The SaeRS two-component system regulates virulence gene expression in group B Streptococcus during invasive infection

• Published in: mBio Vol. 15; no. 9; pp. e0197524 - 24
• Main Authors: Coppolino, Francesco, De Gaetano, Giuseppe Valerio, Claverie, Cosme, Sismeiro, Odile, Varet, Hugo, Legendre, Rachel, Pellegrini, Angelica, Berbiglia, Alessia, Tavella, Luca, Lentini, Germana, Famà, Agata, Barbieri, Giulia, Pietrocola, Giampiero, Teti, Giuseppe, Firon, Arnaud, Beninati, Concetta
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 11.09.2024
• Subjects: Animals; Bacterial Adhesion - genetics; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Disease Models, Animal; Female; Gene Expression Regulation, Bacterial; group B Streptococcus; host colonization; Humans; Life Sciences; Mice; Microbial Genetics; Research Article; Streptococcal Infections - microbiology; Streptococcus agalactiae - genetics; Streptococcus agalactiae - metabolism; Streptococcus agalactiae - pathogenicity; two-component systems; Virulence - genetics; virulence factors; Virulence Factors - genetics; Virulence Factors - metabolism; group B Streptococcus; two-component systems; virulence factors; host colonization
• ISSN: 2150-7511; 2161-2129; 2150-7511
• DOI: 10.1128/mbio.01975-24

Group B (GBS) is a pathobiont responsible for invasive infections in neonates and the elderly. The transition from a commensal to an invasive pathogen relies on the timely regulation of virulence factors. In this study, we characterized the role of the SaeRS two-component system in GBS pathogenesis. Loss-of-function mutations in the SaeR response regulator decrease virulence in mouse models of invasive infection by hindering the ability of bacteria to persist at the inoculation site and to spread to distant organs. Transcriptome and analysis reveal a specialized regulatory system specifically activated during infection to control the expression of only two virulence factors: the PbsP adhesin and the BvaP secreted protein. The surge in SaeRS-regulated genes is complemented by fine-tuning mediated by the repressor of virulence CovRS system to establish a coordinated response. Constitutive activation of the SaeRS regulatory pathway increases PbsP-dependent adhesion and invasion of epithelial and endothelial barriers, though at the cost of reduced virulence. In conclusion, SaeRS is a dynamic, highly specialized regulatory system enabling GBS to express a restricted set of virulence factors that promote invasion of host barriers and allow these bacteria to persist inside the host during lethal infection. Group B (or GBS) is a normal inhabitant of the human gastrointestinal and genital tracts that can also cause deadly infections in newborns and elderly people. The transition from a harmless commensal to a dangerous pathogen relies on the timely expression of bacterial molecules necessary for causing disease. In this study, we characterize the two-component system SaeRS as a key regulator of such virulence factors. Our analysis reveals a specialized regulatory system that is activated only during infection to dynamically adjust the production of two virulence factors involved in interactions with host cells. Overall, our findings highlight the critical role of SaeRS in GBS infections and suggest that targeting this system may be useful for developing new antibacterial drugs.