Shen Yi-Lin, Liu Tian-Xian, Xu Lei, Ye Bang-Ce, Zhou Ying
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Nucleic Acids Res. 2025 Mar 20;53(6). doi: 10.1093/nar/gkaf252.
Reprogramming metabolic pathways is crucial for pathogens survival in the lethal environments. Here, we present a mechanism by which Salmonella can rapidly respond to the external environment at the translational level; namely, the dynamic acetylation changes at the K247 site of ribosomal protein S1 could modulate the different mRNAs translation to adapt to distinct infection stages. We uncovered that S1K247 preferentially recruits mRNAs associated with flagellum assembly, sulfur metabolism, and SPI-1 T3SS. Conversely, S1K247Ac catalyzed by Pat favors the mRNAs linked to arginine biosynthesis, contributing to the activation of ArgR regulating SPI-2 virulence factors and enabling survival and replication within macrophages. Notably, a K247 acetyl-mimetic mutant strain exhibited increased virulence both ex vivo and in vivo. This mechanism not only aids in further understanding how the pathogen survives in complex environment but also facilitates in identifying new targets and pathways to eliminating pathogenic bacteria.
重编程代谢途径对于病原体在致死环境中的生存至关重要。在此，我们提出了一种机制，通过该机制沙门氏菌能够在翻译水平上快速响应外部环境；即核糖体蛋白S1的K247位点的动态乙酰化变化可以调节不同mRNA的翻译，以适应不同的感染阶段。我们发现S1K247优先招募与鞭毛组装、硫代谢和SPI-1 III型分泌系统相关的mRNA。相反，由Pat催化的S1K247Ac有利于与精氨酸生物合成相关的mRNA，有助于激活调节SPI-2毒力因子的ArgR，并使沙门氏菌能够在巨噬细胞内存活和复制。值得注意的是，一种K247乙酰模拟突变菌株在体外和体内均表现出毒力增加。这种机制不仅有助于进一步了解病原体如何在复杂环境中生存，还便于识别消除病原菌的新靶点和途径。
