Cell differentiation, aging, and death in spatially organized yeast communities: mechanisms and consequences
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Review
PubMed
40158069
PubMed Central
PMC12432192
DOI
10.1038/s41418-025-01485-9
PII: 10.1038/s41418-025-01485-9
Knihovny.cz E-resources
- MeSH
- Biofilms growth & development MeSH
- Cell Differentiation * MeSH
- Cell Death MeSH
- Yeasts * cytology MeSH
- Saccharomyces cerevisiae * cytology MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
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.
See more in PubMed
Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell. 2011;147:742–58. PubMed PMC
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death. Cell Death Differ. 2018;25:486–541. PubMed PMC
Kulkarni M, Hardwick JM. Programmed cell death in unicellular versus multicellular organisms. Annu Rev Genet. 2023;57:435–59. PubMed PMC
Vachova L, Palkova Z. Caspases in yeast apoptosis-like death: facts and artefacts. FEMS Yeast Res. 2007;7:12–21. PubMed
Lee RE, Brunette S, Puente LG, Megeney LA. Metacaspase Yca1 is required for clearance of insoluble protein aggregates. Proc Natl Acad Sci USA. 2010;107:13348–53. PubMed PMC
Shrestha A, Brunette S, Stanford WL, Megeney LA. The metacaspase Yca1 maintains proteostasis through multiple interactions with the ubiquitin system. Cell Discov. 2019;5:6. PubMed PMC
Stolp ZD, Kulkarni M, Liu Y, Zhu C, Jalisi A, Lin S, et al. Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization. Cell Rep. 2022;39:110647. PubMed PMC
Kim H, Kim A, Cunningham KW. Vacuolar H+-ATPase (V-ATPase) promotes vacuolar membrane permeabilization and nonapoptotic death in stressed yeast. J Biol Chem. 2012;287:19029–39. PubMed PMC
Pereira C, Chaves S, Alves S, Salin B, Camougrand N, Manon S, et al. Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier. Mol Microbiol. 2010;76:1398–410. PubMed
Chaves SR, Rego A, Martins VM, Santos-Pereira C, Sousa MJ, Corte-Real M. Regulation of cell death induced by acetic acid in yeasts. Front Cell Dev Biol. 2021;9:642375. PubMed PMC
Durand PM, Ramsey G. The concepts and origins of cell mortality. Hist Philos Life Sci. 2023;45:23. PubMed PMC
Lohr JN, Galimov ER, Gems D. Does senescence promote fitness in PubMed PMC
Pepper JW, Shelton DE, Rashidi A, Asfaha SM, Durand PM. Are internal, death-promoting mechanisms ever adaptive? J Phylogen Evolut Biol. 2013;1:113.
Bridier A, Piard JC, Pandin C, Labarthe S, Dubois-Brissonnet F, Briandet R. Spatial organization plasticity as an adaptive driver of surface microbial communities. Front Microbiol. 2017;8:1364. PubMed PMC
Jo J, Price-Whelan A, Dietrich LEP. Gradients and consequences of heterogeneity in biofilms. Nat Rev Microbiol. 2022;20:593–607. PubMed PMC
Munoz-Dorado J, Marcos-Torres FJ, Garcia-Bravo E, Moraleda-Munoz A, Perez J. Myxobacteria: Moving, killing, feeding, and surviving together. Front Microbiol. 2016;7:781. PubMed PMC
Palkova Z, Vachova L. Yeast cell differentiation: lessons from pathogenic and non-pathogenic yeasts. Semin Cell Dev Biol. 2016;57:110–9. PubMed
Palkova Z, Vachova L. Spatially structured yeast communities: understanding structure formation and regulation with omics tools. Comput Struct Biotechnol J. 2021;19:5613–21. PubMed PMC
Tarnita CE. The ecology and evolution of social behavior in microbes. J Exp Biol. 2017;220:18–24. PubMed
