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Cyclophilin A is Crucial for Listeria and Salmonella Invasion and Cell‐to‐Cell Spreading
Author(s) -
Dhanda Arandeep,
Warren Kiera,
Guttman Julian
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.226.4
Subject(s) - cypa , microbiology and biotechnology , membrane ruffling , cyclophilin a , actin , biology , listeria monocytogenes , cytoplasm , listeria , actin cytoskeleton , motility , cell , cytoskeleton , bacteria , biochemistry , genetics
The actin cytoskeleton is a common target for a variety of pathogens. Listeria monocytogenes ( Listeria ) bacteria control the actin polymerization machinery within eukaryotic cells for their entry, intracellular motility and subsequent spreading from one cell to another. These microbes use actin‐rich structures called comet tails to generate protrusions at the plasma membrane (referred to as listeriopods) for cell‐to‐cell spreading. Unfortunately, the precise molecular mechanisms governing this process remain elusive. Another actin‐hijacking bacterial pathogen is Salmonella typhimurium ( Salmonella ). These bacteria exploit actin‐based membrane ruffling in order to enter cells. Although actin regulators have been linked to this process, a thorough understanding of the molecular constituents and their functions at these structures has not yet been investigated. We have previously shown that the peptidyl prolyl cis‐trans isomerase (PPIase), cyclophilin A (CypA), a cytosolic protein involved in protein folding, is recruited to actin‐rich structures generated by Listeria . Here we expanded on our previous discovery and tested the hypothesis that CypA is important for the pathogenesis of Listeria . Infections of murine fibroblasts depleted of CypA revealed that listeriopods were structurally collapsed, suggesting a unique role of cellular PPIases during cell‐to‐cell spreading of Listeria . Importantly, when CypA was reexpressed in these cells, listeriopods appeared normal. Curiously, cytoplasmic comet tails remained morphologically unchanged when CypA was absent. We also found that CypA is recruited to actin‐rich membrane ruffles generated by Salmonella during its entry into cells. Surprisingly, invasion assays of murine fibroblasts showed that invasion by Listeria and Salmonella increases significantly in cells knocked‐out for CypA. These results suggest a novel membrane‐associated mechanism whereby CypA regulates the efficiency of invasion and cell‐to‐cell transmission of bacteria. Support or Funding InformationGrant Funding Source: NSERC and departmental funds