The Pseudomonas aeruginosa Biofilm Matrix Protein CdrA Has Similarities to Other Fibrillar Adhesin Proteins

Abstract

The ability of bacteria to adhere to each other and both biotic and abiotic surfaces is key to biofilm formation, and one way that bacteria adhere is using fibrillar adhesins. Fibrillar adhesins share several key characteristics, including (i) they are extracellular, surface-associated proteins, (ii) they contain an adhesive domain as well as a repetitive stalk domain, and (iii) they are either a monomer or homotrimer (i.e., identical, coiled-coil) of a high molecular weight protein. Pseudomonas aeruginosa uses the fibrillar adhesin called CdrA to promote bacterial aggregation and biofilm formation. Here, the current literature on CdrA is reviewed, including its transcriptional and posttranslational regulation by the second messenger c-di-GMP as well as what is known about its structure and ability to interact with other molecules. I highlight its similarities to other fibrillar adhesins and discuss open questions that remain to be answered toward a better understanding of CdrA.

Keywords: CdrA; Pseudomonas aeruginosa; biofilms; fibrillar adhesin.

FIG 1

Model demonstrating c-di-GMP control of CdrA at both the transcriptional and posttranslational levels. Binding of c-di-GMP to FleQ converts FleQ from a repressor to an activator of cdrAB transcription. CdrA requires the pore, CdrB, to be exported from the periplasm to the extracellular space. The periplasmic protease LapG cleaves CdrA at its C terminus under conditions of low c-di-GMP, resulting in release of CdrA from the bacterial cell surface. Extracellular CdrA can undergo further proteolytic processing by the protease LasB. (Adapted from references and .)

FIG 2

Structural models of CdrA. (A) The structural model of CdrA that was first published is approximately 30 nm from residue 438 to 2105, and it is rich in parallel beta-sheets (10). (B) The more recent model, which was obtained using AlphaFold, is approximately 70 nm from residue 438 to 2105. For both models, the region between residues 438 and 2105 is shown; the putative binding domain is shown in light blue, and the repeat-rich stalk domain is shown in dark blue.

FIG 3

Structural representations of CdrA. (A) Different domains, including domains predicted from homology modeling, and their locations are indicated schematically (10). (B) A WebLogo summary showing the 14 imperfect repeats of approximately 81 amino acids within CdrA.