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Cyclophilin A is crucial for efficient Listeria Cell‐to‐Cell Spreading
Author(s) -
Dhanda Arandeep Singh,
Lulic Katarina T,
Vogl A Wayne,
McGee Margaret M,
Chiu Robert H,
Guttman Julian A
Publication year - 2019
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.2019.33.1_supplement.610.5
Subject(s) - cypa , cyclophilin a , listeria monocytogenes , listeria , biology , microbiology and biotechnology , actin , cell , bacteria , genetics
Listeria monocytogenes ( Listeria ) bacteria kill 25% of people they infect. To cause disease, these microbes enter their host's cells and commandeer various components of those cells. Importantly, the bacteria generate motile actin‐rich structures attached to their own surface in order to protrude from the host cell's plasma membrane as they attempt to spread into neighboring cells for further infections. These actively spreading bacteria reside within the tips of protrusive actin‐rich structures called listeriopods. To better understand infections caused by Listeria , current research is targeted towards unravelling the precise molecular components involved in the formation of listeriopods. In a screen of proteins found at actin‐rich structures formed by pathogenic Escherichia coli ( E. coli ), we identified the eukaryotic peptidyl prolyl cis‐trans isomerase (PPIase), cyclophilin A (CypA). Here we tested the hypothesis that CypA is a crucial protein needed to propagate infections by Listeria . Using CypA antibodies we demonstrate that this protein is concentrated specifically at listeriopods. To test the functional importance of CypA at these structures we infected CypA null murine fibroblasts with Listeria and saw that listeriopods were structurally collapsed and twisted. Ultrastructural examination revealed wide‐scale alterations to the organization of actin filaments within the core of the collapsed listeriopods. Importantly, when CypA is re‐expressed in these null cells, listeriopods appear morphologically normal. We used a Listeria cell‐to‐cell spreading assay to examine the ability of listeriopods to protrude into neighboring uninfected cells and found a ~2.5‐fold decrease in the proportion of listeriopods moving cell‐to‐cell when they were generated in CypA knock‐out cells. In conclusion, we have shown that CypA is a key protein needed for bacterial cell‐to‐cell dissemination. Support or Funding InformationGrant Funding Source: NSERC (grant no. 355316 to J.A.G), SFU departmental funds and SFU Multi‐Year Funding (A.S.D) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .