Small molecule disruption of B. subtilis biofilms by targeting the amyloid matrix

Abstract

Small molecule inhibitors of amyloid aggregation have potential as treatment for a variety of conditions. In this issue of Chemistry & Biology, Romero and colleagues use amyloid-dependent B. subtilis biofilm formation to screen for amyloid inhibitors, identifying compounds that not only inhibit B. subtilis biofilm formation but also ones that disrupt preformed biofilms.

Fig. 1. Various modes of action of amyloid modulatory molecules

a. A typical amyloid pathway. During the rate-limiting, lag phase, unfolded monomeric proteins assemble into conformationally dynamic oligomers. These oligomers can serve as seeds or templates that guide mature amyloid formation. b. Inhibition at the monomer stage, the protein does not proceed to the oligomer intermediate. c. A molecule capable of disassembling preformed amyloid fibers. d. Stimulation of amyloid formation.