Background: Streptococcus agalactiae or group B streptococci (GBS) cause a range of invasive maternal-fetal diseases during pregnancy and post-partum. However, invasive infections in non-pregnant adults are constantly increasing. These include sepsis and streptococcal toxic shock syndrome, which are often complicated by systemic coagulation and thrombocytopenia. A key factor promoting GBS virulence is the hyper-hemolytic ornithine rhamnolipid pigment toxin associated with the surface.
Methods: Human blood and primary cells were stimulated with pigmented and non-pigmented GBS or pigment itself and blood clotting, cytokine release, and cell functions were assessed.
Results: Not all pigmented GBS harbor covR/S mutations. However, genes encoding for the pigment synthesis pathway are upregulated in pigmented strains without these mutations. Stimulation of human neutrophils, monocytes, and PBMCs with hyper-hemolytic strains and pigment toxin resulted in a release of pro-inflammatory mediators. In addition, LUMC16, a pigmented and highly hemolytic GBS from an STSS case, induced blood clotting and showed factor XII activity on its surface. Infections of human platelets with pigmented GBS as well as stimulations with pigment resulted in an initial platelet activation followed by apoptotic cell death. In contrast, platelets retained the resting phenotype in infections with non-pigmented strains.
Conclusions: Our study shows that the hemolytic lipid toxin contributes to the ability of GBS to cause systemic hyper-inflammation. Furthermore, it interferes with the coagulation system and impairs platelet function in a two-step process.