Large-scale extracellular matrix architecture and tissue-like morphogenesis as emerging properties of bacterial multicellularity

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The proposed project aims at thoroughly understanding key architectural, functional and regulatory properties that emerge from bacterial multicellularity using E. coli macrocolony biofilms as a model system. These extracellular matrix (ECM)-embedded multicellular bacterial aggregates show structural spatio-temporal self-organisation by generating and reacting to primary and secondary metabolic gradients, which thereby are translated into a spatially distinct, reproducible three-dimensional ECM architecture that is >2 orders of magnitude larger than the millions of cells that coordinately build it. In extensive previous and preliminary work we have demonstrated that ECM composition and specific architecture are a prerequisite for the emerging properties of this multicellular bacterial life form. These properties include (i) the elastic tissue-like buckling and folding of very flat macrocolonies into patterns of ridges or wrinkles without breakage, i.e. macroscopic morphogenesis; (ii) the potential for homeostasis and ‘niche construction‘ in the extracellular, yet biofilm-internal space; and (iii) protection against microbial predators. As the latter two properties reduce maintenance energy within the biofilm population and thus represent a fitness gain, ECM-associated multicellularity can be considered an emergent property of life itself. On this basis, the proposed project will pursue the following objectives: • To understand at the molecular level the formation of the biofilm-internal large scale ECM architecture with its distinct 3D patterns and how it relates to macroscopic morphogenesis of macrocolony biofilms; • To detect and demonstrate the formation and key molecular function of large-scale metabolic and regulatory gradients (nutrients, O2, fermentation products, c-di-GMP) in the physiological differentiation that underlies the formation of the ECM architecture; • To clarify the genetic-regulatory rewiring that allows for evolutionary plasticity of the large scale ECM architecture and its consequences for macroscopic morphogenesis as observed with the probiotic E. coli Nissle 1917 and pathogenic enteroaggregative E. coli (EAEC); • To identify genes that may encode transport proteins that are involved in generating an ‘extended physiology‘ and homeostasis within the biofilm space; • To Investigate how the ECM and its specific architecture contribute to protection of E. coli against a predator (Myxococcus xanthus). Results and insights obtained from this study with the genetically highly tractable model organism E. coli will be fundamental to understand the evolutionary transition from the single cell state of bacteria and other microbes to early functional multicellularity. Both conceptually and by direct experimental collaborations, this project will play a key integrative role in SPP 2389.