How bacteria hack the matrix and dodge the bullets of immunity

Abstract

Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa are common Gram-negative pathogens associated with an array of pulmonary diseases. All three species have multiple adhesins in their outer membrane, i.e. surface structures that confer the ability to bind to surrounding cells, proteins or tissues. This mini-review focuses on proteins with high affinity for the components of the extracellular matrix such as collagen, laminin, fibronectin and vitronectin. Adhesins are not structurally related and may be lipoproteins, transmembrane porins or large protruding trimeric auto-transporters. They enable bacteria to avoid being cleared together with mucus by attaching to patches of exposed extracellular matrix, or indirectly adhering to epithelial cells using matrix proteins as bridging molecules. As more adhesins are being unravelled, it is apparent that bacterial adhesion is a highly conserved mechanism, and that most adhesins target the same regions on the proteins of the extracellular matrix. The surface exposed adhesins are prime targets for new vaccines and the interactions between proteins are often possible to inhibit with interfering molecules, e.g heparin. In conclusion, this highly interesting research field of microbiology has unravelled host-pathogen interactions with high therapeutic potential.

FIGURE 1

a and b) Moraxella catarrhalis ubiquitous surface protein (Usp) A2 binds collagen with high affinity. Transmission electron microscopy (TEM) demonstrates that a) gold-labelled recombinant UspA1 does not bind to collagen I fibrils, whereas b) UspA2 does. Reproduced and modified from [17] with permission. c) Bacterial adhesins target laminin globular domains at the base of the asymmetrical cross-shaped laminin. TEM image showing gold-labelled Protein F from nontypeable Haemophilus influenzae bound to laminin. Reproduced and modified from [31] with permission; these images are not included under the Creative Commons CC BY-NC 4.0 licence of the current article. In all panels, gold-labelled recombinant bacterial proteins are marked with white arrows.

FIGURE 2

Moraxella catarrhalis adheres to the extracellular matrix in the respiratory tract. Cartoon that illustrates a disrupted bronchial epithelium and how M. catarrhalis colonises the human lung by using ubiquitous surface protein (Usp) A1 and UspA2 to adhere to laminin, collagen, fibronectin (Fn) and vitronectin (Vn). For simplicity, MID and AfeA were omitted from this cartoon. Reproduced and modified from [17] with permission.

FIGURE 3

Scanning electron micrographs showing that a) Moraxella catarrhalis bacteria (in green pseudocolour) adhere to human tracheal specimens, whereas b) UspA2-deficient mutants do not. Reproduced and modified from [17] with permission.