Archaic chaperone-usher pili self-secrete into superelastic zigzag springs.

Pakharukova N, Malmi H, Tuittila M, Dahlberg T, Ghosal D, Chang YW, Myint SL, Paavilainen S, Knight SD, Lamminmäki U, Uhlin BE, Andersson M, Jensen G, Zavialov AV

Nature 609 (7926) 335-340 [2022-09-00; online 2022-07-19]

Adhesive pili assembled through the chaperone-usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria1-3. Archaic chaperone-usher pathway pili, the most diverse and widespread chaperone-usher pathway adhesins, are promising vaccine and drug targets owing to their prevalence in the most troublesome multidrug-resistant pathogens1,4,5. However, their architecture and assembly-secretion process remain unknown. Here, we present the cryo-electron microscopy structure of the prototypical archaic Csu pilus that mediates biofilm formation of Acinetobacter baumannii-a notorious multidrug-resistant nosocomial pathogen. In contrast to the thick helical tubes of the classical type 1 and P pili, archaic pili assemble into an ultrathin zigzag architecture secured by an elegant clinch mechanism. The molecular clinch provides the pilus with high mechanical stability as well as superelasticity, a property observed for the first time, to our knowledge, in biomolecules, while enabling a more economical and faster pilus production. Furthermore, we demonstrate that clinch formation at the cell surface drives pilus secretion through the outer membrane. These findings suggest that clinch-formation inhibitors might represent a new strategy to fight multidrug-resistant bacterial infections.

Cryo-EM [Service]

PubMed 35853476

DOI 10.1038/s41586-022-05095-0

Crossref 10.1038/s41586-022-05095-0

pmc: PMC9452303
pii: 10.1038/s41586-022-05095-0

Publications 9.5.0