Architectural dissection of adhesive bacterial cell surface appendages from a "molecular machines" viewpoint

Abstract

The ability of bacteria to interact with and respond to their environment is crucial to their lifestyle and survival. Bacterial cells routinely need to engage with extracellular target molecules, in locations spatially separated from their cell surface. Engagement with distant targets allows bacteria to adhere to abiotic surfaces and host cells, sense harmful or friendly molecules in their vicinity, as well as establish symbiotic interactions with neighboring cells in multicellular communities such as biofilms. Binding to extracellular molecules also facilitates transmission of information back to the originating cell, allowing the cell to respond appropriately to external stimuli, which is critical throughout the bacterial life cycle. This requirement of bacteria to bind to spatially separated targets is fulfilled by a myriad of specialized cell surface molecules, which often have an extended, filamentous arrangement. In this review, we compare and contrast such molecules from diverse bacteria, which fulfil a range of binding functions critical for the cell. Our comparison shows that even though these extended molecules have vastly different sequence, biochemical and functional characteristics, they share common architectural principles that underpin bacterial adhesion in a variety of contexts. In this light, we can consider different bacterial adhesins under one umbrella, specifically from the point of view of a modular molecular machine, with each part fulfilling a distinct architectural role. Such a treatise provides an opportunity to discover fundamental molecular principles governing surface sensing, bacterial adhesion, and biofilm formation.

Keywords: adhesins; bacterial cell surface; biofilms; fimbriae; pili.

Fig 1

Different contexts of bacterial adhesion. Different contexts in which bacterial adhesion can occur are shown schematically (key shown at the bottom). (A) Bacterial adhesion to an abiotic surface using multi-protein pili or single filamentous adhesin molecules, e.g., Pseudomonas aeruginosa T4P, Caulobacter crescentus Tad pilus, Paracoccus denitrificans BapA, and Bordetella pertussis FHA (9–12). (B) Bacterial adhesion to “self,” seen specifically in the context of biofilm formation. Filamentous molecules mediating this type of interaction include the Escherichia coli common pilus, Burkholderia cenocepacia cable pilus, Pseudomonas putida LapF, and Burkholderia pseudomallei BbfA (13–16). (C) Bacterial adhesion to “non-self,” seen in microbiomes or in the context of host cell infection. Examples of the filamentous molecules that interact with non-self-molecules include Corynebacterium diphtheriae SpaA-type pilus, Neisseria meningitidis T4P, Streptococcus pyogenes Sfb1, and Shigella flexneri IcsA (17–20).

Fig 2

Architectural dissection of microbial filamentous surface adhesive appendages. (A) The molecular architecture of a prototypical microbial cell surface adhesive appendage. We propose that all surface appendages must contain three modular parts; first, the presence of an anchoring module, which ensures that the appendage remains bound to the cell. Second, an extension module composed of repeated domains or polymeric proteins enables the appendage to extend away from the cell and out of the dense, sugary network at the cell surface. Third, at the distal end of the appendage, far away from the cell surface, an adhesion module mediates interactions with target molecules. (B) The comparison between a single polypeptide filamentous adhesin and a multi-protein pilus. Despite differences in length, biochemistry, and molecular details, the overall modular molecular architecture of every appendage is the same from a “molecular machines” perspective. We propose that all appendages (fibrillar polypeptides, pili or fimbriae, and even polysaccharides) must contain the three basic modules highlighted in panel A. (C) The overall molecular architecture of examples of a few filamentous appendages described in the text. The colors are the same as panel A to highlight the architectural modularity. Despite differences in molecular details, there is an underlying simplicity in the molecular architecture of filamentous surface adhesive appendages. Panel made using information from references (33, 57, 68, 80, 107, 115).