Campylobacter jejuni trigger signaling through host cell focal adhesions to inhibit cell motility and impede wound repair

Abstract

Campylobacter jejuni is a major foodborne pathogen that exploits the focal adhesions of intestinal cells to promote invasion and cause severe gastritis. Focal adhesions are multiprotein complexes involved in bidirectional signaling between the actin cytoskeleton and the extracellular matrix. We investigated the dynamics of focal adhesion structure and function in C. jejuni infected cells. We found that C. jejuni infection of epithelial cells results in an increased focal adhesion size, enhanced signaling, and altered topology, as demonstrated by confocal microscopy, immunoblots, and super-resolution iPALM. Infection by C. jejuni also resulted in an increase in cell adhesion strength, reduced host cell motility, and reduction of collective host cell migration, a fundamental step in intestinal villi healing. Mechanistic studies demonstrated that the C. jejuni fibronectin-binding proteins CadF and FlpA are involved in the changes in focal adhesion dynamics and alterations in cell behavior. These findings are important because they provide a putative mechanistic basis for the restricted intestinal repair observed in C. jejuni-infected animals and raise the possibility that bacterial adhesins that target extracellular matrix components can alter cell behavior by manipulating focal adhesions.