Group A Streptococcus translocates across an epithelial barrier via degradation of intercellular junctions

Abstract

BackgroundStreptococcus pyogenes (group A Streptococcus, GAS) is a versatile human pathogen associated with a variety of mucosal and invasive diseases. In order to cause severe invasive diseases, GAS must penetrate the host epithelial barrier in the pharynx or damaged skin together with evasion of host defense mechanisms. GAS possesses strategies to overcome the epithelial barrier via paracellular and intracellular routes. Here, we review recent findings to better understand the pathogenesis of GAS infection by a transepithelial process via a paracellular route. HighlightRecently, we reported that streptolysin S, a determinant for β-hemolysis, facilitates bacterial penetration by degrading epithelial intercellular junctions in concert with host proteases. Furthermore, we provided evidence that a broad spectrum secreted cysteine protease, streptococcal pyrogenic exotoxin B (SepB), directly cleaves transmembrane proteins associated with the epithelial barrier to permit GAS to invade deeper into tissues. ConclusionOur investigations of interactions of bacteria with intercellular junctions have provided further insight into the mechanisms used by GAS to disrupt the epithelial barrier. Elucidation of molecular mechanisms underlying the initial stage of GAS infections in these studies may expedite development of novel preventive or therapeutic agents for severe invasive GAS infections.