Vachova L, Palkova Z. How structured yeast multicellular communities live, age and die? FEMS Yeast Res. 2018;18:foy033. PubMed
van Gestel J, Vlamakis H, Kolter R. Division of labor in biofilms: the ecology of cell differentiation. Microbiol Spectr. 2015;3:MB-0002–2014. PubMed
Evans CR, Kempes CP, Price-Whelan A, Dietrich LEP. Metabolic heterogeneity and cross-feeding in bacterial multicellular systems. Trends Microbiol. 2020;28:732–43. PubMed PMC
Honigberg SM. Cell signals, cell contacts, and the organization of yeast communities. Eukaryot Cell. 2011;10:466–73. PubMed PMC
McCormick JR, Flardh K. Signals and regulators that govern PubMed PMC
Rousset F, Sorek R. The evolutionary success of regulated cell death in bacterial immunity. Curr Opin Microbiol. 2023;74:102312. PubMed
Nguyen PV, Hlavacek O, Marsikova J, Vachova L, Palkova Z. Cyc8p and Tup1p transcription regulators antagonistically regulate Flo11p expression and complexity of yeast colony biofilms. PLoS Genet. 2018;14:e1007495. PubMed PMC
Vachova L, Stovicek V, Hlavacek O, Chernyavskiy O, Stepanek L, Kubinova L, et al. Flo11p, drug efflux pumps, and the extracellular matrix cooperate to form biofilm yeast colonies. J Cell Biol. 2011;194:679–87. PubMed PMC
Van Nguyen P, Plocek V, Vachova L, Palkova Z. Glucose, Cyc8p and Tup1p regulate biofilm formation and dispersal in wild PubMed PMC
Granek JA, Magwene PM. Environmental and genetic determinants of colony morphology in yeast. PLoS Genet. 2010;6:e1000823. PubMed PMC
Kuthan M, Devaux F, Janderova B, Slaninova I, Jacq C, Palkova Z. Domestication of wild PubMed
Aguilar C, Vlamakis H, Losick R, Kolter R. Thinking about PubMed PMC
Branda SS, Gonzalez-Pastor JE, Ben-Yehuda S, Losick R, Kolter R. Fruiting body formation by PubMed PMC
Stovicek V, Vachova L, Kuthan M, Palkova Z. General factors important for the formation of structured biofilm-like yeast colonies. Fungal Genet Biol. 2010;47:1012–22. PubMed
Veening JW, Kuipers OP, Brul S, Hellingwerf KJ, Kort R. Effects of phosphorelay perturbations on architecture, sporulation, and spore resistance in biofilms of PubMed PMC
Stovicek V, Vachova L, Begany M, Wilkinson D, Palkova Z. Global changes in gene expression associated with phenotypic switching of wild yeast. BMC Genomics. 2014;15:136. PubMed PMC
Holmes DL, Lancaster AK, Lindquist S, Halfmann R. Heritable remodeling of yeast multicellularity by an environmentally responsive prion. Cell. 2013;153:153–65. PubMed PMC
Tan Z, Hays M, Cromie GA, Jeffery EW, Scott AC, Ahyong V, et al. Aneuploidy underlies a multicellular phenotypic switch. Proc Natl Acad Sci USA. 2013;110:12367–72. PubMed PMC
Gibbons JG, Rinker DC. The genomics of microbial domestication in the fermented food environment. Curr Opin Genet Dev. 2015;35:1–8. PubMed PMC
Vachova L, Chernyavskiy O, Strachotova D, Bianchini P, Burdikova Z, Fercikova I, et al. Architecture of developing multicellular yeast colony: spatio-temporal expression of Ato1p ammonium exporter. Environ Microbiol. 2009;11:1866–77. PubMed
Plocek V, Vachova L, Stovicek V, Palkova Z. Cell distribution within yeast colonies and colony biofilms: How structure develops. Int J Mol Sci. 2020;21:3873. PubMed PMC
Cap M, Stepanek L, Harant K, Vachova L, Palkova Z. Cell differentiation within a yeast colony: metabolic and regulatory parallels with a tumor-affected organism. Mol Cell. 2012;46:436–48. PubMed
