Structure of the Pseudomonas aeruginosa fibrillar adhesin CdrA reveals a clawlike domain and modular repeats

Fibrillar adhesins are predicted to be widely abundant across different bacterial species and are key to important bacterial functions (e.g., surface adherence, biofilm formation). However, there is a general paucity of structural data describing fibrillar adhesins, especially for full-length proteins. In this study, we used an integrative approach to experimentally refine the structure of CdrA, a fibrillar adhesin produced by the opportunistic pathogen Pseudomonas aeruginosa , that promotes the formation of bacterial aggregates called biofilms. Specifically, we incorporated both cryo-electron microscopy and solid-state NMR to generate restraints that permitted computational refinement of the full-length CdrA structure. We observed that CdrA has two structurally distinct domains, an extension domain that encompasses nearly identical tandem repeat modules and is capped by a putative adhesive domain with two subdomains that together resemble a claw. This study provides a foundation for understanding bacterial surface attachment and biofilm formation, which could aid in the development of future anti-biofilm therapeutics.