Therapeutic approaches targeting the assembly and function of chaperone-usher pili

The chaperone-usher (CU) pathway is dedicated to the biogenesis of surface structures termed pili or fimbriae that play indispensable roles in the pathogenesis of a wide range of bacteria (^1-4). Pili are hair-like fibers composed of multiple different subunit proteins. They are typically involved in adhesion, allowing bacteria to establish a foothold within the host. Following attachment, pili modulate host cell signaling pathways, promote or inhibit host cell invasion, and mediate bacterium-bacterium interactions leading to formation of community structures such as biofilms (^{5, 6}). Gram-negative bacteria express multiple CU pili that contribute to their ability to colonize diverse environmental niches (^{1, 7-10}). Pili thus function at the host-pathogen interface to both initiate and sustain infection and represent attractive therapeutic targets.