Palkova Z, Devaux F, Ricicova M, Minarikova L, Le Crom S, Jacq C. Ammonia pulses and metabolic oscillations guide yeast colony development. Mol Biol Cell. 2002;13:3901–14. PubMed PMC
Podholova K, Plocek V, Resetarova S, Kucerova H, Hlavacek O, Vachova L, et al. Divergent branches of mitochondrial signaling regulate specific genes and the viability of specialized cell types of differentiated yeast colonies. Oncotarget. 2016;7:15299–314. PubMed PMC
Vachova L, Hatakova L, Cap M, Pokorna M, Palkova Z. Rapidly developing yeast microcolonies differentiate in a similar way to aging giant colonies. Oxid Med Cell Longev. 2013;2013:102485. PubMed PMC
Vachova L, Kucerova H, Devaux F, Ulehlova M, Palkova Z. Metabolic diversification of cells during the development of yeast colonies. Environ Microbiol. 2009;11:494–504. PubMed
Vachova L, Cap M, Palkova Z. Yeast colonies: a model for studies of aging, environmental adaptation, and longevity. Oxid Med Cell Longev. 2012;2012:601836. PubMed PMC
Vachova L, Palkova Z. Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia. J Cell Biol. 2005;169:711–7. PubMed PMC
Marsikova J, Pavlickova M, Wilkinson D, Vachova L, Hlavacek O, Hatakova L, et al. The Whi2p-Psr1p/Psr2p complex regulates interference competition and expansion of cells with competitive advantage in yeast colonies. Proc Natl Acad Sci USA. 2020;117:15123–31. PubMed PMC
Vachova L, Plocek V, Marsikova J, Resetarova S, Hatakova L, Palkova Z. Differential stability of Gcn4p controls its cell-specific activity in differentiated yeast colonies. mBio. 2024;15:e0068924. PubMed PMC
Plocek V, Fadrhonc K, Marsikova J, Vachova L, Pokorna A, Hlavacek O, et al. Mitochondrial retrograde signaling contributes to metabolic differentiation in yeast colonies. Int J Mol Sci. 2021;22:5597. PubMed PMC
Cap M, Vachova L, Palkova Z. Longevity of U cells of differentiated yeast colonies grown on respiratory medium depends on active glycolysis. Cell Cycle. 2015;14:3488–97. PubMed PMC
Cap M, Palkova Z. The characteristics of differentiated yeast subpopulations depend on their lifestyle and available nutrients. Sci Rep. 2024;14:3681. PubMed PMC
Wilkinson D, Marsikova J, Hlavacek O, Gilfillan GD, Jezkova E, Aalokken R, et al. Transcriptome remodeling of differentiated cells during chronological ageing of yeast colonies: new insights into metabolic differentiation. Oxid Med Cell Longev. 2018;2018:4932905. PubMed PMC
Hartwell LH. Genetic control of the cell division cycle in yeast. IV. Genes controlling bud emergence and cytokinesis. Exp Cell Res. 1971;69:265–76. PubMed
Madeo F, Herker E, Maldener C, Wissing S, Lachelt S, Herlan M, et al. A caspase-related protease regulates apoptosis in yeast. Mol Cell. 2002;9:911–7. PubMed
Wissing S, Ludovico P, Herker E, Buttner S, Engelhardt SM, Decker T, et al. An AIF orthologue regulates apoptosis in yeast. J Cell Biol. 2004;166:969–74. PubMed PMC
DeBerardinis RJ, Cheng T. Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene. 2010;29:313–24. PubMed PMC
Guaragnella N, Coyne LP, Chen XJ, Giannattasio S. Mitochondria-cytosol-nucleus crosstalk: learning from PubMed PMC
Jazwinski SM. The retrograde response: a conserved compensatory reaction to damage from within and from without. Prog Mol Biol Transl Sci. 2014;127:133–54. PubMed PMC
Liu Z, Butow RA. Mitochondrial retrograde signaling. Annu Rev Genet. 2006;40:159–85. PubMed
