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Listeria monocytogenes ActA-mediated escape from autophagic recognition


Autophagy degrades unnecessary organelles and misfolded protein aggregates1, as well as cytoplasm-invading bacteria2. Nevertheless, the bacteria Listeria monocytogenes efficiently escapes autophagy3,4. We show here that recruitment of the Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial surface disguises the bacteria from autophagic recognition, an activity that is independent of the ability to mediate bacterial motility. L. monocytogenes expressing ActA mutants that lack the ability to recruit the host proteins initially underwent ubiquitylation, followed by recruitment of p62 (also known as SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to mediate protection from ubiquitylation was further demonstrated by generating aggregate-prone GFP–ActA–Q79C and GFP–ActA–170* chimaeras, consisting of GFP (green fluorescent protein), the ActA protein and segments of polyQ5 or Golgi membrane protein GCP170 (ref. 6). GFP–ActA–Q79C and GFP–ActA–170* formed aggregates in the host cell cytoplasm, however, these ActA-containing aggregates were not targeted for association with ubiquitin and p62. Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy.

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Figure 1: L. monocytogenes lacking ActA is a target of autophagy.
Figure 2: The ability of ActA to mediate bacterial intracellular motility is independent from the ability of L. monocytogenes to escape autophagy.
Figure 3: p62 facilitates autophagy of ubiquitylated ΔactA2.
Figure 4: Anti-aggregating properties of ActA for GFP–polyQ.
Figure 5: Anti-aggregation properties of ActA for GFP–170*.


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We thank all members of the Sasakawa laboratory for discussions and technical advice and A. Amend and N. Schlarenko for help with the generation of several ActA mutants. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to M.O. and C.S, the Special Coordination Funds for Promoting Science from the Japan Science and Technology Agency to C.S, and the ERA-NET Pathogenomics Network funded by the German Ministry of Education and Research and the EU to T.H. and T.C.

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C.S. and T.C. conceived the study. Y.Y. and M.O. performed experiments. Y.Y., M.O., C.S. and T.C. analysed data. M.F., K.M., M.H. and I.N. provided technical advice. M.Y. performed electon microscopic analysis. T.Y. and T.I. generated p62-null mouse embryonic fibroblasts. A.K. generated the Q79C plasmid. E.S. generated the GFP-170* plasmid. T.H. and T.C. generated bacterial strains and antibodies. C.S. and T.C. wrote the manuscript.

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Correspondence to Chihiro Sasakawa.

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The authors declare no competing financial interests.

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Yoshikawa, Y., Ogawa, M., Hain, T. et al. Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat Cell Biol 11, 1233–1240 (2009).

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