Interaction with the host: the role of fibronectin and extracellular matrix proteins in the adhesion of Gram-negative bacteria

Abstract

The capacity of pathogenic microorganisms to adhere to host cells and avoid clearance by the host immune system is the initial and most decisive step leading to infections. Bacteria have developed different strategies to attach to diverse host surface structures. One important strategy is the adhesion to extracellular matrix (ECM) proteins (e.g., collagen, fibronectin, laminin) that are highly abundant in connective tissue and basement membranes. Gram-negative bacteria express variable outer membrane proteins (adhesins) to attach to the host and to initiate the process of infection. Understanding the underlying molecular mechanisms of bacterial adhesion is a prerequisite for targeting this interaction by "anti-ligands" to prevent colonization or infection of the host. Future development of such "anti-ligands" (specifically interfering with bacteria-host matrix interactions) might result in the development of a new class of anti-infective drugs for the therapy of infections caused by multidrug-resistant Gram-negative bacteria. This review summarizes our current knowledge about the manifold interactions of adhesins expressed by Gram-negative bacteria with ECM proteins and the use of this information for the generation of novel therapeutic antivirulence strategies.

Keywords: Adhesins; Collagen; Extracellular matrix proteins; Fibronectin; Gram-negative bacteria; Laminin.

Fig. 1

Schematic drawing of the fibronectin molecule (monomer) with selected bacterial protein-binding sites and selected host protein–protein interaction sites. Fibronectin (Fn) is a heterodimer composed of two splice variants connected by a C-terminal disulfide bond. The molecule contains nine Fn type I repeats, two Fn type II repeats, and between 15 and 18 Fn type III repeats. In cellular Fn, EIIIA (A) and EIIIB (B) domains are present as a result of alternative splicing Adapted from [202]

Fig. 2

Schematic drawing of the laminin molecule (heterotrimer) with selected bacterial protein-binding sites and selected host protein–protein interaction sites. Laminin (Ln) consists of α- (400 kDa), β- (200 kDa), and γ- (200 kDa) chains interconnected with disulfide bonds. Ln domains (N-terminus) are involved in the polymerization of the molecule. The epidermal growth factor-like (LE) domains interconnect the globular domains. The coiled-coil region is present in all chains and their interactions maintain the structure. The C-terminus contains five globular domains (G1–G5) important for cellular scaffold functions