Functional bacterial amyloid: the genes that built biofilm?

Speaker: Professor Daniel Otzen, Interdisciplinary Nanoscience Center, AU
Host: Professor Kresten Lindorff-Larsen, Biomolecular Sciences, BIO

Abstract:
Although amyloid is often associated with debilitating diseases such as Alzheimer’s, Huntington’s and Parkinson’s, there is a growing number of examples of beneficial use of amyloid in all walks of life. In the bacterial world alone, a significant proportion of sampled species appears to produce functional bacterial amyloid (FuBA), which may serve multiple purposes such as surface adhesion, biofilm formation, enhanced surface hydrophobicity, extracellular casing or strengthening of the cell wall.

FuBA proteins are generally extremely robust and can resist boiling SDS solutions, though they can still be degraded by proteases. They are evolutionarily optimized to form amyloid structures. As monomers, they assume a random coil structure in solution but show an extremely high propensity to self-assemble and form amyloid under a wide range of conditions. Given this intermolecular attraction, it is important for the cell to develop an efficient manufacturing system that keeps the amyloid proteins soluble until they reach their end station.

Consequently cells have an intricate system to export and assemble FuBA proteins, involving a cohort of ancillary proteins that appear to form an export-and-assembly system in the outer membrane. We have discovered a novel FuBA operon in the widespread bacterial Pseudomonas family that also confers biofilm forming properties to E. coli. This operon consists of the FuBA protein proper (FapC) plus at least 5 additional proteins. FapC in Pseudomonas consists of 3 imperfect repeats separated by linkers of variable lengths which contribute to amyloidogenicity to different extents. FapC homologs in other systems can contain many more units of this repeat. The repeats are critical to amyloid structure: for the E. coli FuBA CsgA, we have computed the structure to consist of a highly conserved β-helix where each turn corresponds to a repeat sequence. Force spectroscopy studies reveal that FuBA promotes biofilm because it is highly hydrophobic and adhesive. Understanding how this modularity in practice regulates amyloid properties holds great potential in the development of smart and robust self-assembled biomaterials.