Protein FOG at the interface between G streptococci and human host defence lines

Abstract: Group G streptococci (GGS) may be of four different species and may infect humans and also animals. S. dysgalactiae equisimilis most commonly cause human GGS infections. These bacteria are part of the normal flora, but can cause pharyngitis, erysipelas and impetigo. In the immunocompromised host severe conditions, such as sepsis and necrotising fasciitis, may develop. In this thesis the interactions between GGS and various parts of human defence lines are investigated. A novel M protein from GGS, denoted FOG, was isolated, recombinantly expressed, and purified. FOG-positive strains survive in human whole blood wheras a FOG-negative strain did not. Addition of soluble FOG, but not protein G, leads to restoration of survival of the FOG-negative strain. Intact protein FOG mediated aggregation of neutrophils in the presence of fibrinogen which disabled these cells in excerting antibacterial activities. In vitro and in vivo, protein FOG interacts with collagen I, an abundant extracellular matrix protein of human skin. As streptococcal skin infections often preceed invasive disease, the FOG mediated binding to collagen is important and may be the first step of infection. A FOG-positive strain exhibited adhesional advantages compared to a FOG-negative strain. FOG, like protein G, recruits IgG from human plasma in a non-immune fashion. C1q, initiator of the classical pathway of complement, binds exclusively to the IgG bound via FOG but not to the IgG bound via protein G. IgG opsonisation via FOG but not via protein G led to an O2- production by neutrophils. FOG is released from the bacterial surface into the growth medium of bacterial early stationary growth phase and also by neutrophil elastase. Like M1, an M protein of GAS, FOG binds to monocytes and triggers secretion of the chemokines MIG (CXCL9) and IL-8 (CXCL-8). GGS are less susceptible than GAS, to antimicrobial effects of MIG in physiological NaCl concentrations corresponding to that of sweat and plasma but not of saliva, and also to these NaCl concentrations alone.