Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation

Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated func-tional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm. CO 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecom-mons.org/licenses/by/4.0/).

Automated summary

Functional bacterial amyloid provides structural stability in biofilm, which can be targeted for anti-biofilm therapeutics. Aggregation-modulating peptides can be used to disrupt the stability and morphology of amyloid proteins, such as CsgA and FapC, resulting in reduced biofilm formation in E. coli and P. aeruginosa. This study demonstrates the potential of selective amyloid targeting in combating bacterial biofilm.