Staphylococcus aureus Subvert Autophagy for Induction of Caspase-independent Host Cell Death*
Journal - Journal of Biological Chemistry
Staphylococcus aureus is a common bacterial etiology of seriousinfectious diseases. S. aureus can invade various types of non-professionalphagocytes to produce host cell death. We show here that shortlyafter invasion of HeLa cells S. aureus transit to autophagosomeswas characterized by double membranes and co-localization withLC3. S. aureus were not able to replicate and produce cell deathin autophagy-deficient atg5-/- mouse embryonic fibroblasts.S. aureus-containing autophagosomes do not acidify nor do theyacquire lysosome-associated membrane protein-2, indicating thatS. aureus inhibits autophagosome maturation and fusion withlysosomes. Eventually, S. aureus escape from autophagosomesinto the cytoplasm, which results in caspase-independent hostcell death. S. aureus strains deficient for agr, a global regulatorof S. aureus virulence, were not targeted by autophagy and didnot produce host-cell death. Autophagy induction by rapamycinrestored both replication and cytotoxicity of agr-deficientS. aureus strains, indicating that an agr-regulated factor(s)is required for autophagy-mediated cytotoxicity. The resultsof this study suggest that rapid induction of autophagy is essentialfor S. aureus replication, escape into the cytoplasm, and hostcell killing.* This work was supported by the Deutsche ForschungsgemeinschafGrant SFB 670. The costs of publication of this article weredefrayed in part by the payment of page charges. This articlemust therefore be hereby marked "advertisement" in accordancewith 18 U.S.C. Section 1734 solely to indicate this fact.