Taking Control: Campylobacter jejuni Binding to Fibronectin Sets the Stage for Cellular Adherence and Invasion

Abstract

Campylobacter jejuni, a foodborne pathogen, is one of the most common bacterial causes of gastroenteritis in the world. Undercooked poultry, raw (unpasteurized) dairy products, untreated water, and contaminated produce are the most common sources associated with infection. C. jejuni establishes a niche in the gut by adhering to and invading epithelial cells, which results in diarrhea with blood and mucus in the stool. The process of colonization is mediated, in part, by surface-exposed molecules (adhesins) that bind directly to host cell ligands or the extracellular matrix (ECM) surrounding cells. In this review, we introduce the known and putative adhesins of the foodborne pathogen C. jejuni. We then focus our discussion on two C. jejuni Microbial Surface Components Recognizing Adhesive Matrix Molecule(s) (MSCRAMMs), termed CadF and FlpA, which have been demonstrated to contribute to C. jejuni colonization and pathogenesis. In vitro studies have determined that these two surface-exposed proteins bind to the ECM glycoprotein fibronectin (FN). In vivo studies have shown that cadF and flpA mutants exhibit impaired colonization of chickens compared to the wildtype strain. Additional studies have revealed that CadF and FlpA stimulate epithelial cell signaling pathways necessary for cell invasion. Interestingly, CadF and FlpA have distinct FN-binding domains, suggesting that the functions of these proteins are nonredundant. In summary, the binding of FN by C. jejuni CadF and FlpA adhesins has been demonstrated to contribute to adherence, invasion, and cell signaling.

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

“…This is consistent with our result that a combination of adhesin mutant bacteria and the use of chloramphenicol led to the highest restoration of individual cell motility. The requirement of both adhesins and effector proteins for host cell changes is also consistent with the established model of C. jejuni invasion (Konkel et al, 2020;Ó Cróinín & Backert, 2012).…”

“…We have shown that C. jejuni manipulates the size, structure, and composition of focal adhesions. Based on previous research connecting C. jejuni adhesins to focal adhesion components (Konkel, Talukdar, Negretti, & Klappenbach, 2020;Krause-Gruszczynska et al, 2011;Monteville et al, 2003), we hypothesized that the CadF and FlpA adhesins could be responsible for driving the observed changes in the focal adhesion. First, we tested if the CadF and FlpA adhesins were required for signaling changes in the focal adhesion by examining paxillin phosphorylation.…”

Revisiting Campylobacter jejuni Virulence and Fitness Factors: Role in Sensing, Adapting, and Competing

“…C. jejuni adhesins seem to have alternate primary functions, yet some can target the same host receptor such as fibronectin. Once C. jejuni adheres to fibronectin on the basolateral side of human IECs, it is preceded by secondary steps that orchestrate cellular invasion ( Konkel et al., 2020 ). The most highly investigated adhesins in C. jejuni that exist almost in mutually exclusive fashion are Campylobacter adhesion to fibronectin (CadF) and fibronectin-like protein A (FlpA).…”

“…C. jejuni adhesins (CadF and FlpA) are highly conserved among C. jejuni strains. CadF and FlpA proteins are important for C. jejuni adherence to human IECs and colonization of chickens ( Konkel et al., 2020 ). A C. jejuni cadF mutant displays reduced ability to adhere to human IECs and chicken hepatoma cell line, LMH cells.…”

Manipulation of Focal Adhesion Signaling by Pathogenic Microbes

“…The Staphylococcus aureus proteins FnBP-A and FnBP-B were some of the first FnBPs described to indirectly interface with integrin receptors [ 210 ]. Other FnBPs include Streptococcus pyogenes SfbI/Protein F1 [ 208 ] as well as the well-characterized CadF and FlpA made by Campylobacter jejuni [ 204 ]. The gastrointestinal pathogen C. jejuni colonizes polarized intestinal epithelial cells, and this attachment requires fibronectin and CadF.…”