Microbial manipulation of the amyloid fold

Abstract

Microbial biofilms are encased in a protein, DNA, and polysaccharide matrix that protects the community, promotes interactions with the environment, and helps cells adhere together. The protein component of these matrices is often a remarkably stable, β-sheet-rich polymer called amyloid. Amyloids form ordered, self-templating fibers that are highly aggregative, making them a valuable biofilm component. Some eukaryotic proteins inappropriately adopt the amyloid fold, and these misfolded protein aggregates disrupt normal cellular proteostasis, which can cause significant cytotoxicity. Indeed, until recently amyloids were considered solely the result of protein misfolding. However, research over the past decade has revealed how various organisms have capitalized on the amyloid fold by developing sophisticated biogenesis pathways that coordinate gene expression, protein folding, and secretion so that amyloid-related toxicities are minimized. How microbes manipulate amyloids, by augmenting their advantageous properties and by reducing their undesirable properties, will be the subject of this review.

Figure 1

General schematic for how amyloids form. Unfolded monomers form intermediate oligomers, some of which are toxic, during the lag phase of amyloid assembly. Once the on-pathway oligomers, or seeds, have formed rapid fiber assembly ensues. The lag phase can be bypassed by addition of pre-formed seeds to monomers.

Figure 2

Structure-function dynamics of Staphylococcal phenol-soluble modulins (PSMs). Soluble PSMs are able to mediate S. aureus biofilm disassembly, to recruit and activate neutrophils, and to lyse neutrophils and niche bacteria such as group A Streptococcus. Once polymerized, PSMs lose the ability to disrupt S. aureus biofilms. Fibrous PSMs stabilize biofilms and confer resistance to proteinase K, dispersin B, and DNase I.

Figure 3

Secretion/polymerization curli fiber assembly. (A) WT E. coli secretes soluble CsgA proteins into the extracellular milieu. Once outside the cell, CsgA encounters surface-attached CsgB seeds that nucleate CsgA amyloid formation. (B) Transmission electron microscopy (TEM) image of curliated E. coli. (C) Inter-bacterial complementation between a CsgA expressing E. coli csgB mutant and a CsgB expressing S. typhimurium csgA mutant. E. coli secretes monomeric CsgA that can interact with CsgB nucleators on the surface of S. typhimurium. (D) TEM images of an E. coli csgB mutant, a S. typhimurium csgA mutant (producing flagella), and a mixed culture biofilm where curli fibers can be seen.