saccharomyces cerevisiae - proteiny MeSH
The SUN family is comprised of proteins that are conserved among various yeasts and fungi, but that are absent in mammals and plants. Although the function(s) of these proteins are mostly unknown, they have been linked to various, often unrelated cellular processes such as those connected to mitochondrial and cell wall functions. Here we show that three of the four Saccharomyces cerevisiae SUN family proteins, Uth1p, Sim1p and Sun4p, are efficiently secreted out of the cells in different growth phases and their production is affected by the level of oxygen. The Uth1p, Sim1p, Sun4p and Nca3p are mostly synthesized during the growth phase of both yeast liquid cultures and colonies. Culture transition to slow-growing or stationary phases is linked with a decreased cellular concentration of Sim1p and Sun4p and with their efficient release from the cells. In contrast, Uth1p is released mainly from growing cells. The synthesis of Uth1p and Sim1p, but not of Sun4p, is repressed by anoxia. All four proteins confer cell sensitivity to zymolyase. In addition, Uth1p affects cell sensitivity to compounds influencing cell wall composition and integrity (such as Calcofluor white and Congo red) differently when growing on fermentative versus respiratory carbon sources. In contrast, Uth1p is essential for cell resistance to boric acids irrespective of carbon source. In summary, our novel findings support the hypothesis that SUN family proteins are involved in the remodeling of the yeast cell wall during the various phases of yeast culture development and under various environmental conditions. The finding that Uth1p is involved in cell sensitivity to boric acid, i.e. to a compound that is commonly used as an important antifungal in mycoses, opens up new possibilities of investigating the mechanisms of boric acid's action.
- MeSH
- benzensulfonáty metabolismus farmakologie MeSH
- buněčná stěna metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- glukosidasy genetika metabolismus MeSH
- intracelulární prostor metabolismus MeSH
- kyseliny borité metabolismus farmakologie MeSH
- membránové proteiny genetika metabolismus MeSH
- mitochondriální proteiny genetika metabolismus MeSH
- proteiny teplotního šoku genetika metabolismus MeSH
- regulace genové exprese u hub MeSH
- represorové proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae účinky léků genetika růst a vývoj metabolismus MeSH
- spotřeba kyslíku * MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzensulfonáty MeSH
- C.I. Fluorescent Brightening Agent 28 MeSH Prohlížeč
- glukosidasy MeSH
- kyseliny borité MeSH
- membránové proteiny MeSH
- mitochondriální proteiny MeSH
- proteiny teplotního šoku MeSH
- represorové proteiny MeSH
- Saccharomyces cerevisiae - proteiny MeSH
- SIM1 protein, S cerevisiae MeSH Prohlížeč
- Sun4 protein, S cerevisiae MeSH Prohlížeč
- transkripční faktory bHLH MeSH
- UTH1 protein, S cerevisiae MeSH Prohlížeč
During their development and aging on solid substrates, yeast giant colonies produce ammonia, which acts as a quorum sensing molecule. Ammonia production is connected with alkalization of the surrounding medium and with extensive reprogramming of cell metabolism. In addition, ammonia signaling is important for both horizontal (colony centre versus colony margin) and vertical (upper versus lower cell layers) colony differentiations. The centre of an aging differentiated giant colony is thus composed of two major cell subpopulations, the subpopulation of long-living, metabolically active and stress-resistant cells that form the upper layers of the colony and the subpopulation of stress-sensitive starving cells in the colony interior. Here, we show that microcolonies originating from one cell pass through similar developmental phases as giant colonies. Microcolony differentiation is linked to ammonia signaling, and cells similar to the upper and lower cells of aged giant colonies are formed even in relatively young microcolonies. A comparison of the properties of these cells revealed a number of features that are similar in microcolonies and giant colonies as well as a few that are only typical of chronologically aged giant colonies. These findings show that colony age per se is not crucial for colony differentiation.
- MeSH
- amoniak metabolismus MeSH
- kvasinky metabolismus MeSH
- signální transdukce fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amoniak MeSH
When growing on solid surfaces, yeast, like other microorganisms, develops organized multicellular populations (colonies and biofilms) that are composed of differentiated cells with specialized functions. Life within these populations is a prevalent form of microbial existence in natural settings that provides the cells with capabilities to effectively defend against environmental attacks as well as efficiently adapt and survive long periods of starvation and other stresses. Under such circumstances, the fate of an individual yeast cell is subordinated to the profit of the whole population. In the past decade, yeast colonies, with their complicated structure and high complexity that are also developed under laboratory conditions, have become an excellent model for studies of various basic cellular processes such as cell interaction, signaling, and differentiation. In this paper, we summarize current knowledge on the processes related to chronological aging, adaptation, and longevity of a colony cell population and of its differentiated cell constituents. These processes contribute to the colony ability to survive long periods of starvation and mostly differ from the survival strategies of individual yeast cells.
- MeSH
- biologické modely * MeSH
- časové faktory MeSH
- dlouhověkost fyziologie MeSH
- fyziologická adaptace * MeSH
- kvasinky cytologie růst a vývoj metabolismus fyziologie MeSH
- lidé MeSH
- počet mikrobiálních kolonií MeSH
- životní prostředí * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
One of the universal traits of microorganisms is their ability to form multicellular structures, the cells of which differentiate and communicate via various signaling molecules. Reactive oxygen species (ROS), and hydrogen peroxide in particular, have recently become well-established signaling molecules in higher eukaryotes, but still little is known about the regulatory functions of ROS in microbial structures. Here we summarize current knowledge on the possible roles of ROS during the development of colonies and biofilms, representatives of microbial multicellularity. In Saccharomyces cerevisiae colonies, ROS are predicted to participate in regulatory events involved in the induction of ammonia signaling and later on in programmed cell death in the colony center. While the latter process seems to be induced by the total ROS, the former event is likely to be regulated by ROS-homeostasis, possibly H(2)O(2)-homeostasis between the cytosol and mitochondria. In Candida albicans biofilms, the predicted signaling role of ROS is linked with quorum sensing molecule farnesol that significantly affects biofilm formation. In bacterial biofilms, ROS induce genetic variability, promote cell death in specific biofilm regions, and possibly regulate biofilm development. Thus, the number of examples suggesting ROS as signaling molecules and effectors in the development of microbial multicellularity is rapidly increasing.
- MeSH
- Bacteria cytologie metabolismus MeSH
- fyziologická adaptace * MeSH
- houby cytologie metabolismus MeSH
- mikrobiální společenstva fyziologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- signální transdukce * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- reaktivní formy kyslíku MeSH
This review summarizes the main results obtained in the fields of general and molecular microbiology and microbial genetics at the Institute of Microbiology of the Academy of Sciences of the Czech Republic (AS CR) [formerly Czechoslovak Academy of Sciences (CAS)] over more than 50 years. Contribution of the founder of the Institute, academician Ivan Málek, to the introduction of these topics into the scientific program of the Institute of Microbiology and to further development of these studies is also included.
- MeSH
- akademie a ústavy dějiny MeSH
- dějiny 20. století MeSH
- mikrobiální genetika dějiny MeSH
- molekulární biologie dějiny MeSH
- Check Tag
- dějiny 20. století MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH