# Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure
## 6 Filament-Host Interaction
### Filaments Are Directly Involved in Surface Adhesion  
Flagella-mediated adhesion to plasma membranes is a crucial step that allows bacteria to penetrate and colonize the mucus layers of their hosts and invade the tissues [159]. The adherence of _C. jejuni_ to intestinal cells is dependent on flagella in combination with LPS, while in _Aeromonas caviae_ cells without polar flagellum were almost completely  
Figure 6: Flagellar filament, flagellin and FliD are implicated in various processes.  
nonadherent [161, 162]. Flagellin and/or flagellar cap proteins have been identified as adhesins in other pathogens such as _E. coli_, _C. difficile_, and _P. aeruginosa_.  
Mucin is an important target for _P. aeruginosa_ adhesion as the lung epithelium contains a thick mucus layer. In the _P. aeruginosa_ PAK strain, FliD appears to mediate the adhesion to mucins and this is not due to its effect on filament formation, since the mutant in which FliC was abrogated still binds mucins [163, 164]. Conversely, in the PAO1 strain FliC participates in mucin adhesion [165]. Moreover, the same study indicated that FliC and FliD of PAO1 bind Lewis\({}^{X}\) glycotopes which are typically found on the airway mucins, while FliD from the PAK strain does not [165]. In the case of binding to Muc1, however, it appears that deleting _fliC_ in the PAK strain abolishes adhesion, while deletion of _fliD_ has no effect [166]. This finding is surprising considering that FliD is necessary for filament formation. In addition, PAK-_fliC_ is impaired in adhesion to human airway epithelial cells and exhibits reduced virulence in a mouse model of pneumonia.  
Similarly, _E. coli_ flagellin is also important for adhesion, as in enteropathogenic _E. coli_ (EPEC), or in enterotoxicin _E. coli_ (ETEC), where it works in concert with an exoprotein adhesin EtpA by capturing and presenting it to the eukaryotic receptors [167, 168]. Among _E. coli_ strains, the differences in flagellin determine their ability to adhere to specific surfaces. For example, the FliC of enterohaemorrhagic _E. coli_ (EHEC), but not of EPEC, provides specific binding to the bovine terminal rectal epithelium and agglutinates rabbit red blood cells, while EPEC FliC binds to collagen, and to a lesser degree laminin and fibronectin [169, 170]. Not only pathogenic, but also probiotic, _E. coli_ possess adhesive flagella that are important for gut colonization. Such is the case for the _E. coli_ Nissle 1917 strain in which deletion of _fliC_ abolishes the adhesion to the intestinal epithelium, an interaction that is mediated through the mucus component gluconate [171]. On the other hand, when it comes to the direct role of flagellin and FliD in adhesion in _C. difficile_ and _H. pylori_, reports are somewhat contradictory in the literature, with some studies showing their direct involvement in different cell types [172, 173], while others suggest that their importance is limited to providing motility while other adhesins mediate binding to colonize the gastric epithelial cells [159, 174].  
Membrane lipid composition and physical properties of the lipid bilayer, such as membrane fluidity and head-group lipid packing, have been shown to be key parameters that enable flagellar adhesion. Saturated fatty acids provide optimal binding of flagella, while polyunsaturated fatty acids prevent bacterial adhesion on membrane bilayers and play a key role for optimal host colonization [175]. It has been observed that flagella preferentially bind to cholesterol and sphingolipid-enriched lipid microdomains and that flagellin is required for adhesion to lipid rafts in host cells. Indeed, _S. typhimurium_ flagella have been shown to interact with a cholesterol-coated surface; adhesion was significantly reduced in _\(\Delta\)fliC_ mutant [176].