FIG 6.

A hypothetical model of the mechanism of LAP induction and autophagy inhibition during GAS infection in endothelial cells. GAS virulence factor SLO activates β1 integrin, followed by NOX2 activation and ROS production for LAP formation, which show insufficient acidification and benefits for GAS multiplication. Simultaneously, NOX2/ROS inhibits autophagy induction, which enhances bacterial clearance and is demonstrated by mTORC1 inactivation and ULK1 recruitment, via activating the PI3K/AKT and MEK1/2/ERK1/2 pathways. These mechanisms provide the strategy for GAS to escape autophagic clearance and to efficiently multiply in endothelial cells.