Amyloids are insoluble fibrous protein aggregates with a beta sheet structure. They have had a lot of bad publicity because they are associated with diseases such as Alzheimer’s, Huntington’s, and the spongiform encephalopathies associated with prions. In these conditions, the deposits of amyloid protein within nerve cells are toxic and lead to the death of cells and consequent neurological symptoms. But recently, we have slowly become aware that amyloids are not necessarily “evil” and that “functional” amyloids contribute to normal cellular biology, being used as structural elements by lower organisms and involved in the production of proteins such as melanin.
So what is it about amyloids – why are they so widespread in living organisms? The amyloid fold which produces the characteristic beta sheet structure of all amyloids is a pre-programmed event, so amyloid polymers can self-assemble without any exogenous energy, inside or outside the cell from which they originate. Once made, amyloid polymers are resistant to harsh conditions that would denature most proteins – a pretty useful characteristic. A new article in PLOS Pathogens looks at the various roles of bacterial amyloids in host, polymicrobial, and environmental interactions and makes some interesting suggestions (Disease to Dirt: The Biology of Microbial Amyloids. (2013) PLoS Pathog 9(11): e1003740. doi:10.1371/journal.ppat.1003740).
Amyloid fibres are common as part of the extracellular matrix that holds biofilms together. It is easy to see how useful amyloid is in this environment. The fibres are produced extracelluarly and reinforce the complex protein and polysaccharide matrix of the biofil that protects the communities of cells it contains. Escherichia coli, Salmonella enterica serovar Typhimurium, Bacillus subtilis, Staphylococcus aureus, Mycobacterium tuberculosis, and many others, all produce extracellular amyloid fibers, as do between 5–40% of species isolated from natural biofilms found in seawater, sludge, and drinking water. Amyloids are very common then, but they do much more than acting as reinforcing rods in the biofilm matrix.
Curli are fibres composed of amyloid found in the complex extracellular matrix produced by many Enterobacteriaceae such as E. coli and Salmonella (Curli biogenesis and function. (2006) Annu Rev Microbiol. 60: 131-47). Curli are involved in adhesion to surfaces, cell aggregation, biofilm formation and mediate host cell adhesion and invasion, and they are potent inducers of the mammalian inflammatory response and plant hypersensitive immune response. This is where it gets interesting because in this context amyloid has moved from being mere structural reinforcement to what is now known as “functional amyloid”. In come cases curli act as adhesins, and in a few cases (such as Klebsiella pneumoniae), as toxins which can trigger apoptosis in human cells.
The reason amyloid has had such as bad press is because the tangled plaques of amyloid fibrils found in conditions such as Alzheimer’s diseases are clearly examples of amyloid formation at the wrong time, in the wrong place or with the wrong constituents. Mature amyloid fibrils do not appear to be inherently toxic if handled appropriately by the cell and essential components of many aspects of cell biology. Finding out more about the normal as opposed to the abnormal biology of amyloid will have great benefits in understanding bacterial growth and pathogenesis. This knowledge could lead to potential therapies or probiotics to designed beneficially exploit amyloid formation in the host and environment or to counteract bacterial cell invasion mechanisms.