Green DR. Cell death: revisiting the roads to ruin. Dev Cell. 2024;59:2523–31. PubMed PMC
Eroglu M, Derry WB. Your neighbours matter—non-autonomous control of apoptosis in development and disease. Cell Death Differ. 2016;23:1110–8. PubMed PMC
Palkova Z, Forstova J. Yeast colonies synchronise their growth and development. J Cell Sci. 2000;113:1923–8. PubMed
Ricicova M, Kucerova H, Vachova L, Palkova Z. Association of putative ammonium exporters Ato with detergent-resistant compartments of plasma membrane during yeast colony development: pH affects Ato1p localisation in patches. Biochim Biophys Acta. 2007;1768:1170–8. PubMed
Santos J, Leao C, Sousa MJ. Ammonium-dependent shortening of CLS in yeast cells starved for essential amino acids is determined by the specific amino acid deprived, through different signaling pathways. Oxid Med Cell Longev. 2013;2013:161986. PubMed PMC
Santos J, Sousa MJ, Leao C. Ammonium is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan. PLoS One. 2012;7:e37090. PubMed PMC
Piccirillo S, Kapros T, Honigberg SM. Phenotypic plasticity within yeast colonies: differential partitioning of cell fates. Curr Genet. 2016;62:467–73. PubMed PMC
Piccirillo S, McCune AH, Dedert SR, Kempf CG, Jimenez B, Solst SR, et al. How boundaries form: Linked nonautonomous feedback loops regulate pattern formation in yeast colonies. Genetics. 2019;213:1373–86. PubMed PMC
Piccirillo S, Morales R, White MG, Smith K, Kapros T, Honigberg SM. Cell differentiation and spatial organization in yeast colonies: Role of cell-wall integrity pathway. Genetics. 2015;201:1427–38. PubMed PMC
Piccirillo S, White MG, Murphy JC, Law DJ, Honigberg SM. The Rim101p/PacC pathway and alkaline pH regulate pattern formation in yeast colonies. Genetics. 2010;184:707–16. PubMed PMC
Kaiser D, Robinson M, Kroos L. PubMed PMC
Shimkets LJ. Social and developmental biology of the myxobacteria. Microbiol Rev. 1990;54:473–501. PubMed PMC
Nariya H, Inouye M. MazF, an mRNA interferase, mediates programmed cell death during multicellular PubMed
Wireman JW, Dworkin M. Developmentally induced autolysis during fruiting body formation by PubMed PMC
Bretl DJ, Kirby JR. Molecular mechanisms of signaling in PubMed
Kroos L. Highly Signal-responsive gene regulatory network governing PubMed PMC
Mercier R, Mignot T. Regulations governing the multicellular lifestyle of PubMed
Janssen GR, Dworkin M. Cell-cell interactions in developmental lysis of PubMed
Popp PF, Mascher T. Coordinated cell death in isogenic bacterial populations: Sacrificing some for the benefit of many? J Mol Biol. 2019;431:4656–69. PubMed
Gelvan I, Varon M, Rosenberg E. Cell-density-dependent killing of PubMed PMC
Varon M, Cohen S, Rosenberg E. Autocides produced by PubMed PMC
Boynton TO, McMurry JL, Shimkets LJ. Characterization of PubMed PMC
Miguelez EM, Hardisson C, Manzanal MB. Hyphal death during colony development in PubMed PMC
Claessen D, Rozen DE, Kuipers OP, Sogaard-Andersen L, van Wezel GP. Bacterial solutions to multicellularity: a tale of biofilms, filaments and fruiting bodies. Nat Rev Microbiol. 2014;12:115–24. PubMed
Mendez C, Brana AF, Manzanal MB, Hardisson C. Role of substrate mycelium in colony development in PubMed
Manteca A, Mader U, Connolly BA, Sanchez J. A proteomic analysis of PubMed
Filippova SN, Vinogradova KA. Programmed cell death as one of the stages of streptomycete differentiation. Microbiology. 2017;86:439–54.
