The orphan response regulator RevSC21 controls the attachment of Streptococcus suis serotype-2 to human laryngeal epithelial cells and the expression of virulence genes.

Streptococcus suis-2 is an important zoonotic pathogen that causes serious diseases such as meningitis, septicemia, endocarditis, arthritis and septic shock in pigs and humans. Little is known about the regulation of virulence gene expression in S. suis-2. In the present study, we characterized an orphan transcriptional regulator, designated RevSC21. The RevSC21 gene was cloned and the sequence was determined. Deletion of the revSC21 gene of S. suis-2 yielded a mutant strain, SC211, which exhibited a significant decrease in adherence to cell line Hep-2, and lacked hemolytic activity. Quantification of expression levels of known S. suis-2 SC21 virulence genes by real-time PCR in vitro and in vivo revealed that RevSC21 influences the expression of mrp, ef, sly, fbps, sod, rpob, gyra hyl, cps and gapdh virulence-associated genes. SC211 was shown to be attenuated in a 50% lethal dose assay and bacteriology, indicating that RevSC21 plays an important part in the pathogenesis of S. suis-2 infection. Mutant SC211 was 100% defective in virulence in CD1 mice at up to 10(7) CFU, and provided 100% protection when challenged with 10(7) CFU of the SC21 strain.