Streptococcus evades skin autophagy
Streptococcus pyogenes or group A streptococci (GAS) are responsible for hundreds of thousands of superficial as well as life-threatening, invasive infections. To cause invasive infection, GAS must first penetrate the epithelial cells of the skin, which act as a protective barrier to the external world. Under physiological conditions, epithelial cells clear GAS by an engulfing mechanism known as autophagy. Autophagy normally serves to degrade long-living proteins and recycle intracellular organelles in response to starvation. Though autophagy works as an immune response against invasion, GAS can evade autophagy and cause life-threatening infections. Scientists on the EU-funded GASAUTOPHAGY (Influence of Streptococcal virulence factors on host autophagy regulation) project set out to identify novel virulence factors that allow GAS to evade autophagy. In this context, they identified SpyCEP, a GAS serine protease known to inactivate the human interleukin-8. Researchers observed a decreased activation of the host autophagy inhibitor calpain when they down-regulated SpyCEP. The opposite effect was seen upon overexpression of SpyCEP, suggesting that GAS utilised the virulence factor SpyCEP to avoid entrapment into autophagosomes. These observations extended to the zoonotic Group C streptococcus (GCS) and Group G streptococcus (GGS), which are of increasing clinical interest due to their capacity to cause serious infections in humans. The GASAUTOPHAGY research team discovered that GAS, GCS and GGS shared virulence factors that might have passed through horizontal gene transfer. Nonetheless, the skin epithelium could efficiently clear GCS and GGS through an autophagy-mediated mechanism. Collectively, the results of the GASAUTOPHAGY study unveiled a novel streptococcal evasion mechanism critical for host-pathogen interaction. Furthermore, they identified SpyCEP as a possible target for the treatment of invasive streptococcal infections.
Keywords
Streptococcus, autophagy, skin epithelial cells, SpyCEP, calpain
