Listeria monocytogenesInlP interacts with afadin and facilitates basement membrane crossing

Abstract

26During pregnancy, the placenta protects the fetus against the maternal immune response, as well 27 as bacterial and viral pathogens. Bacterial pathogens that have evolved specific mechanisms of 28 breaching this barrier, such as Listeria monocytogenes, present a unique opportunity for learning 29 how the placenta carries out its protective function. We previously identified the L. 30 monocytogenes protein Internalin P (InlP) as a secreted virulence factor critical for placental 31 infection (1). Here, we show that InlP, but not the highly similar L. monocytogenes internalin 32Lmo2027, binds to human afadin (encoded by AF-6), a protein associated with cell-cell junctions. were deficient in their ability to form actin-rich protrusions from the basal face of polarized 39 epithelial monolayers, a necessary step in the crossing of such monolayers (transcytosis). A 40 similar phenotype was observed for bacteria expressing an internal in-frame deletion in inlP (inlP 41 DLRR5) that specifically disrupts its interaction with afadin.

Listeria monocytogenescell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

“…Whereas at least a few of the pioneer events that we directly observed in MDCK cells appear to involve long apical protrusions, in the intestinal epithelium, which is characterized by a dense and highly-organized apical brush border (Crawley et al, 2014), it is probably more likely that pioneers would spread either laterally between cells in the epithelium or basally at the junction between the enterocytes and the subjacent basement membrane. Indeed, L. monocytogenes' ability to cross the basal membrane of an epithelium via an actin-dependent process has been well-characterized (Faralla et al, 2018). The key feature of these protrusions, however, is that they enable an L. monocytogenes bacterium to bypass several host cells on its way to the more distant recipient cell.…”