Structure and Function of Hib Pili fromHaemophilus influenzaeType b

Abstract

Pathogenic bacteria are specifically adapted to bind to their customary host. Disease is then caused by subsequent colonization and/or invasion of the local environmental niche. Initial binding of Haemophilus influenzae type b to the human nasopharynx is facilitated by Hib pili, filaments expressed on the bacterial surface. With three-dimensional reconstruction of electron micrograph images, we show that Hib pili comprise a helix 70 Å in diameter with threefold symmetry. The Hib pilus filament has 3.0 subunits per turn, with each set of three subunits translated 26.9 Å along and rotated 53 degrees about the helical axis. Amino acid sequence analysis of pilins from Hib pili and from P-pili expressed on uropathogenic Escherichia coli were used to predict the physical location of the highly variable and immunogenic region of the HifA pilin in the Hib pilus structure. Structural differences between Hib pili and P-pili suggest a difference in the strategies by which bacteria remain bound to their host cells: P-pili were shown to be capable of unwinding to five times their original length (E. Bullitt and L. Makowski, Nature 373:164-167, 1995), while damage to Hib pili occurs by slight shearing of subunits with respect to those further along the helical axis. This capacity to resist unwinding may be important for continued adherence of H. influenzae type b to the nasopharynx, where the three-stranded Hib pilus filaments provide a robust tether to withstand coughs and sneezes.

Evolution of the Chaperone/Usher Assembly Pathway: Fimbrial Classification Goes Greek

“…The hif operon of H. influenzae (341,349) encodes fimbriae that agglutinate erythrocytes carrying the blood group AnWj antigen (64) and promotes colonization of the upper respiratory tract (108,109,184,350). The 7-nm-wide fimbrial filaments are composed of a helical shaft containing three copies of the HifA major subunit per turn (228). The filaments carry a short tip fibrillum composed of the minor subunit HifD (312), which contains the minor subunit HifE located at its tip (221).…”

Nanoscale Structural and Mechanical Properties of Nontypeable Haemophilus influenzae Biofilms

“…Fimbriae of different strains of H. influenzae bacteria have been visualized in great detail using electron microscopy (EM), particularly transmission EM (TEM) (10,20,33,41,52,69). In addition, their LOS composition has been extensively investigated by electrophoretic and mass spectrometric methods (11,15,38,39,44).…”

Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli

“…The structural differences between fimbriae appear correlated with the host niche environment rather than class designation, as P-pili (class 1) and CFA/I (class 5) fimbriae appear more structurally similar to each other than to Hib pili (class 1). Unwinding is observed in both P-pili and CFA/I fimbriae, whereas this fibrillar conformation is not seen in Hib pili that survive in an environment of even higher shear forces (28).…”