Abstract
Staphylococcus aureus is a common bacterial etiology of serious infectious diseases. S. aureus can invade various types of non-professional phagocytes to produce host cell death. We show here that shortly after invasion of HeLa cells S. aureus transit to autophagosomes was characterized by double membranes and co-localization with LC3. S. aureus were not able to replicate and produce cell death in autophagy-deficient atg5-/- mouse embryonic fibroblasts. S. aureus-containing autophagosomes do not acidify nor do they acquire lysosome-associated membrane protein-2, indicating that S. aureus inhibits autophagosome maturation and fusion with lysosomes. Eventually, S. aureus escape from autophagosomes into the cytoplasm, which results in caspase-independent host cell death. S. aureus strains deficient for agr, a global regulator of S. aureus virulence, were not targeted by autophagy and did not produce host-cell death. Autophagy induction by rapamycin restored both replication and cytotoxicity of agr-deficient S. aureus strains, indicating that an agr-regulated factor(s) is required for autophagy-mediated cytotoxicity. The results of this study suggest that rapid induction of autophagy is essential for S. aureus replication, escape into the cytoplasm, and host cell killing.
Highlights
We have recently shown that some but not all S. aureus strains are able to induce host cell death after invasion, which correlates with the virulence of a particular S. aureus strain [8]
To investigate the impact of apoptotic machinery in cytotox- containing compartment together with the surrounding cytoicity induced during S. aureus infection, HeLa cells were lysed plasm until double membranes closely enveloped the bacteria at distinct times after infection, and cellular lysates were ana- within 3 h post-infection, which meets the main morphological lyzed by Western blotting for processing/activation of execu- criteria of autophagosomes
We provide evidence that unlike group A Streptococcus, transition into autophagosomes provides a protective niche for intracellular S. aureus, where they survive, replicate, and escape into cytoplasm to eventually kill the eukaryotic host cell
Summary
We have recently shown that some but not all S. aureus strains are able to induce host cell death after invasion, which correlates with the virulence of a particular S. aureus strain [8]. To investigate the impact of apoptotic machinery in cytotox- containing compartment together with the surrounding cytoicity induced during S. aureus infection, HeLa cells were lysed plasm until double membranes closely enveloped the bacteria at distinct times after infection, and cellular lysates were ana- within 3 h post-infection, which meets the main morphological lyzed by Western blotting for processing/activation of execu- criteria of autophagosomes.
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