Listeriolysin O is Necessary and Sufficient to Induce Autophagy During Listeria Monocytogenes Infection

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Background: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection. Methodology/Principal Findings: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5-/-). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubuleassociated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3- GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5-/- mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5-/- BMDMs. Conclusions/Significance: We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs.

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Meyer-Morse, N., Robbins, J. R., Rae, C.S., Mochegova, S.N., Swanson, M.S., Zhao, Z., Virgin, H.W., & Portnoy, D. (2010). Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. PLoS ONE, 5(1), e8610.


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