The role of the bacterial flagellum in adhesion and virulence

Abstract

The bacterial flagellum is a complex apparatus assembled of more than 20 different proteins. The flagellar basal body traverses the cell wall, whereas the curved hook connects the basal body to the whip-like flagellar filament that protrudes several µm from the bacterial cell. The flagellum has traditionally been regarded only as a motility organelle, but more recently it has become evident that flagella have a number of other biological functions. The major subunit, flagellin or FliC, of the flagellum plays a well-documented role in innate immunity and as a dominant antigen of the adaptive immune response. Importantly, flagella have also been reported to function as adhesins. Whole flagella have been indicated as significant in bacterial adhesion to and invasion into host cells. In various pathogens, e.g., Escherichia coli, Pseudomonas aeruginosa and Clostridium difficile, flagellin and/or the distally located flagellar cap protein have been reported to function as adhesins. Recently, FliC of Shiga-toxigenic E. coli was shown to be involved in cellular invasion via lipid rafts. Here, we examine the latest or most important findings regarding flagellar adhesive and invasive properties, especially focusing on the flagellum as a potential virulence factor.

Figure 1

(A) Schematic presentation of bacterial flagellum structure. The pentameric FliD cap at the distal end of the filament, the hollow filament composed of about 20,000 identical flagellin subunits, the junction zone between filament and hook, and the hook connecting the filament to the basal body, represent extracellular parts (green shades) of the flagellum. The basal body (grey) in the cell wall consists of a centrally located hollow rod that connects different rings embedded in the outer membrane (OM), the peptidoglycan layer, and the cytoplasmic membrane (CM). Stator complexes (dark grey), composed of membrane proteins MotA and MotB, are associated with the CM-bound ring and the cytoplasmic ring below the CM, and provide motility-required energy. The cytoplasmic export machinery (black) that secretes the extracellular subunits is located within the cytoplasmic ring. Note that OM-associated parts of the basal body are absent in the flagella of Gram-positive bacteria. (B) Schematic presentation of flagellin monomer (upper panel) and flagellin polymerization (lower panel). The variable, exposed, globular domains of flagellin are shown in green. The conserved N- and C-terminal regions involved in flagellum polymerization are indicated (blue, light blue, yellow, red) as well as the regions binding to TLR5 (light blue, yellow) and those involved in inflammasome formation (blue, red).

Figure 2

Summary of the bacterial flagellum as an adhesin. Flagellum can mediate bacterial adhesion to eukaryotic cells indirectly via motility (1), or by binding directly to epithelial cells either on apical (2) or basolateral surface (3). Flagellar target receptors include mucus and mucins (4), different glycans on cells or in mucus (gluconate, heparan sulfate proteoglycans, Lewis x glycotype, GM1, asialo-GM1, GD_1a) (5), extracellular matrix (ECM) proteins (6), or bacterial-secreted EtpA, which in turn adheres to host cells (7). Toll-like receptor 5 (TLR5) is expressed mostly at the basolateral cell surface and binds FliC, inducing the host’s immune defense (8). FliC binding also induces TLR5 expression at the apical surface. In addition to various epithelia, flagella may also adhere to amoebae (9) or connect two bacterial species (10).