The ABC type fucose operon regulated by XtrSs through CcpA contributes to Streptococcus suis survival in macrophages

Streptococcus suis (S. suis), an important zoonotic pathogen, poses a huge threat to the pig industry and human health. The fucose operon (FCS) is found in many bacteria that utilize host glycosylation modifications, contributing to bacterial growth and infection. We previously discovered that the virulence associated streptococcal transcriptional regulator XtrSs could downregulate FCS transcription. In this study, the FCSs of S. suis were classified into ABC and PTS types, and XtrSs indirectly repressed ABC type FCS transcription. Importantly, we found that Catabolite control protein A (CcpA) was the intermediate regulator of XtrSs, but not the FCS upstream regulator FcsR, directly repressing ABC type FCS transcription by binding to a novel Cre site. Interestingly, although ABC type FCS responded to fucose, S. suis failed to proliferate in media with fucose as the sole carbon source. Notably, FCS mutant treated macrophages exhibited decreased fucosyltransferases transcription and impaired AMPK/mTOR signaling to a certain extent, which resulted in increased autophagy processes and ultimately decreasing S. suis survival in macrophages. In conclusion, our findings first confirmed the detailed regulatory mechanism of ABC type FCS and revealed that FCS contributed to the intramacrophage survival of S. suis by inhibiting autophagy processes.