Group B Streptococcus virulence factors and vaccine targets
Venue: Edificio Povo 1, via Sommarive nr. 5, Povo (Tn) - Room A107
At 11:00 a.m.
- Immaculada Margarit Y Ros - GSK, Vaccines Research, Siena, Italy
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive microorganism that colonizes the human lower intestinal and genital tracts and can cause life-threatening infections in neonates and in immuno-compromised adults. Maternal vaccines are in development to prevent GBS neonatal infection. The capsular polysaccharide (CPS) is the main vaccine target and a major virulence factor that prevents bacterial killing by phagocytes. During the first part of my presentation, I will describe the use of genome based approaches to investigate the genetic basis of CPS assembly and its impact on GBS evolution. The 20 proteins responsible for GBS capsule synthesis are encoded in the genetically variable cps operon. Ten CPS variants exist, each recognized by specific antibodies and therefore GBS strains are classified into ten serotypes. By deep genome sequencing of a wide panel of natural mutants that do not produce any capsule (Non-typeable, NT), we identified the cps genes that are essential for capsular polysaccharide assembly. We subsequently explored the determinants of CPS antigenic specificity, focusing on the genetic relationship between the chemically related capsular serotypes V, VII and IX. This analysis led to the identification of cpsM, cpsO and cpsI as responsible for the differences in CPS structure between these three serotypes. Chimeric CPS structures incorporating epitopes from the different serotypes could be obtained by heterologous transfer of cps MOI gene variants between strains. Finally, we performed a population-wide genomic analysis of strains belonging to the serotype IV and observed that recombination of a large genomic portion comprising the cps operon led to the emergence of a new phylogenetic lineage that has recently expanded in the GBS population. During the second part of my presentation, I will describe the identification of surface proteins conferring serotype independent protection against GBS infection, and a novel family of GBS secreted virulence factors that modulate host innate immune responses by means of their molecular interaction with the human Complement System.