Institute of Microbiology, Technische Universität Dresden, Dresden, Germany.
Department of Microbiology, The Ohio State Universitygrid.261331.4, Columbus, Ohio, USA.
mSystems. 2022 Jun 28;7(3):e0134821. doi: 10.1128/msystems.01348-21. Epub 2022 May 23.
Maintaining cell envelope integrity is of vital importance for all microorganisms. Not surprisingly, evolution has shaped conserved protein protection networks that connect stress perception, transmembrane signal transduction, and mediation of cellular responses upon cell envelope stress. The phage shock protein (Psp) stress response is one such conserved protection network. Most knowledge about the Psp response derives from studies in the Gram-negative model bacterium Escherichia coli, where the Psp system consists of several well-defined protein components. Homologous systems were identified in representatives of the , , and . However, the Psp system distribution in the microbial world remains largely unknown. By carrying out a large-scale, unbiased comparative genomics analysis, we found components of the Psp system in many bacterial and archaeal phyla and describe that the predicted Psp systems deviate dramatically from the known prototypes. The core proteins PspA and PspC have been integrated into various (often phylum-specifically) conserved protein networks during evolution. Based on protein domain-based and gene neighborhood analyses of and homologs, we built a natural classification system for Psp networks in bacteria and archaea. We validate our approach by performing a comprehensive protein interaction study of Psp domains identified in the Gram-positive model organism Bacillus subtilis and found a strong interconnected protein network. Our study highlights the diversity of Psp domain organizations and potentially diverse functions across the plethora of the microbial landscape, thus laying the ground for studies beyond known Psp functions in underrepresented organisms. The PspA protein domain is found in all domains of life, highlighting its central role in Psp networks. To date, all insights into the core functions of Psp responses derive mainly from protein network blueprints representing only three bacterial phyla. Despite large overlaps in function and regulation, the evolutionary diversity of Psp networks remains largely elusive. Here, we present an unbiased protein domain- and genomic context-centered approach that describes and classifies Psp systems. Our results suggest so-far-unknown Psp-associated roles with other protein networks giving rise to new functions. We demonstrate the applicability of our approach by dissecting the Psp protein network present in Bacillus subtilis and demonstrate Psp domains working in concert with other cell envelope stress response systems. We find that the Psp-like protein universe reflects a surprising diversity within the bacterial and archaeal microbial world.
维持细胞包膜完整性对所有微生物都至关重要。毫不奇怪，进化塑造了保守的蛋白质保护网络，将应激感应、跨膜信号转导和细胞包膜应激后的细胞反应联系起来。噬菌体休克蛋白（Psp）应激反应就是这样一个保守的保护网络。大多数关于 Psp 反应的知识都来自于革兰氏阴性模式细菌大肠杆菌的研究，其中 Psp 系统由几个定义明确的蛋白质成分组成。在 、 和 的代表中鉴定出了同源系统。然而，Psp 系统在微生物世界中的分布在很大程度上仍然未知。通过进行大规模、无偏的比较基因组学分析，我们在许多细菌和古菌门中发现了 Psp 系统的成分，并描述了预测的 Psp 系统与已知原型有很大的不同。核心蛋白 PspA 和 PspC 在进化过程中已经整合到各种（通常是特定于门的）保守蛋白质网络中。基于 和 同源物的基于蛋白质结构域和基因邻居的分析，我们构建了细菌和古菌中 Psp 网络的自然分类系统。我们通过对革兰氏阳性模式生物枯草芽孢杆菌中鉴定出的 Psp 结构域进行全面的 蛋白质相互作用研究，验证了我们的方法，并发现了一个强大的相互关联的蛋白质网络。我们的研究强调了 Psp 结构域组织的多样性和潜在的多样化功能，跨越了微生物景观的多样性，从而为在代表性不足的生物体中研究除了已知的 Psp 功能之外的功能奠定了基础。PspA 蛋白结构域存在于所有生命领域，突出了其在 Psp 网络中的核心作用。迄今为止，所有关于 Psp 反应核心功能的见解主要来自仅代表三个细菌门的蛋白质网络蓝图。尽管功能和调节有很大的重叠，但 Psp 网络的进化多样性在很大程度上仍然难以捉摸。在这里，我们提出了一种无偏的基于蛋白质结构域和基因组上下文的方法，用于描述和分类 Psp 系统。我们的结果表明，迄今为止，与其他蛋白质网络相关的 Psp 相关作用产生了新的功能。我们通过剖析枯草芽孢杆菌中存在的 Psp 蛋白质网络来证明我们方法的适用性，并证明 Psp 结构域与其他细胞包膜应激反应系统协同工作。我们发现，Psp 样蛋白宇宙反映了细菌和古菌微生物世界中令人惊讶的多样性。
