Swarthmore College, Swarthmore, PA, United States.
University of Houston, Houston, TX, United States.
Adv Appl Microbiol. 2018;102:1-36. doi: 10.1016/bs.aambs.2017.10.001. Epub 2017 Nov 8.
Since the initial discovery of universal stress protein A (UspA) 25 years ago, remarkable advances in molecular and biochemical technologies have revolutionized our understanding of biology. Many studies using these technologies have focused on characterization of the uspA gene and Usp-type proteins. These studies have identified the conservation of Usp-like proteins across bacteria, archaea, plants, and even some invertebrate animals. Regulation of these proteins under diverse stresses has been associated with different stress-response genes including spoT and relA in the stringent response and the dosR two-component signaling pathways. These and other foundational studies suggest Usps serve regulatory and protective roles to enable adaptation and survival under external stresses. Despite these foundational studies, many bacterial species have multiple paralogs of genes encoding these proteins and ablation of the genes does not provide a distinct phenotype. This outcome has limited our understanding of the biochemical functions of these proteins. Here, we summarize the current knowledge of Usps in general and UspA in particular across different genera as well as conclusions about their functions from seminal studies in diverse organisms. Our objective has been to organize the foundational studies in this field to identify the significant impediments to further understanding of Usp functions at the molecular level. We propose ideas and experimental approaches that may overcome these impediments and drive future development of molecular approaches to understand and target Usps as central regulators of stress adaptation and survival. Despite the fact that the full functions of Usps are still not known, creative many applications have already been proposed, tested, and used. The complementary approaches of basic research and applications, along with new technology and analytic tools, may yield the elusive yet critical functions of universal stress proteins in diverse systems.
自 25 年前首次发现普遍应激蛋白 A（UspA）以来，分子和生化技术的显著进步彻底改变了我们对生物学的理解。许多使用这些技术的研究都集中在 uspA 基因和 Usp 型蛋白的特性描述上。这些研究已经确定了 Usp 样蛋白在细菌、古菌、植物，甚至一些无脊椎动物中的保守性。这些蛋白在不同应激下的调控与不同的应激响应基因有关，包括严格反应中的 spoT 和 relA 以及 dosR 双组分信号通路。这些和其他基础研究表明，Usps 发挥调节和保护作用，使生物体能够在外部应激下适应和生存。尽管有这些基础研究，但许多细菌物种都有多个基因编码这些蛋白的同源基因，并且这些基因的缺失并不能提供明显的表型。这一结果限制了我们对这些蛋白生化功能的理解。在这里，我们总结了不同属中普遍应激蛋白（特别是 UspA）的现有知识，并从不同生物体的开创性研究中得出了关于它们功能的结论。我们的目的是组织该领域的基础研究，以确定在分子水平上进一步了解 Usp 功能的重大障碍。我们提出了一些想法和实验方法，这些方法可能克服这些障碍，并推动未来发展分子方法，以了解和靶向 Usps 作为应激适应和生存的中心调节剂。尽管 Usps 的全部功能仍不为人知，但已经提出、测试和使用了许多创造性的应用。基础研究和应用的互补方法，以及新技术和分析工具，可能会揭示普遍应激蛋白在不同系统中的难以捉摸但至关重要的功能。