Yague P, Lopez-Garcia MT, Rioseras B, Sanchez J, Manteca A. New insights on the development of PubMed PMC
Panlilio H, Rice CV. The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms. Biotechnol Bioeng. 2021;118:2129–41. PubMed PMC
Pujol C, Daniels KJ, Soll DR. Comparison of switching and biofilm formation between MTL-homozygous strains of PubMed PMC
Soll DR, Daniels KJ. Plasticity of PubMed PMC
Wilking JN, Zaburdaev V, De Volder M, Losick R, Brenner MP, Weitz DA. Liquid transport facilitated by channels in PubMed PMC
Zarnowski R, Westler WM, Lacmbouh GA, Marita JM, Bothe JR, Bernhardt J, et al. Novel entries in a fungal biofilm matrix encyclopedia. mBio. 2014;5:e01333–01314. PubMed PMC
Sarkar S. Release mechanisms and molecular interactions of PubMed
Secchi E, Savorana G, Vitale A, Eberl L, Stocker R, Rusconi R. The structural role of bacterial eDNA in the formation of biofilm streamers. Proc Natl Acad Sci USA. 2022;119:e2113723119. PubMed PMC
Campoccia D, Montanaro L, Arciola CR. Tracing the origins of extracellular DNA in bacterial biofilms: story of death and predation to community benefit. Biofouling. 2021;37:1022–39. PubMed
Gancedo C, Flores CL, Gancedo JM. The expanding landscape of moonlighting proteins in yeasts. Microbiol Mol Biol Rev. 2016;80:765–77. PubMed PMC
Satala D, Karkowska-Kuleta J, Zelazna A, Rapala-Kozik M, Kozik A. Moonlighting proteins at the Candidal cell surface. Microorganisms. 2020;8:1046. PubMed PMC
Nunez-Beltran A, Lopez-Romero E, Cuellar-Cruz M. Identification of proteins involved in the adhesion of PubMed
Silva RC, Padovan AC, Pimenta DC, Ferreira RC, da Silva CV, Briones MR. Extracellular enolase of PubMed PMC
Jarros IC, Veiga FF, Correa JL, Barros ILE, Gadelha MC, Voidaleski MF, et al. Microbiological and virulence aspects of PubMed PMC
Kasai M, Francesconi A, Petraitiene R, Petraitis V, Kelaher AM, Kim HS, et al. Use of quantitative real-time PCR to study the kinetics of extracellular DNA released from PubMed PMC
Martins M, Uppuluri P, Thomas DP, Cleary IA, Henriques M, Lopez-Ribot JL, et al. Presence of extracellular DNA in the PubMed PMC
Bose JL, Lehman MK, Fey PD, Bayles KW. Contribution of the PubMed PMC
Jung CJ, Hsu RB, Shun CT, Hsu CC, Chia JS. AtlA mediates extracellular DNA release, which contributes to PubMed PMC
Nagasawa R, Yamamoto T, Utada AS, Nomura N, Obana N. Competence-stimulating-peptide-dependent localized cell death and extracellular DNA production in PubMed PMC
Qin Z, Ou Y, Yang L, Zhu Y, Tolker-Nielsen T, Molin S, et al. Role of autolysin-mediated DNA release in biofilm formation of PubMed
Thomas VC, Hiromasa Y, Harms N, Thurlow L, Tomich J, Hancock LE. A fratricidal mechanism is responsible for eDNA release and contributes to biofilm development of PubMed PMC
Zeng X, Zou Y, Zheng J, Qiu S, Liu L, Wei C. Quorum sensing-mediated microbial interactions: Mechanisms, applications, challenges and perspectives. Microbiol Res. 2023;273:127414. PubMed
