Hyperthermophiles, living in environments above 80°C and usually coupling with multi-extreme environmental stresses, have drawn great attention due to their application potential in biotechnology and being the primitive extant forms of life. Studies on their survival and adaptation mechanisms have extended our understanding on how lives thrive under extreme conditions. During these studies, the “cross-stress” behavior in various organisms has been observed between the extreme high temperature and other environmental stresses. Despite the broad observation, the global view of the cross-stress behavior remains unclear in hyperthermophiles, leaving a knowledge gap in our understanding of extreme adaptation. In this study, we performed a global quantitative proteomic analysis under extreme temperatures, pH, hydrostatic pressure (HP), and salinity on an archaeal strain, Thermococcus eurythermalis A501, which has outstanding growth capability on a wide range of temperatures (50–100°C), pH (4–9), and HPs (0.1–70 MPa), but a narrow range of NaCl (1.0–5.0 %, w/v). The proteomic analysis (79.8% genome coverage) demonstrated that approximately 61.5% of the significant differentially expressed proteins (DEPs) responded to multiple stresses. The responses to most of the tested stresses were closely correlated, except the responses to high salinity and low temperature. The top three enriched universal responding processes include the biosynthesis and protection of macromolecules, biosynthesis and metabolism of amino acids, ion transport, and binding activities. In addition, this study also revealed that the specific dual-stress responding processes, such as the membrane lipids for both cold and HP stresses and the signal transduction for both hyperosmotic and heat stresses, as well as the sodium-dependent energetic processes might be the limiting factor of the growth range in salinity. The present study is the first to examine the global cross-stress responses in a piezophilic hyperthermophile at the proteomic level. Our findings provide direct evidences of the cross-stress adaptation strategy (33.5% of coding-genes) to multiple stresses and highlight the specific and unique responding processes (0.22–0.63% of coding genes for each) to extreme temperature, pH, salinity, and pressure, which are highly relevant to the fields of evolutionary biology as well as next generation industrial biotechnology (NGIB).

生活在80°C以上的环境中的高温嗜热菌通常伴随着多种极端的环境压力，由于它们在生物技术中的应用潜力而成为人们的原始生命形式，因而引起了极大的关注。关于它们的生存和适应机制的研究扩展了我们对极端条件下的生活繁荣的理解。在这些研究中，已观察到极端高温和其他环境压力之间各种生物的“交叉压力”行为。尽管有广泛的观察，但是在超嗜热菌中对交叉压力行为的全局看法仍然不清楚，这在我们对极端适应的理解上还存在知识鸿沟。在这项研究中，我们在极端温度，pH，静水压（HP），嗜热球菌A501在各种温度（50–100°C），pH（4–9）和HPs（0.1–70 MPa）范围内均具有出色的生长能力，但NaCl（1.0–5.0％，w / v）。蛋白质组学分析（79.8％的基因组覆盖率）表明，大约61.5％的显着差异表达的蛋白质（DEPs）对多种压力有反应。除对高盐度和低温的响应外，对大多数测试应力的响应密切相关。排名前三位的普遍响应过程包括大分子的生物合成和保护，氨基酸的生物合成和代谢，离子转运和结合活性。此外，这项研究还揭示了特定的双重压力反应过程，例如冷和高压胁迫下的膜脂以及高渗和热胁迫下的信号转导，以及钠依赖性能量过程可能是盐度增长范围的限制因素。本研究是第一个在蛋白质组学水平上检查亲脂性超嗜热菌中的整体交叉应激反应的研究。我们的发现为交叉压力适应策略（占编码基因的33.5％）对多种胁迫的直接提供了直接证据，并强调了针对极端温度，pH，盐度，特定温度和温度的特定且独特的响应过程（每种编码基因的0.22-0.63％）。和压力，这与进化生物学以及下一代工业生物技术（NGIB）高度相关。以及依赖钠的能量过程可能是盐度增长范围的限制因素。本研究是第一个在蛋白质组学水平上检查亲脂性超嗜热菌中的整体交叉应激反应的研究。我们的发现为交叉压力适应策略（占编码基因的33.5％）对多种胁迫的直接提供了直接证据，并强调了针对极端温度，pH，盐度，特定温度和温度的特定且独特的响应过程（每种编码基因的0.22-0.63％）。和压力，这与进化生物学以及下一代工业生物技术（NGIB）高度相关。以及依赖钠的能量过程可能是盐度增长范围的限制因素。本研究是第一个在蛋白质组学水平上检查亲脂性超嗜热菌中的整体交叉应激反应的研究。我们的发现为交叉压力适应策略（占编码基因的33.5％）对多种胁迫的直接提供了直接证据，并强调了针对极端温度，pH，盐度，特定温度和温度的特定且独特的响应过程（每种编码基因的0.22-0.63％）。和压力，这与进化生物学以及下一代工业生物技术（NGIB）高度相关。