Cyclophilin A, a Novel Component of Listeria monocytogenes Comet Tails

The intracellular bacterium Listeria monocytogenes hijacks the actin polymerization machinery within human cells for its entry, intracellular movement and subsequent spreading from cell‐to‐cell. Intracellular motility of Listeria involves Arp2/3‐mediated actin polymerization at one pole of the bacteria, resulting in the generation of structures known as comet tails. During cell‐to‐cell spreading, comet tails protrude from the host cell membrane from structures referred to as listeriopods. Although the minimal protein constituents required for these actin‐based structures were identified years ago, a complete understanding of the molecular constituents and their specific functions at these sites remains to be investigated. Cyclophilin A (CypA) is a cytosolic protein involved in protein folding and potentially actin nucleation. Thus, because Listeria depends on actin‐based structures for crucial events in its disease process, we tested the hypothesis that CypA is recruited to Listeria comet tails and sites of cell‐to‐cell bacterial spreading. Through the use of fluorescently‐tagged CypA DNA constructs and time‐lapse imaging, we demonstrate that CypA is present at 1) the surface of Listeria prior to comet tail formation, 2) comet tails themselves and 3) listeriopods. Our data reveals a new component in the actin‐based motility of Listeria and suggests that CypA may play a crucial role in the cell‐to‐cell spreading of Listeria. Grant Funding Source : NSERC and departmental funds