The existence of programmed cell death (PCD) in yeast and its significance to simple unicellular organisms is still questioned. However, such doubts usually do not reflect the fact that microorganisms in nature exist predominantly within structured, multicellular communities capable of differentiation, in which a profit of individual cells is subordinated to a profit of populations. In this study, we show that some PCD features naturally appear during the development of multicellular Saccharomyces cerevisiae colonies. An ammonia signal emitted by aging colonies triggers metabolic changes that localize yeast death only in the colony center. The remaining population can exploit the released nutrients and survives. In colonies defective in Sok2p transcription factor that are unable to produce ammonia (Váchová, L., F. Devaux, H. Kucerova, M. Ricicova, C. Jacq, and Z. Palková. 2004. J. Biol. Chem. 279:37973–37981), death is spread throughout the whole population, thus decreasing the lifetime of the colony. The absence of Mca1p metacaspase or Aif1p orthologue of mammalian apoptosis-inducing factor does not prevent regulated death in yeast colonies.

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. InSaccharomyces cerevisiaecolonies, 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 H₂O₂-homeostasis between the cytosol and mitochondria. InCandida albicansbiofilms, 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.

Our present in‐depth knowledge of the physiology and regulatory mechanisms of microorganisms has arisen from our ability to remove them from their natural, complex ecosystems into pure liquid cultures. These cultures are grown under optimized laboratory conditions and allow us to study microorganisms as individuals. However, microorganisms naturally grow in conditions that are far from optimal, which causes them to become organized into multicellular communities that are better protected against the harmful environment. Moreover, this multicellular existence allows individual cells to differentiate and acquire specific properties, such as forming resistant spores, which benefit the whole population. The relocation of natural microorganisms to the laboratory can result in their adaptation to these favourable conditions, which is accompanied by complex changes that include the repression of some protective mechanisms that are essential in nature. Laboratory microorganisms that have been cultured for long periods under optimized conditions might therefore differ markedly from those that exist in natural ecosystems.

On solid substrate, growing yeast colonies alternately acidify and alkalinize the medium. Using morphological, cytochemical, genetic, and DNA microarray approaches, we characterized six temporal steps in the “acid-to-alkali” colony transition. This transition is connected with the production of volatile ammonia acting as starvation signal between colonies. We present evidence that the three membrane proteins Ato1p, Ato2p, and Ato3p, members of the YaaH family, are involved in ammonia production in Saccharomyces cerevisiae colonies. The acid-to-alkali transition is connected with decrease of mitochondrial oxidative catabolism and by peroxisome activation, which in parallel with activation of biosynthetic pathways contribute to decrease the general stress level in colonies. These metabolic features characterize a novel survival strategy used by yeast under starvation conditions prevalent in nature.