Pili and Fimbriae of Gram-Negative Bacteria

Research on the function and assembly of extracellular fibres in Gram-negative pathogenic bacteria has provided insights into some of the most basic principles of molecular biology: how a protein folds into domains that serve as assembly modules for building up large supramolecular structures. Studies of the chaperone-usher pathway (CUP) pili have elucidated a reaction called donor strand complementation, in which the chaperone mediates pilus subunit folding, and a reaction called donor strand exchange, in which subunits of a pilus polymerize into a fibre with the aid of the usher, an outer-membrane-gated channel. CUP pili are ubiquitous in Gram-negative bacteria, with many genomes encoding ten or more types, all containing dedicated adhesins that function in adherence, invasion of host tissues, and biofilm formation on medical devices and in various niches and body habitats. Many Gram-negative bacteria also use specific molecular machinery to direct production of amyloid fibres called curli, which can provide structural, adhesive and protective properties to a biofilm. Frequent and long-term prophylactic use of antimicrobial agents has contributed to a looming worldwide crisis of multi-drug resistance that has spawned the need for new ways of thinking about drug development, including the targeting of bacterial molecular machines that catalyse the biogenesis of virulence-associated extracellular fibres.