The conserved transcription factor PrlP modulates colonization and pathogenicity of Streptococcus suis in response to environmental stress.

Opportunistic pathogens can cause infections when host defenses are compromised. Among them, Streptococcus suis (S. suis) colonizes the upper respiratory tract of pigs and causes severe diseases in both swine and humans. Although the pathogenic mechanisms of these bacteria have been partially elucidated, the molecular processes that govern their adaptation, colonization, and pathogenesis remain incompletely understood. In this study, we identified PrlP as a transcriptional repressor in S. suis that responds to mildly acidic, oxidative, hyperosmotic, and thermal stresses, and regulates bacterial growth, chain morphology, nasal colonization, and virulence. The C-terminal S24 peptidase domain of PrlP mediates stress-induced self-cleavage to control protein stability, while the N-terminal helix-turn-helix (HTH) DNA-binding domain is essential for its transcriptional regulatory function. Combined ChIP-seq and RNA-seq analyses revealed its binding motif (5'-CCTGAAWCT-3') and identified B9H01_08740 as a direct target gene, as further validated by EMSA. Notably, deletion of B9H01_08740 in the prlP-deficient background restored the associated phenotypes. These findings highlight PrlP as a key regulator in S. suis that maintains cellular homeostasis in response to stress conditions and modulates target genes such as B9H01_08740 to promote nasal colonization and virulence. Therefore, this study provides new insights into the regulatory mechanisms of pathogenic bacteria and may aid in the development of targeted strategies against S. suis infections.