Structural basis of biofilm formation mediated by the Pseudomonas aeruginosa fibrillar adhesin CdrA

Authors

Smith, O. E. R., Clemente, C. M., Andreeva, A., Wang, Z., Weimann, A., Dinan, A. M., Houghton-Flory, C., Tarafder, A. K., Boehning, J., O'Toole, G. A., Floto, R. A., Mobarec, J.-C., Bateman, A., Bharat, T.

Abstract

Many bacteria, including the important human pathogen Pseudomonas aeruginosa, are naturally found in antibiotic-tolerant, multicellular biofilms. Cell-cell interactions within P. aeruginosa biofilms are mediated by a large fibrillar adhesin called CdrA in an extracellular polysaccharide-dependent manner. Here, we report an electron cryomicroscopy structure of the 60 kDa CdrA adhesive N-terminus, which combined with electron cryotomography of focused-ion beam milled specimens, allows us to derive a complete in situ model of the native adhesin. Our structure reveals a small adhesive domain (called ADEPT) at the distal tip of CdrA that is nearly perfectly conserved across the P. aeruginosa pangenome, with structural similarity to previously reported sugar-binding domains in multiple bacterial species. Inhibitory nanobodies targeting CdrA that reduce biofilm formation bind to epitopes in, or close to, the ADEPT on bacterial cells. Furthermore, structure-guided mutagenesis of residues within the ADEPT abolishes bacterial aggregation, and genomic deletion of the whole ADEPT leads to strong attenuation of biofilm formation. Our data forms a rational basis for future targeted inhibition of pathogenic P. aeruginosa biofilms and elucidates the mechanism of biofilm formation mediated by fibrillar adhesins that are widespread in bacteria.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 15 Jul 2026.

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