Structure, Function, and Assembly of Type 1 Fimbriae

Abstract

Bacterial infections constitute a major global health problem, acutely accentuated by the rapid spread of antibiotic resistant bacterial strains. The widespread need for bacteria to attach - adhere - to target cells before they can initiate an infection may be used to advantage by targeting the bacterial adhesion tools such as pili and fimbriae for development of novel anti-bacterial vaccines and drugs. Type 1 fimbriae are widely expressed by Escherichia coli. and are used by uropathogenic strains to mediate attachment to specific niches in the urinary tract. These fimbriae belong to a class of fibrillar adhesion organelles assembled through the chaperone/usher pathway, one of the terminal branches of the general secretion pathway in Gram-negative bacteria. Our understanding of the assembly, structure and function of these structures has evolved significantly over the last decade. Here, we summarize current understanding of the function and biogenesis of fibrillar adhesion organelles, and provide some examples of recent progress towards interfering with bacterial adhesion as a means to prevent infection.

The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion

“…Type 1 fimbriae are constructed by a "donor strand exchange" (DSE) process, in which the Ig fold of every subunit is completed by an amino-terminal extension from the following subunit. [21] Figure 5. The type 1 fimbrial rod is assembled from different Fim proteins, which attach to each other by donor strand exchange (DSE).…”

“…The side chains of Tyr48 and Tyr137 are positioned such that they form a gate-like structure that has been named the "tyrosine gate". [21] Thus, mannoside ligands with an aromatic aglycon, such as pNPMan, can establish π-π interactions with the tyrosine gate flanking the entrance of the FimH CRD (Figures 7 and 8), lead- Figure 7. Both graphics show the amino acid residues in an orientation revealed by X-ray diffraction analysis (PDB ID: 1KLF), [78] depicted in ball-and-stick form.…”

“…[20] Type 1 Fimbriae Type 1 fimbriae serve as extremely efficient adhesion tools for bacteria inhabiting diverse environments, including biotic and abiotic surfaces. [21] They are uniformly distributed on Enterobacteriaceae, commonly between 100 and 400 fimbriae per cell. Their length varies between 0.1 to 2 micrometer, their width is approximately 7 nm (Figure 1).…”

Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

“…They vary from medium-sized scaffolds [19][20][21][22][23], to dendrimers [3,24], polymers [25] and nanoparticles [26][27][28][29]. Despite the spacing between fimbriae can vary between strains and depends on growth conditions [30], only the largest of these materials are likely to engage more than one protein at the time, because the FimH binding site can interact with only one mannose residue at the time and each of the fimbriae carries only a single copy of FimH. In most other systems, the multivalency effects observed are not likely to depend on chelation, but rather on increased local concentration of the ligand (statistical rebinding).…”

Schaltung bakterieller Adhäsion auf glycosylierten Oberflächen durch reversible Reorientierung der Kohlenhydratliganden

“…[2,6] Wie bei allen KohlenhydratProtein-Wechselwirkungen ist die Bindung abhängig von der Konstitution und der Konfiguration des Kohlenhydratliganden. Die Kohlenhydraterkennung auf der Zelloberfläche erfolgt allerdings im Kontext der Glycokalyx, einer hochkomplexen Glycokonjugatschicht, die gesunde Zellen mit einer Dicke von 100 nm und mehr umgibt.…”