PMID- 20062534
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20240315
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 1
DP  - 2010 Jan 6
TI  - Listeriolysin O is necessary and sufficient to induce autophagy during Listeria 
      monocytogenes infection.
PG  - e8610
LID - 10.1371/journal.pone.0008610 [doi]
LID - e8610
AB  - 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 
      microtubule-associated 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.
FAU - Meyer-Morse, Nicole
AU  - Meyer-Morse N
AD  - Department of Molecular and Cellular Biology, University of California, Berkeley, 
      California, United States of America.
FAU - Robbins, Jennifer R
AU  - Robbins JR
FAU - Rae, Chris S
AU  - Rae CS
FAU - Mochegova, Sofia N
AU  - Mochegova SN
FAU - Swanson, Michele S
AU  - Swanson MS
FAU - Zhao, Zijiang
AU  - Zhao Z
FAU - Virgin, Herbert W
AU  - Virgin HW
FAU - Portnoy, Daniel
AU  - Portnoy D
LA  - eng
GR  - P01 AI063302/AI/NIAID NIH HHS/United States
GR  - R01 AI027655/AI/NIAID NIH HHS/United States
GR  - U54 AI057160/AI/NIAID NIH HHS/United States
GR  - AI27655/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100106
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bacterial Toxins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Liposomes)
RN  - R06ZRQ1YX9 (hlyA protein, Listeria monocytogenes)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Bacterial Toxins
MH  - Cells, Cultured
MH  - Heat-Shock Proteins/*physiology
MH  - Hemolysin Proteins/*physiology
MH  - Liposomes
MH  - Listeriosis/*immunology/physiopathology
MH  - Mice
PMC - PMC2797616
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/01/12 06:00
MHDA- 2010/05/21 06:00
PMCR- 2010/01/06
CRDT- 2010/01/12 06:00
PHST- 2009/08/26 00:00 [received]
PHST- 2009/11/03 00:00 [accepted]
PHST- 2010/01/12 06:00 [entrez]
PHST- 2010/01/12 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
PHST- 2010/01/06 00:00 [pmc-release]
AID - 09-PONE-RA-12534R2 [pii]
AID - 10.1371/journal.pone.0008610 [doi]
PST - epublish
SO  - PLoS One. 2010 Jan 6;5(1):e8610. doi: 10.1371/journal.pone.0008610.