Fucose utilization-associated genes fcsR and fcsK contribute to the colonization of Streptococcus pasteurianus in mice.

Fucose, a sugar abundant in the host environment, is exploited by many bacteria through fucose utilization gene cluster (FUC) to enhance growth and virulence. Streptococcus pasteurianus is an emerging zoonotic pathogen increasingly recognized as a cause of meningitis and bacteremia in both animals and humans worldwide, yet its pathogenic mechanisms remain poorly understood. In this study, we characterized a putative FUC (E8M05_RS09690-E8M05_RS09645) in S. pasteurianus strain WUSP067, which was isolated from the brain of a piglet with meningitis. The predicted proteins encoded by this cluster share high similarity with FUC-associated proteins in S. pneumoniae. We demonstrated that genes E8M05_RS09685-E8M05_RS09645 are co-transcribed as a single operon whose expression is differentially modulated by carbohydrate availability. Specifically, galactose, glucose, and fructose markedly upregulated fcsR (E8M05_RS09690) expression but repressed operon genes, whereas fucose induced operon expression and suppressed fcsR. Although fcsR lies adjacent to the operon, unlike in S. pneumoniae, it does not directly regulate its transcription, suggesting additional regulatory factors are involved. Functional analyses revealed that both fcsR and fcsK (E8M05_RS09685) contribute to S. pasteurianus colonization in mice and are associated with pathological damage in the brain, spleen, and kidneys. Moreover, the FUC is widely distributed among isolates of both pig and human origin, underscoring its evolutionary and pathogenic significance. Collectively, these findings establish that the FUC enhances the virulence of S. pasteurianus and provide new insights into the regulatory mechanisms of FUC in bacteria.