From the Environment to the Host: Re-Wiring of the Transcriptome of Pseudomonas aeruginosa from 22°C to 37°C

Pseudomonas aeruginosa is a highly versatile opportunistic pathogen capable of colonizing multiple ecological niches. This bacterium is responsible for a wide range of both acute and chronic infections in a variety of hosts. The success of this microorganism relies on its ability to adapt to environmental changes and re-program its regulatory and metabolic networks. The study of P. aeruginosa adaptation to temperature is crucial to understanding the pathogenesis upon infection of its mammalian host. We examined the effects of growth temperature on the transcriptome of the P. aeruginosa PAO1. Microarray analysis of PAO1 grown in Lysogeny broth at mid-exponential phase at 22°C and 37°C revealed that temperature changes are responsible for the differential transcriptional regulation of 6.4% of the genome. Major alterations were observed in bacterial metabolism, replication, and nutrient acquisition. Quorum-sensing and exoproteins secreted by type I, II, and III secretion systems, involved in the adaptation of P. aeruginosa to the mammalian host during infection, were up-regulated at 37°C compared to 22°C. Genes encoding arginine degradation enzymes were highly up-regulated at 22°C, together with the genes involved in the synthesis of pyoverdine. However, genes involved in pyochelin biosynthesis were up-regulated at 37°C. We observed that the changes in expression of P. aeruginosa siderophores correlated to an overall increase in Fe2+ extracellular concentration at 37°C and a peak in Fe3+ extracellular concentration at 22°C. This suggests a distinct change in iron acquisition strategies when the bacterium switches from the external environment to the host. Our work identifies global changes in bacterial metabolism and nutrient acquisition induced by growth at different temperatures. Overall, this study identifies factors that are regulated in genome-wide adaptation processes and discusses how this life-threatening pathogen responds to temperature.

铜绿假单胞菌（Pseudomonas aeruginosa）是一种多功能极强的机会致病菌，可定植于多种生态位。该菌可在多种宿主中引发广泛的急性与慢性感染。其生存与致病的核心优势，在于能够适应环境变化并重编程自身的调控与代谢网络。解析铜绿假单胞菌对温度的适应机制，对于阐明其感染哺乳动物宿主后的致病机理至关重要。我们针对生长温度对铜绿假单胞菌PAO1转录组（transcriptome）的影响展开了研究。对在Lysogeny broth（LB培养基）中于指数生长中期、分别在22℃与37℃条件下培养的PAO1进行微阵列分析（microarray analysis）后发现，温度变化可导致6.4%的基因组发生差异性转录调控。细菌的代谢、复制与营养获取通路均出现了显著改变。群体感应（quorum-sensing）系统以及I型、II型、III型分泌系统所分泌的外分泌蛋白——这些因子参与了铜绿假单胞菌感染宿主时的宿主适配过程——在37℃下的表达量较22℃时显著上调。编码精氨酸降解酶（arginine degradation enzymes）的基因在22℃下表达量大幅上调，同时参与荧光铁载体（pyoverdine）生物合成的基因也同步上调。然而，参与脓杆菌素（pyochelin）生物合成的基因则在37℃下表达上调。我们观察到，铜绿假单胞菌铁载体（siderophores）的表达变化，与37℃下细胞外Fe²+浓度整体升高、22℃下细胞外Fe³+浓度达到峰值的现象高度相关。这表明当细菌从外界环境切换至宿主环境时，其铁获取策略发生了显著分化。本研究揭示了不同生长温度所诱导的细菌代谢与营养获取的全局性转录调控变化。总体而言，本研究明确了全基因组适应过程中受调控的各类关键因子，并探讨了这一致命性病原体如何响应温度信号以完成环境适配。