Open AccessAutophagy Facilitates Salmonella Replication in HeLa Cells
Author(s) -
Hong Yu,
Matthew A. Croxen,
Amanda M. Marchiando,
Rosana B. R. Ferreira,
Ken Cadwell,
Leonard J. Foster,
B. Brett Finlay
Publication year - 2014
Publication title -
mbio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.562
H-Index - 121
eISSN - 2161-2129
pISSN - 2150-7511
DOI - 10.1128/mbio.00865-14
Subject(s) - autophagy , salmonella , cytosol , microbiology and biotechnology , hela , biology , intracellular , autophagosome , intracellular parasite , phagosome , lysosome , cell , biochemistry , bacteria , genetics , apoptosis , enzyme
Autophagy is a process whereby a double-membrane structure (autophagosome) engulfs unnecessary cytosolic proteins, organelles, and invading pathogens and delivers them to the lysosome for degradation. We examined the fate of cytosolicSalmonella targeted by autophagy and found that autophagy-targetedSalmonella present in the cytosol of HeLa cells correlates with intracellular bacterial replication. Real-time analyses revealed that a subset of cytosolicSalmonella extensively associates with autophagy components p62 and/or LC3 and replicates quickly, whereas intravacuolarSalmonella shows no or very limited association with p62 or LC3 and replicates much more slowly. Replication of cytosolicSalmonella in HeLa cells is significantly decreased when autophagy components are depleted. Eventually, hyperreplication of cytosolicSalmonella potentiates cell detachment, facilitating the dissemination ofSalmonella to neighboring cells. We propose thatSalmonella benefits from autophagy for its cytosolic replication in HeLa cells.IMPORTANCE As a host defense system, autophagy is known to target a population ofSalmonella for degradation and hence restrictingSalmonella replication. In contrast to this concept, a recent report showed that knockdown of Rab1, a GTPase required for autophagy ofSalmonella , decreasesSalmonella replication in HeLa cells. Here, we have reexamined the fate ofSalmonella targeted by autophagy by various cell biology-based assays. We found that the association of autophagy components with cytosolicSalmonella increases shortly after initiation of intracellular bacterial replication. Furthermore, through a live-cell imaging method, a subset of cytosolicSalmonella was found to be extensively associated with autophagy components p62 and/or LC3, and they replicated quickly. Most importantly, depletion of autophagy components significantly reduced the replication of cytosolicSalmonella in HeLa cells. Hence, in contrast to previous reports, we propose that autophagy facilitatesSalmonella replication in the cytosol of HeLa cells.