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

Natalia Pakharukova, Henri Malmi, Minna Tuittila, Tobias Dahlberg, Debnath Ghosal, Yi-Wei Chang, Si Lhyam Myint, Sari Paavilainen, Stefan David Knight, Urpo Lamminmäki, Bernt Eric Uhlin, Magnus Andersson, Grant Jensen and Anton V. Zavialov ()
Additional contact information
Natalia Pakharukova: University of Turku
Henri Malmi: University of Turku
Minna Tuittila: University of Turku
Tobias Dahlberg: Umeå University
Debnath Ghosal: California Institute of Technology
Yi-Wei Chang: California Institute of Technology
Si Lhyam Myint: Umeå University
Sari Paavilainen: University of Turku
Stefan David Knight: Uppsala University
Urpo Lamminmäki: University of Turku
Bernt Eric Uhlin: Umeå University
Magnus Andersson: Umeå University
Grant Jensen: California Institute of Technology
Anton V. Zavialov: University of Turku

Nature, 2022, vol. 609, issue 7926, 335-340

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41586-022-05095-0

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