A two-component system regulating suilysin production in ST1 serotype 2 Streptococcus suis

Streptococcus suis is a major zoonotic bacterial pathogen that poses significant challenges to both the swine industry and human health. Suilysin, a secreted cytotoxin produced by S. suis, is a critical virulence factor that facilitates bacterial invasion, dissemination, and disruption of the blood-brain barrier. However, the regulation of suilysin production remains incompletely understood. This study demonstrates that the Ihk/Irr two-component system regulates suilysin expression in highly virulent ST1 serotype 2 S. suis strains. Deletion of the ihk and irr genes resulted in significant reductions in suilysin transcript levels and protein abundance. Furthermore, loss of the Ihk/Irr system decreased bacterial cytotoxicity to a level comparable to that observed in a suilysin deletion mutant. Genome-wide transcriptomic analysis revealed that, in addition to suilysin, this two-component system regulates a broad array of genes, including those encoding transcriptional regulators, ABC transporters, and putative virulence factors such as the surface antigen Sao and the cell wall endopeptidase PepO. Overall, this work identifies new regulatory targets of the Ihk/Irr system in S. suis, providing deeper insight into how this pathogen coordinates the expression of its virulence factors.