Hazan R, Que YA, Maura D, Strobel B, Majcherczyk PA, Hopper LR, et al. Auto Poisoning of the respiratory chain by a quorum-sensing-regulated molecule favors biofilm formation and antibiotic tolerance. Curr Biol. 2016;26:195–206. PubMed PMC
Van Ark G, Berden JA. Binding of HQNO to beef-heart sub-mitochondrial particles. Biochim Biophys Acta. 1977;459:119–27. PubMed
Armstrong JS. The role of the mitochondrial permeability transition in cell death. Mitochondrion. 2006;6:225–34. PubMed
Quarato G, Llambi F, Guy CS, Min J, Actis M, Sun H, et al. Ca(2+)-mediated mitochondrial inner membrane permeabilization induces cell death independently of Bax and Bak. Cell Death Differ. 2022;29:1318–34. PubMed PMC
Camarillo-Marquez O, Cordova-Alcantara IM, Hernandez-Rodriguez CH, Garcia-Perez BE, Martinez-Rivera MA, Rodriguez-Tovar AV. Antagonistic interaction of PubMed PMC
Vila T, Kong EF, Montelongo-Jauregui D, Van Dijck P, Shetty AC, McCracken C, et al. Therapeutic implications of PubMed PMC
Groicher KH, Firek BA, Fujimoto DF, Bayles KW. The PubMed PMC
Rice KC, Bayles KW. Molecular control of bacterial death and lysis. Microbiol Mol Biol Rev. 2008;72:85–109. PubMed PMC
Endres JL, Chaudhari SS, Zhang X, Prahlad J, Wang SQ, Foley LA, et al. The PubMed PMC
Asally M, Kittisopikul M, Rue P, Du Y, Hu Z, Cagatay T, et al. Localized cell death focuses mechanical forces during 3D patterning in a biofilm. Proc Natl Acad Sci USA. 2012;109:18891–6. PubMed PMC
Mai-Prochnow A, Evans F, Dalisay-Saludes D, Stelzer S, Egan S, James S, et al. Biofilm development and cell death in the marine bacterium PubMed PMC
Webb JS, Thompson LS, James S, Charlton T, Tolker-Nielsen T, Koch B, et al. Cell death in PubMed PMC
Vlamakis H, Aguilar C, Losick R, Kolter R. Control of cell fate by the formation of an architecturally complex bacterial community. Genes Dev. 2008;22:945–53. PubMed PMC
Stovicek V, Vachova L, Palkova Z. Yeast biofilm colony as an orchestrated multicellular organism. Commun Integr Biol. 2012;5:203–5. PubMed PMC
Guilhen C, Forestier C, Balestrino D. Biofilm dispersal: multiple elaborate strategies for dissemination of bacteria with unique properties. Mol Microbiol. 2017;105:188–210. PubMed
Ma L, Conover M, Lu H, Parsek MR, Bayles K, Wozniak DJ. Assembly and development of the PubMed PMC
Rossmann FS, Racek T, Wobser D, Puchalka J, Rabener EM, Reiger M, et al. Phage-mediated dispersal of biofilm and distribution of bacterial virulence genes is induced by quorum sensing. PLoS Pathog. 2015;11:e1004653. PubMed PMC
Uppuluri P, Chaturvedi AK, Srinivasan A, Banerjee M, Ramasubramaniam AK, Kohler JR, et al. Dispersion as an important step in the PubMed PMC
Wall G, Montelongo-Jauregui D, Vidal Bonifacio B, Lopez-Ribot JL, Uppuluri P. PubMed PMC
Engelberg D, Mimran A, Martinetto H, Otto J, Simchen G, Karin M, et al. Multicellular stalk-like structures in PubMed PMC
Scherz R, Shinder V, Engelberg D. Anatomical analysis of PubMed PMC