Staphylococcus aureus subvert autophagy for induction of caspase-independent host cell death

被引:228
作者
Schnaith, Annabelle
Kashkar, Hamid
Leggio, Sonja A.
Addicks, Klaus
Kroenke, Martin
Krut, Oleg
机构
[1] Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50935 Cologne, Germany
[2] Univ Cologne, Ctr Mol Med Cologne, D-50935 Cologne, Germany
[3] Univ Cologne, Dept Anat, D-50935 Cologne, Germany
关键词
D O I
10.1074/jbc.M609784200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Weshow here that shortly after invasion of HeLa cells S. aureus transit to autophago-somes 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.
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收藏
页码:2695 / 2706
页数:12
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