The attachment of bacteria to host tissues marks a critical early step in the development of infectious diseases. Pili are fibrous organelles expressed on the surface of Gram-negative bacteria that mediate attachment to host tissues. Institute researchers have used the P pilus from uropathogenic E.coli as a model system to understand pilus structure, pilus biogenesis, and pilus-mediated attachment. The P pilus has been shown to be critical to the development of pyelonephritis, and infection of the kidney. The assembly of P pili proceeds by the highly conserved chaperone-usher pathway, which participates in the biogenesis of at least thirty diverse surface organelles on Gram-negative bacterial pathogens. Chaperone-subunit complexes are specifically targeted to the outer membrane usher, PapC, where the subunits polymerize to form a pilus. Solving the structure of chaperone-subunit complexes and ushers has led to the elucidation of the mechanism of usher-mediated pilus biogenesis. This structural knowledge is being exploited for the design of novel compounds capable of inhibiting pilus biogenesis.

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