Bioinformatics analysis of type II toxin–antitoxin systems and regulatory functional assessment of HigBA and SS-ATA in Streptococcus suis

Toxin–antitoxin (TA) systems, which are prevalent in bacteria and archaea, play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation. Despite the extensive characterization of numerous TA systems in various bacteria, the investigation of these systems within Streptococcus suis is still limited. Here, we systematically analyzed the type II TA systems of 95 S. suis genomes available in the GenBank database using TAfinder. A total of 612 putative type II TA systems were retrieved and classified into 10 categories by phylogenetic analysis. Notably, an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2, 4, 5, 9, 14, Chz, NCL1, and NCL3 strains. The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type VII secretion system in S. suis by measuring β-galactosidase activity and transcriptional changes. Moreover, we unveiled a hitherto uncharacterized, highly prevalent novel TA system, with the composition of antitoxin–toxin–antitoxin (SS-ATA), which regulates the downstream two-component signaling system. Altogether, this study systematically analyzed the type II TA systems within S. suis, highlighting the widespread distribution of HigBA and SS-ATA as important regulatory elements in S. suis.