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

: Pakharukova Natalia, Malmi Henri, Tuittila Minna, Dahlberg Tobias, Ghosal Debnath, Chang Yi-Wei, Myint Si Lhyam, Paavilainen Sari, Knight Stefan David, Lamminmäki Urpo, Uhlin Bernt Eric, Andersson Magnus, Jensen Grant, Zavialov Anton V.

Publisher: Nature Portfolio

: 2022

: Nature

: NATURE

: 609

: 7926

: 335

: 340

: 23

: 0028-0836

: 1476-4687

DOI: https://doi.org/10.1038/s41586-022-05095-0

: https://www.nature.com/articles/s41586-022-05095-0

: https://research.utu.fi/converis/portal/detail/Publication/176483189

Adhesive pili assembled through the chaperone-usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria(1-3). 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 pathogens(1,4,5). 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.

s41586-022-05095-0.pdf