Pushing the Envelope: Defining a Cytoskeletal-like Protein Required for Spore Development

细胞形状是生物体的一个重要特征，与它们在环境中生存的功能和能力有关。在细菌中，细胞形状的维持是由其外层（称为细胞包膜）的组装和重塑所控制的。已知的抗生素靶向细菌的细胞包膜，影响细菌的细胞形状，导致细菌存活和死亡的减少。因此，了解细菌细胞形状和细胞包膜组装的机制可以为药物开发带来新的机会。在这个项目中，我们专注于一个新的分子过程，控制细菌内生孢子（孢子）的细胞形状和细胞包膜组装，内生孢子是地球上最坚韧的细胞类型之一。孢子是一些细菌产生的具有高度抗性的休眠细胞，可以在饥饿压力下存活。孢子可以在环境中存活很长时间。为了响应营养物质的可用性或其他信号，孢子通过一个称为发芽的过程“重新激活”成正在生长的细菌。孢子具有明确的形状，并具有复杂的多层细胞包膜，这有助于它们的抗性和在环境中的持久性。一些细菌产生的孢子是人类、动物和传粉昆虫反复感染和致命感染的基础。孢子还会污染食物，危害食品安全，导致食物中毒。重要的是，孢子不受当前抗生素的影响，它们抵抗杀死生长细菌的常见灭菌策略。虽然多项研究有助于确定孢子包膜的复杂组成，但对调节孢子形状和孢子包膜组装的分子机制知之甚少，这两者似乎是相互联系的。通过汇集分子遗传学，生物化学，细胞生物学和结构生物学方法的专家团队，该项目期望定义一个新的孢子包膜组装和维持孢子形状所需的分子过程。初步数据表明，这种机制使用了一种蛋白质，其功能可能类似于孢子内部的结构支架，并有助于孢子的形状和重要的孢子包膜层（皮层）的组装。皮层不仅对孢子的抗性有贡献，而且在孢子通过萌发脱离休眠中起着关键作用。该项目的主要预期成果是关于细菌如何转化为孢子的新知识。这一新知识的好处是它将加深和发展我们对细菌孢子以及细菌如何构建高抗性孢子细胞包膜的理解。这些知识可能为生物技术行业探索控制孢子形成细菌的创新策略提供一个平台。该项目还将为下一代微生物学家提供培训，确保英国在微生物学领域的未来，这是一个对动物、人类和环境健康以及食品安全至关重要的领域。

Cell shape is an important feature of living organisms, linked to their function and ability to survive in the environment. In bacteria, the maintenance of cell shape is governed by the assembly and remodelling of their external layers, known as the cell envelope. Known antibiotics target the bacterial cell envelope and affect bacterial cell shape, leading to reduced bacterial survival and death. Thus, understanding the mechanisms underlying bacterial cell shape and cell envelope assembly can lead to new opportunities in drug development. In this project we focus on a new molecular process that controls the cell shape and cell envelope assembly of bacterial endospores (spores), one of the toughest cell types on Earth. Spores are highly-resistant, dormant cells produced by some bacteria to survive starvation stress. Spore can persist in the environment for extended periods of time. In response to nutrient availability, or other signals, spores "reactivate" into growing bacteria through a process called germination. Spores have a defined shape and harbor a complex, multilayered cell envelope that contributes to their resistance properties and persistence in the environment. Some bacteria produce spores that underlie recurring and often deadly infections in humans, animals and pollinator insects. Spores can also contaminate food, compromise food safety and lead to food poisoning. Importantly, spores are not affected by current antibiotics and they resist common sterilisation strategies that kill growing bacteria. While multiple studies have contributed to defining the complex composition of the spore envelope, less is known about the molecular mechanisms that regulate spore shape and the assembly of the spore envelope, which appear to be connected. By bringing together a team of experts in molecular genetics, biochemistry, cell biology and structural biology methods, this project expects to define a novel molecular process required for the assembly of the spore envelope and the maintenance of spore shape. Preliminary data suggest this mechanism employs a protein that may function like a structural scaffold on the inside of the spore and contributes to spore shape and assembly of an important spore envelope layer, the cortex. The cortex not only contributes to spore resistance properties but also plays a critical role in their exit from dormancy through germination. The project's primary expected outcome is new knowledge of how bacteria transform into spores. The benefit of this new knowledge is that it will deepen and grow our understanding of bacterial spores and how bacteria build the highly-resistant spore cell envelope. This knowledge may provide a platform from which biotechnology industries could explore innovative strategies for controlling spore-forming bacteria. This project will also provide training to the next generation of microbiologists, securing Britain's future in Microbiology, a field that is critical to animal, human and environmental health, as well as food safety.