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

大规模细胞外基质结构和组织样形态发生作为细菌多细胞性的新兴特性

• 批准号: 504035721
• 负责人: Professorin Dr. Regine Hengge
• 金额: --
• 依托单位: Arbeitsgruppe Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/504035721?language=en
• 关键词: Large; scale; extracellular; matrix; architecture

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.

该项目的目的是利用大肠杆菌彻底了解细菌多细胞性的关键结构、功能和调控特性。大肠杆菌大菌落生物膜作为模型系统。这些细胞外基质（ECM）包埋的多细胞细菌聚集体通过产生初级和次级代谢梯度并与之反应而显示出结构时空自组织，从而将其转化为空间上不同的，可再现的三维ECM架构，2个数量级大于数百万个细胞，协调建设它。在广泛的先前和初步的工作，我们已经证明，ECM组成和特定的结构是这种多细胞细菌生命形式的新兴特性的先决条件。这些性质包括（i）非常平坦的大菌落的弹性组织样屈曲和折叠成脊或皱纹的图案而不断裂，即宏观形态发生;（ii）在细胞外但生物膜内部空间中的稳态和“生态位构建”的潜力;以及（iii）保护免受微生物捕食者的侵害。由于后两种性质减少了生物膜群体内的维持能量，因此代表了适应性增益，ECM相关的多细胞性可以被认为是生命本身的一种新兴性质。在此基础上，拟议的项目将追求以下目标：·在分子水平上了解生物膜内部大规模ECM结构的形成及其独特的3D模式，以及它如何与大菌落生物膜的宏观形态发生相关;·检测和证明大规模代谢和调节梯度的形成和关键分子功能·为了阐明允许大规模ECM结构的进化可塑性的遗传调节重新布线及其对宏观形态发生的后果，如用益生菌E. coli Nissle 1917和致病性肠聚集性E.大肠杆菌（EAEC）;·鉴定可能编码转运蛋白的基因，所述转运蛋白参与在生物膜空间内产生“扩展生理学”和稳态;大肠杆菌对捕食者（黄色粘球菌）的抗性。结果和见解，从这项研究中获得的遗传高度听话的模式生物E。大肠杆菌将是理解从细菌和其他微生物的单细胞状态到早期功能性多细胞的进化转变的基础。无论是在概念上还是通过直接的实验合作，该项目都将在SPP 2389中发挥关键的综合作用。