Adhesion and internalization of Streptococcus pyogenes on an epithelial cell layer as visualized by scanning electron microscopy. The scale bar represents 2 μm. Bacteria being internalized are shown at higher magnification in the insert (scale bar 1μm). Photo courtesy of Matthias Mörgelin, Lund University, Sweden.

For many bacterial pathogens, adhesion to host cells and subsequent internalization are the two initial steps in the colonization process. For Streptococcus pyogenes, binding to fibronection via the cell-wall-attached fibronectin-binding receptor, protein F1, is a key molecular interaction that mediates these steps. Now, a report published in the May issue of Microbiology sheds new light on the regulation of this crucial interaction by revealing a role for the secreted bacterial protease, SpeB.

SpeB, which is secreted in large amounts by most S. pyogenes strains, has broad proteolytic activity against a number of different human proteins, as well as several S. pyogenes proteins that are located on the bacterial cell surface. Previous studies have also shown that SpeB contributes to bacterial internalization, but the mechanisms by which the protease influences this process were unclear. Patrik Nyberg and colleagues set out to clarify the role of SpeB in streptococcal entry into host cells, focusing on the requirement of fibronectin. Initially, the authors were able to demonstrate that growing S. pyogenes in a medium that promoted SpeB expression reduced the ability of the bacteria to bind to fibronectin. They were further able to show that this reduction in fibronectin-binding activity was due to the proteolysis of protein F1 by SpeB. As bacterial internalization is mediated by protein F1, the authors were also able to demonstrate that the removal of protein F1 from the bacterial cell surface by SpeB resulted in a significant decrease in adhesion and internalization. Unlike other surface proteins of S. pyogenes that are protected from proteolytic degradation by interacting with their ligands, protein F1 was readily cleaved by SpeB, even when complexed with fibronectin.

These data unambiguously show the sensitivity of the fibronectin-binding activity of S. pyogenes to the proteolytic action of SpeB with the resulting effects on bacterial internalization. This function for SpeB could represent a mechanism for the proteolytic regulation of S. pyogenes entry into host cells. Indeed, as SpeB expression and secretion are thought to be induced when the bacteria are in an environment in which nutrients are limited, the authors speculate that proteolysis of protein F1 and the subsequent inhibition of adhesion and internalization, could promote bacterial dissemination by allowing the movement of S. pyogenes to new and more fertile locations.