Pili

  • Overview:
    • Pilus shaft (or fimbrial rod) : contains hundreds (or thousands) of protein subunits (called pilin, 15-25 kDa).
    • Important virulence factors (in UT, GI, genital infections).
    • Targets for vaccination.
    • Have adhesive structure
      • Adhesins 
        • at the tip of pili (hair) or fimbriae (thread or fiber)
        • behave as lectins
        • their ligands = cell receptor (Oligosaccharide residues of glycoprotein or glycolipid receptors)
        • also bind to structural elements of the basement membrane (collagen, fibronectin, etc.)
    • Functions
      • Site for phage attachment
      • DNA transfer
      • Biofilm formation
      • Cell aggregation
      • Cell invasion
      • Motility (twitching)

Pili of G(-) bacteria

  • Structure typically: non-covalent homopolymerization of pilins (form the pilus shaft)
  • Classified into 4 groups (depend on assembly pathways).
    1. Pili with chaperone-usher pathway.
      1. Assembly:
        • The pilin is secreted into the periplasmic space. In there, it binds to specific a chaperone (FimC) which helps protein folding & prevents premature assembly. The complex is then delivered to the outer membrane usher, which serves as a platform for pilus assembly. Adhesive structures: (1.) heteropolymers, flexible fibrillar tip, with a single specific adhesive protein at the end. (2.) homopolymers of non-pilus adhesins 
      2. Members
        1. Type I :
          • found in Enterobacteriaceae & in most E. coli strains
          • is most prevalent type of pilus in uropathogenic Escherichia coli (UPEC) adhesive structure (adhesion causes cystitis). 
          • encoded by the fim gene cluster (fimA-fimH).
          • helical rod (right-handed helical array of 500-3000 copies of FimA) with the size of 6.9 nm thick x 1-2 micrometers long is connected via FimF to a short stubby 3 mm wide linear tip fibrillum containing FimG and the specific adhesin FimH (Fig.1 below)
          • FimH has 2 domains: receptor-binding domain (N-terminal) & pilin domain (C-terminal).
          • FimH binds to mannose-containing receptors. (uroplakins; integral glycoprotein receptors coating luminal surface of bladder epithelium.)
          • FimH binding to bladder cells triggers a signal transduction cascade (leading to actin reorganization, phosphoinositide-3-kinase activation and protein tyrosine phosphorylation).
          • Type I pili are required for initial surface attachment in biofilm formation.
        2. P pili
          • UPEC.
          • Virulent factor (pyelonephritis).
          • Encoded by 11 pap genes (pyelonephritis-associated pili genes).
          • Structure similar to type I pili.
            • Rod (a right-handed helical cylinder) with the dimension of 6.8 nm wide x many micrometers long have PapG adhesin (and three minor pilus proteins PapE, PapF, and PapK) on the tip of fibrillum.
          • Three PapG variants (PapGI, -II, and -III) have different receptor specificity, binding preferentially to globotriaosylceramide or GbO3 (abundant on human uroepithelial cells), globoside or GbO4 (glycolipid iso-receptor of the human kidney, primarily associated with human pyelonephritis & bacteremia), and Forssman antigen or globopentosylceramide, GbO5, (associated with cystitis), respectively
          • flexible tip fibrillum
          • has 2 domains (see Fig. 2)
        3. S pili
          • in E. coli causing sepsis, meningitis, & UTI.
          • SfaS adhesin binds to SA on endothelial cells & to kidney epithelial cell receptors.
          • major SfaA pilins have adhesive properties binding to glycolipids & plasminogen.
        4. Hif pili
          • in Haemophilus influenza
        5. PMF (Proteus mirabilis fimbriae) pili
          • in Proteus mirabilis (cystitis & polynephritis).
          • pmf operon encodes 5 predicted proteins
            • PmfA (major pilin)
            • PmfC (usher)
            • PmfD (chaperone)
            • PmfE (minor pilin)
            • PmfF (adhesin)
        6. Dr/ Afa adhesin family pili
          • with homopolymer adhesin
          • in UPEC
          • in diffusely adhering E. coli (DAEC)
          • encoded by at least 5 afa genes (A-E)
          • AfaE is adhesin
          • most Afa/Dr adhesins recognize DAF (a complement-regulatory membrane protein, on RBC, uroepithelium, and CEACAMs). Fig. 3.
          • AfaE-I, AfaE-III, DraE and DaaE have 2 independently functional binding sites.
          • DraE (not AfaE-III, a homologue) binds to Type IV collagen.
          • may facilitate ascending colonization & chronic infection of UT.
          • some associated with enteric infection.
          • facilitate UPEC invasion of uroepithelial cells.
          • AfaD adhesin has invasin properties.
          • Dr fimbriae can be released into medium (in response to temperature & reduced oxygen).
        7. F1 pili
          • in Yersinia pestis
            • F1 (polymeric capsular antigen)
          • in ETEC (enterotoxigenic E. coli)
            • CFA/I (colonization factor antigen I)
        8. Others (K99, K88, F17, or F6 pili)
          • thinner fibers (2-5 nm thick).
          • mostly associated with animal ETEC.
    2. Type IV pili (more details from here onwards, will be continued on a new page; part 2).
    3. Pili with extracellular nucleation/precipitation pathway (curli pili)
    4. Pili with alternative chaperone-usher pathway (CS1 pilus family)

 

Fig. 1   Type I Pilus (note: FimC = chaperone, FimD = usher)

(Michael Vetsch, et al, 2004)

 

Figure 2  FimH and PapG

(Source: Steve Matthews, Biological Nuclear Magnetic Resonance (NMR))

 

Figure 3 DraE/AfaE Adhesin (green = DAF-binding site, red = CEA-binding site)

(Korotkova et al, 2004)