Studies of interactions with Streptococcus equi and the host

Streptococcus equi subspecies equi (S. equi) causes strangles, a highly contagious and serious disease in the upper respiratory tract of horses, with a worldwide distribution. Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) is regarded as an opportunistic pathogen infecting horses and other animals, and is believed to be the ancestor of S. equi. Pathogenic bacteria have evolved excellent ways of escaping the immune system and other defence mechanisms or have adapted to efficiently colonise specific areas of the host. The overall objective of this thesis was to study the interaction between S. equi and S. zooepidemicus and the host. An important feature for establishment of an infection and survival of the microorganism inside the host is the interaction with, and adherence to, host tissues. In one of the studies, a group of extracellular proteins with sequence similarities with the fibronectin- and collagen-binding protein FNE, were identified and characterised. All of the proteins bound to collagen to different degrees, and one of the proteins, FNEE, was shown to bind both collagen and fibronectin, and mediate a collagen contraction in presence of PDGF-BB. In another study, an additional IgG endopeptidase of S. equi (and S. zooepidemicus), called IdeE2 (IdeZ2) was described. IdeE2 efficiently degrades horse IgG4, and together with another endopeptidase, this enzyme induced protection in a mouse infection model. In a continuation of the IdeE2/IdeZ2 study, on screening a panel of S. zooepidemicus isolates, sequence variation within the ideZ2 gene was discovered, resulting in three major gene variations. However, the variation in this gene did not reflect the origin of the isolates or the MLST group of the strain. Extended computer alignment with IdeS from S. pyogenes, revealed similarities to structures known to be important for endopeptidase activity. The recombinant proteins IdeZ212, IdeZ216 and IdeZ221 all degraded horse IgG highly efficient despite amino acid differences in between the proteins, which argues for the importance of these proteins in the infection process