Reversible acetylation of ribosomal protein S1 serves as a smart switch for Salmonella to rapidly adapt to host stress.

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.