Staphylococcus aureus escapes endosomes and autophagosomes via α-hemolysin.

The interplay between endosomal and autophagic pathways is crucial for intracellular transport and modulation of pathogen replication. However, the mechanisms underlying the interaction between endosomes and autophagosomes (APs) in the context of Staphylococcus aureus (S. aureus) infection are not well understood. Specifically, the fusion of multivesicular bodies (MVBs) or recycled endosomes (REs) with APs remains unexplored. Here, we reveal that S. aureus induces crosstalk between endosomes and APs, a process modulated by Ca2+ influx. Depletion of Rab11A from REs impairs APs formation and trafficking. Meanwhile, we identify α-hemolysin (α-toxin, Hla) as a key virulence factor in S. aureus-induced membrane damage. α-Hemolysin facilitates S. aureus escape from vesicles, contributing to cytotoxicity and membrane disruption.