The Chaperone-Usher Pathway of Pilus Fiber Biogenesis

Abstract

Many species of gram-negative bacteria employ a conserved protein secretion system termed the chaperone-usher pathway to assemble a diverse array of multisubunit protein fibers on their surfaces. Fibers assembled by the chaperone-usher pathway play critical roles in bacterially mediated disease: they mediate bacterial attachment to host tissues, often an essential early step in pathogenesis; they facilitate the evasion of host defenses; and they promote biofilm formation, a contributing factor both to the establishment of infection and to bacterial resistance to antibiotic treatment. Fibers assembled by the chaperone-usher pathway are typically encoded in individual gene clusters. The well-studied surface organelles, the capsular F1 antigen of Yersinia pestis and the hemagglutinating pilus of the human respiratory pathogen Haemophilus influenzae, highlight the structural diversity of fibers assembled by the chaperone-usher pathway. The periplasmic chaperones of the chaperone-usher pathway share conserved structural features first revealed in the crystal structure of PapD. Each chaperone consists of two domains that are oriented at an approximate right angle to each other to produce an L-shaped molecule. Donor strand exchange occurs very rapidly in vivo but only relatively slowly and inefficiently in vitro in the absence of the usher. This suggests that while the chaperone primes the subunit for donor strand exchange, additional interactions with the usher may facilitate subunit uncapping during fiber formation. The relative specificity of donor strand exchange determines, at least in part, the function of individual subunits and their order of incorporation into the fiber.