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年前首次发现通用应激蛋白A（UspA）以来，分子和生化技术的显着进步彻底改变了我们对生物学的理解。使用这些技术的许多研究都集中在uspA基因和Usp型蛋白的表征上。这些研究已经确定了Usp样蛋白在细菌，古细菌，植物乃至某些无脊椎动物中的保存。下不同应力这些蛋白质的调节已与不同应激反应基因，包括相关联的斑点和RELA在严格响应和dosR两部分信号通路。这些和其他基础研究表明，Usps发挥调节和保护作用，以在外部压力下适应和生存。尽管有这些基础的研究，许多细菌种类仍具有编码这些蛋白质的基因的多个旁系同源物，并且这些基因的切除并没有提供独特的表型。这一结果限制了我们对这些蛋白质的生化功能的了解。在这里，我们总结了有关Usps的当前知识，尤其是有关不同属的UspA的最新知识，以及它们在各种生物中的开创性研究中得出的有关功能的结论。我们的目标是组织该领域的基础研究，以识别在分子水平上进一步理解Usp功能的重大障碍。我们提出了可以克服这些障碍的想法和实验方法，并推动了分子方法的未来发展，以将Usps理解为应激适应和生存的中心调节剂。尽管还不清楚Usps的全部功能，但已经提出，测试和使用了许多创新的应用程序。基础研究和应用的补充方法，以及新技术和分析工具，可能会在各种系统中产生通用应激蛋白难以捉摸但至关重要的功能。创造性的许多应用已经被提出，测试和使用。基础研究和应用的补充方法，以及新技术和分析工具，可能会在各种系统中产生通用应激蛋白难以捉摸但至关重要的功能。创造性的许多应用已经被提出，测试和使用。基础研究和应用的补充方法，以及新技术和分析工具，可能会在各种系统中产生通用应激蛋白难以捉摸但至关重要的功能。