Bacterial Pili and Fimbriae


Bacterial proteinaceous filaments termed pili or fimbriae are nonflagellar, hair‐like structures protruding from the cell surface that are critical for bacterial virulence and fitness. Present in both Gram‐negative and Gram‐positive bacteria, pili are involved in many processes such as conjugation, adherence, twitching motility, biofilm formation and immunomodulation. Considerably diverse and complex, Gram‐negative pili are formed by noncovalent polymerisation of various pilin subunits; many of these pili require chaperones and usher proteins for their assembly. In contrast, fewer pilus systems have been described for the Gram‐positive counterparts; notably well studied are the heterotrimeric or ‐dimeric pili that are covalently assembled by a transpeptidase enzyme called sortase. Furthermore, type IV pili have been identified in several Gram‐positive bacteria, especially in clostridia.

Key Concepts

  • Noncovalent pilus polymerisation is a general mechanism of pilus assembly in Gram‐negative bacteria, including the chaperone/usher assembly pathway and type IV pilus pathway, which generates noncovalent pilus polymers.
  • Sortase‐mediated pilus assembly is a general mechanism of pilus assembly in Gram‐positive bacteria that involves a transpeptidase enzyme named sortase, which cleaves pilin precursors at sorting signals between threonine and glycine residues and utilises the side‐chain amino groups of pilin motif sequences to generate covalent links between pilin subunits.
  • The sorting signal consists of an LPXTG motif followed by a hydrophobic domain and a positively charged tail.
  • The pilin motif is an 11 amino acid sequence of WxxxVxVYPKN located near the N‐terminus of major pilin subunits, in which the electron‐donating lysine residue forms an isopeptide bond with the threonine residue generated from the cleavage of the LPXTG motif of adjacent pilin subunits.
  • Tissue tropism is referred to as the ability of a pathogen to adhere specifically to some particular epithelial cells.
  • Phase variation involves switching of surface antigens such as pili that allows a pathogen to evade the host immune system.
  • Immunomodulation is a process of changing the host's immune system by certain molecules known as immunomodulators including pili that can activate or suppress immune cells.
  • Dental plaque is one of the most complex bacterial biofilms that is formed by sequential colonisation of initial colonisers such as Actinomyces spp. and oral streptococci and late colonisers; this process involves Actinomyces fimbriae.
  • Twitching motility mediated by pili allows translocation between mucosal surfaces, colonisation of host tissues and establishment of biofilms by a pathogen.

Keywords: pili; fimbriae; adhesion; polymerisation; sortase

Figure 1. Assembly mechanisms of P pili assembled by the chaperone/usher pathway and Type V pili. P subunits (PapA, E, F, G, H, K) are translocated across the cytoplasmic membrane by the Sec machinery and they interact sequentially with the periplasmic disulfide isomerase DsbA and the chaperone PapD. DsbA mediates disulfide bond formation in the subunits and PapD, and it is required for the correct folding of PapD. PapD is needed for the release of subunits from the cytoplasmic membrane and for the proper folding of the subunits via donor strain complementation. In the absence of PapD, subunits enter into nonproductive aggregations that are sensed by the Cpx and σE signal transduction pathways (not shown). Chaperone–subunit complexes are targeted to PapC in the outer membrane, where subunit–subunit interactions lead to the formation and translocation of a linear pilus fibre across the outer membrane through the usher channel. Once on the cell surface, the pilus rod can twist into its final helical conformation, which may facilitate secretion of the pilus. Type V pilus assembly in P. gingivalis begins with secretion of prepilins into the periplasm followed by secretion through the outer membrane where an arginine or lysine‐specific proteinase cleaves one β sheet from the N‐terminal domain. Assembly of the pilus occurs through interactions between the channel created from proteinase cleavage and a flexible C‐terminal extension of another pilin. Type V pili are anchored directly to the outer membrane through lipidation of the N‐terminus of the anchor pilin. Adapted from Li and Thanassi , Thanassi and Hultgren .
Figure 2. Assembly of type IV pili in Gram‐negative bacteria. For the assembly and retraction of type IV pili, prepilin leader sequences are cleaved and N‐methylated by prepilin peptidase PilD. PilA is assembled on a base of PilE, V, W, X and FimU by the cytoplasmic membrane protein PilC and the NTP‐binding protein PilB. The pilus grows through the outer membrane pore composed of multimeric PilQ, which is stabilised by the lipoprotein PilP. Pili are retracted by ATPase PilT that is aided by PilU. Mattick . Reproduced with permission of Annual Review of Microbiology.
Figure 3. A biphasic model of sortase‐mediated pilus assembly in Gram‐positive bacteria with the prototype SpaA pili of Corynebacterium diphtheriae. Spa pilin precursors (SpaA, SpaB and SpaC) are translocated across the membrane by the Sec machinery with the removal of their leader peptide sequences. Folding of pilins is mediated by MdbA before the cleaved pilins are anchored to the cytoplasmic membrane by the sorting signal, which is compromised of an LPXTG sequence motif, followed by a hydrophobic domain and tail of positively charged residues (+). Sortases cleave the LPXTG motif between threonine and glycine, forming acyl–enzyme intermediates with the pilin substrates. Pilus polymerisation occurs by lysine‐mediated transpeptidation reactions catalysed by pilus‐specific sortase. This polymerisation is terminated when SpaB is attached to the pilus base by the housekeeping sortase. The housekeeping sortase catalyses cell wall anchoring of pilus polymers. Adapted from Mandlik et al. .


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Further Reading

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Ramirez, Nicholas A, and Ton‐That, Hung(Mar 2020) Bacterial Pili and Fimbriae. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000304.pub3]