Systematic Analysis of Bacterial Effector-Postsynaptic Density 95/Disc Large/Zonula Occludens-1 (PDZ) Domain Interactions Demonstrates Shigella OspE Protein Promotes Protein Kinase C Activation via PDLIM Proteins

Abstract

Background: PDZ domains provide specificity in protein-protein interactions in eukaryotic systems. Results: Shigella OspE, which is delivered into human cells during infection, binds PDLIM7 via a PDZ interaction and contributes to activation of PKC. Conclusion: During infection, OspE contributes to activation of PKC through PDZ-mediated binding to PDLIM7. Significance: PDZ interactions likely contribute to pathogenesis of several bacterial pathogens.

Shigella flexneri Disruption of Cellular Tension Promotes Intercellular Spread

“…Bacteria escape this vacuole into the cytosol of the donor cell (Allaoui et al, 1992;Campbell-Valois et al, 2015;Uchiya et al, 1995;Weddle and Agaisse, 2018b), which enables repeated cycles of intercellular spread through the epithelial monolayer. The forces derived from actin-based motility are necessary for protrusion formation (Monack and Theriot, 2001), whereas other pathogen and host factors, including the type 3 secretion translocon pore proteins IpaB and IpaC and the type 3 effectors OspE1/2, IcsB, and VirA, are required for efficient intercellular spread (Allaoui et al, 1995;Campbell-Valois et al, 2014, 2015Heindl et al, 2010;Kuehl et al, 2014;Ogawa et al, 2003;Page et al, 1999;Schuch et al, 1999;Yi et al, 2014;Yoshida et al, 2006). Understanding the molecular mechanisms by which these proteins contribute to spread will define the parameters necessary for bacterial spread.…”

Shigella flexneridisruption of host cell-cell tension promotes intercellular spread

“…Since IpaC interacts with the cell-cell adhesion protein β-catenin (Shaikh et al, 2003), a component of these catenin-cadherin networks, we hypothesized that the role of IpaC in disruption of cell-cell tension may depend on its interaction with β-catenin and that IpaC R362 may be required for this interaction. In an orthogonal yeast-based protein-protein interaction assay that has been successfully used in the study of host-pathogen protein interactions (de Groot et al, 2011; Russo et al, 2016; Schmitz et al, 2009; Yi et al, 2014), we observed that IpaC R362W is defective for interaction with β-catenin. β-catenin (bait) was fused to the reovirus scaffold protein µNS, which forms inclusions bodies, and IpaC derivatives (prey) were tagged with mCherry.…”

“…Bacteria escape this vacuole into the cytosol of the donor cell (Allaoui et al, 1992; Campbell-Valois et al, 2015; Uchiya et al, 1995; Weddle and Agaisse, 2018b), enabling repeated cycles of intercellular spread through the epithelium. Whereas the forces derived from actin-based motility are necessary for protrusion formation (Monack and Theriot, 2001), other pathogen and host factors, including the type 3 secretion translocon pore proteins IpaB and IpaC and the type 3 effectors OspE1/2, IcsB, and VirA, are required for efficient intercellular spread (Allaoui et al, 1995; Campbell-Valois et al, 2015; Campbell-Valois et al, 2014; Heindl et al, 2010; Kuehl et al, 2014; Ogawa et al, 2003; Page et al, 1999; Schuch et al, 1999; Yi et al, 2014; Yoshida et al, 2006). Understanding the molecular mechanisms by which these proteins contribute to spread will define the parameters necessary for bacterial spread.…”

CteG is a Chlamydia trachomatis effector protein that associates with the Golgi complex of infected host cells

“…In the case of EspI/NleA, Golgi targeting is partially mediated by a Postsynaptic Density95/Disc Large/Zonula Occludens-1 (PDZ) domain on its C-terminus 54 . CT105 also possesses a putative PDZ domain 56 , but the relevant residues are not involved in its subcellular localization after ectopic expression in mammalian cells (data not shown).…”